Title of Invention	"A N-6 SUBSTITUTED 7-DEAZAPURINE"
Abstract	wherein N, R1 and R2 together form wherein m is 0, 1, 2, or 3; RA and RB are each independently be H, -OH, -CH2OH, -CHzCH3OH, -C(=0)NH2, a heteroatom, or -C (=O)NRuR11' ; wherein RS3 is aryl, substituted aryl, or heteroaryi; wherein Ku' is alkyl, or XR11", wherein X is 0, or N and Ru" is substituted alkyl or aryl;

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COMPODKDS SPECIFIC TO ADENOSINE A1, A2A, AND A2, RECEPTOR AND USES THEREOF This applicacion is a continuation-in-part and claims priority of U.S. Serial Nos. 09/454,074,filed December 2, 1999, 09/454,254, filed December 2, 1999, and 09/454,075, December 2, 1999, each of which are hereby incorporated by reference in its entirety. Throughout this applicaticn, reference is made to compounds chat specifically bina to i) adenosine Alf receptors, (such as inter alia, pages 4-76, 130-175, and 257-287,) ii) adenosine A2, receptors (such as inter alia, pages 176-201, and pages 288-293), and adenosine A3 receptors (such as inter alia, pages 202-256, and 294-300). Background of Che Inventlon Adenosine is an ubiquitous modulator of numerous physiological activities, particularly within the cardiovascular and nervous systems. The effects of adenosine appear to be mediated by specific cell surface receptor proteins. Adenosine modulates diverse physiological functions including induction of sedation, vasodilation, auppreasion of cardiac rate and contractility, inhibition of platelet aggregability, stimulation of gluconeogenesis and inhibition of lipolys.is. In addition to its effects on adenylate cyclase, adenosine has been shown to open potassium channels, reduce flux through calcium channels, and inhibit or stimulate phosphoinositide turnover through receptor-mediated mechanisms (See for example, C.E. Muller and B. Stein "Adenosine Receptor Antagonists: Structures and Potenţial Therapeutic Applications," Current Pharmaceutical Design, 2:501 (1996) and C.E. Muller "Aj-Adenosine Receptor Antagonists," Exp. Opin. Thsr. Patents 7(5):419 (1997)).Adenosine receptors belong to the superfamily of purine receptors which are currently subdivided into P: (adenosine) and ?2 (ATP, ADP, and other nucleotides) receptors. Four receptor subtypes for the nucleoside adenosine have been cloned so far f rom various species including humans. Two receptor subtypes (Ai and A2a) exhibit affinity for adenosine in the nanomolar range while two other known subtypes A2b and A3 are low-affinity receptors, with affinity for adenosine in the low-micromolar range. A! and A3 adenosine receptor activation can lead to an inhibition of adenylate cyclase activity, while A2a and A2b activation causes a stimulation of adenylate cyclase. A few AX antagonists have been developed for the treatment of cognitive disease, renal failure, and cardiac arrhythmias. It has been suggested that A2a antagonists may be beneficial for patients suffering f rom Morbus Parkinson (Parkinson's disease) . Particularly in view of the potenţial for local delivery, adenosine receptor antagonists may be valuable for treatment of allergic inflammation and asthma. Available information (for example, Nyce & Metzger "DNA antisense Therapy for Asthma in an Animal Model" Nature (1997) 385: 721-5) indicates that in this pathophysiologic context, A, antagonists may block contraction of smooth muscle underlying respiratory epithelia, while A2& or A3 receptor antagonists may block mast cell degranulation, mitigating the release of histamine and other inf lammatory mediators. A:s receptors have been discovered throughout the gastrointestinal tract, especially in the colon and the intestinal epithelia. It has been suggested that A,b receptors mediate cAMP response (Strohmeier et al., J. Bio. Chem. (1995) 270:2387-94). Adenosine receptors have also been shown to exist on the retinas of various mammalian species including bovine, porcine, monkey, rât, guinea pig, mouse, rabbit and human (See, Blazynski et al., Discrete Distributions of Adenosine Receptors in Maimalian Retina, Journal of Neurochsmistry, volume 54, pages 648-655 (1990); Woods et al., Characterization of Adenosine A2-Receptor Binding Sites in Bovine Retinal Afembranes, Experimental Eye Research, volume 53, pages 325-331 (1991); and Braas et al., Endogenous adenosine and adenosine receptors localized to ganglion cella of the retina, Proceedings of the National Academy of Science, volume 84, pages 3906-3910 (1987)). Recently, Williams reported the observation of adenosine transport sites in a cultured human retinal cell line (Williams et al., Nucleoside Transport Sites in a Cultured Human Retinal Cell Line Established By SV-40 T Antigen Gene, Current Eye Research, volume 13, pages 109-118 (1994)). Compounds which regulate the uptake of adenosine uptake have previously been suggested as potenţial therapeutic agents for the treatment of retinal and optic nerve head damage. In U.S. Patent No. 5,780,450 to Shade, Shade discusses the use of adenosine uptake inhibitors for treating eye disorders. Shade does not disclose the use of specific A3 receptor inhibitors. The entire contents of U.S. Patent No. 5,780,450 are hereby incorporated herein by reference. Additional adenosine receptor antagbnists are needed as pharmacological tools and are of considerable interest as drugs for the above-referenced disease states and/or condiţiona. Invenţia The present invention is basec on compounds which seiectivelv bind to adenosine A: receptor, chereby treating a disease associaced with Ai adenosine receptor in a subject by administering to the subject a therapeuticaily effective amount of such compounds. The disease to be treated are associated with cognitive disease, renal failure, cardiac arrhytihmias, respiratory epithelia, transmit ter release, sedat ion, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstrict ion, neutropil chemotaxis, reflux condition, or ulcerat ive condition. The present invention is based, at least in part, on the discovery that certain N-6 substituted 7-deazapurines, described infra, can be used to treat a N-6 substituted 7-deazapurine responsive state. Examples of such states include those in which the activity of the adenosine receptors is increased, e. g., bronchitis, gastrointestinal disorders, or asthma. These states can be characterized in that adenosine receptor activation can lead to the inhibition or stimulation of adenylate cyclase activity. Compositions and methods of the invention include enantiomerically or diastereomerically pure N-6 substituted 7-deazapurines . Preferred N-6 substituted 7-deazapurines include those which have an acetamide, carboxamide, substituted cyclohexyl, e. g., cyclohexanol, or a urea moiety attached to the N-6 nitrogen through an alkylene chain. The presenc invention pertains to methods for modulating an adenosine receptor (s) in a mammal by administering to the mammal a therapeuticaily effective amount of a N-6 substituted 7-deazapurine, such that modulation of the adenosine receptor 's activity occurs . Suitable adenosine receptors include the families of AJ, A2, or A3 In a preferred embodiment, the N-6 substituted 7-deazapurine is a adenosine receptor antagonist. The invention further pertains to methods for treating N-6 substituted 7-deazapurine disorders, e.g., asthma, bronchitis, allergic rhinitis, chronic obstructive pulmonary disease, renal disorders, gastrointestinal disorders, and eye disorders, in a mammal by administering to the mammal a therapeutically effective amount of a N-6 substituted 7-deazapurine, such that treatment of the disorder in the mammal occurs. Sui table N-6 substituted 7 deazapurines include those illustrated by the general formula I : (Figure Removed) and pharmaceutically acceptable salts thereof. R! and R2 are each independently a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety or together fortn a substituted or unsubstituted heterocyclic ring. R3 is a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. R4 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. Rş and Rg are each independently a halogen atom, e.g., chlorine, fluorine, or bromine, a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety, or RS is carboxyl, esters of carboxyl, or carboxamides, or R4 and R$ or R*, and Rg together form a substituted or unsubstituted heterocyclic or carbocyclic ring. In certain embodiments, R ţ and R2 can each indepehdently be a substituted or unsubstituted cycloalkyl or heteroarylalkyl moieties. In other embodiments, R3 is a hydrogen atom or a substituted or unsubstituted heteroaryl moiety. In still other embodiments, R, R= and R£ can each be independentIy = heteroaryl moieties. In a preferred embodiment, R- îs a hydrogen atom, R2 is a cyclohexanol, e. g., rrzr.s- cyclohexanol, R3 is phenyl, R is a hydrogen atoir., Rţ îs a methyl group and Rg is a methyl group. In st iii another embodiment, Rj is a hydrogen atom, R2 is (Figure Removed) t R3 is phenyl, R4 is a hydrogen atom and R5 and R6 are methyl groups. The invention further pertains to pharmaceutical compositions for treating a N-6 substituted 7-deazapurine responsive state in a mammal, e.g., asthma, bronchitis, allergic rhinitis, chronic obstructive pulmonary disease, renal disorders, gastrointestinal disorders, and eye disorders. The pharmaceutical composition includes a therapeutically effective amount of a N-6 substituted 7-deazapurine and a pharmaceutically acceptable carrier. The present invention also pertains to packaged pharmaceutical compositions for treating a N-6 substituted 7-deazapurine responsive state in a mammal. The packaged pharmaceutical composition includes a container holding a therapeutically effective amount of at least one N-6 substituted 7-deazapurine and instructions for using the N-6 substituted 7-deazapurine for treating a N-6 substituted 7-deazapurine responsive state in a mammal. The invention further pertains co compounds of fermula : wherein R! is hydrogen; R2 is subscicuted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, or R i and R2 together form a substirutec or unsubstituted heterocyclic ring; R3 is unsubstituted or substituted aryl; R 4 is hydrogen; and R5 and Rg are each independent ly hydrogen or alkyl, and pharmaceutically acceptable salts thereof. The deazapurines of this embodiment may advantageously be selective A:. receptor antagonista. These compounds may be useful for numerous therapeutic uses such as, for example, the treatment of asthma, kidney failure associated with heart failure, and glaucoma. In a particularly preferred embodiment, the deazapurine is a water soluble prodrug that is capable of being metabolized in vivo to an active drug by, for example, esterase catalyzed hydrolysis. In yet another embodiment, the invention features a method for inhibiting the activity of an adenosine receptor (e.g., A2) in a cell, by contacting the cell with N-6 substituted 7-deazapurine (e.g., preferably, an adenosine receptor antagonist). In another aspect, the invention features a method for treating damage to the eye of an .animal (e.g., a human) by administering to the animal an effective amount of an N-6 substituted 7-deazapurine of formula I. Preferably, the N-6 substituted 7-deazapurine is an antagonist of A, adenosine receptors in cells of the animal. The damage is to the retina or the optic nerve head and may be acute or chronic. The damage may be the result of, for example, glaucoma, edema, ischemia, hypoxia or trauma. The invention also features a pharmaceutical composition cotnprising a N-6 substituted compound of formula I. Preferably, the pharmaceutical preparation is an ophthalmic formulation (e.g., an periocular, retrobulbar or intraocular injection formulation, a systemic formulation, or a surgical irrigating solution). In yet another embodiment, the invention features a compound having the formula II: (Figure Removed) wherein X is N or CR6; Rj and R2 are each independently hydrogen, or substituted or unsubstituted alkoxy, aminoalkyl, alkyl, aryl, or alkylaryl, or together form a substituted or unsubstituted heterocyclic ring, provided that both Rj and R2 are'both not hydrogen; R3 is substituted or unsubstituted alkyl, arylalkyl, or aryl; R4 is hydrogen or substituted or unsubstituted C:- Cg alkyl; L is hydrogen, substituted or unsubstituted alkyl, or R4 and L together form a substituted or unsubstituted heterocyclic or carbocyclic ring,- R6 is hydrogen, substituted or unsubstituted alkyl, or halogen; Q is CH2, O, S, or NR7, wherein R7 is hydrogen or substituted or unsubstituted Cx- C6 alkyl; and W is unsubstituted or substituted alkyl, cycloalkyl, aryl, arylalkyl, biaryl, heteroaryl, substituted carbonyl, substituted thiocarbonyl, or substituted sulfonyl; provided t ha t if R; is pyrrolidinc, ther. R, îs r.rz methyl. The invenţie:: aiso perrains to pharmaceuricallv acceptable salts and prodrugs of rhe cotspour.ds cf rr.e invention. In an advantageous embodiment, X is CRt- and C is CH:. O, S, or NK in formula II, wherein R^ is as defined above. In anorher embodimsnt of formula II, X is N. The invention furrher pertains to a merhod for inhiriring rhe acriviry of an adenosine receptor (e.g., an A:.. adenosine receptor) in a cell by contacting the cell with a compound of the invention. Preferably, the compound is an antagonist of the receptor. The invention also pertains to a method for treating a gastrointestinal disorder (e.g., diarrhea) or a respiratory disorder (e.g., allergic rhinitis, chronic obstructive pulmonary disease) ir. an animal by administering to an animal an effective amount of a compound of formula II (e.g., an antagonist of A;r) . Preferably, the animal is a human. This invention also features a compound having the structure: (Figure Removed) wherain R: is crans-4-hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, 2-methylamino carbonylami.no cyclohexyl, acetamido ethyl, or methylamino carbonylamino ethyl; wherein R3 is a substituted or unsubstituted four to six membered ring. +r wherein R5 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R7) (R8) XR9 wherein X is O, S, or NR10, wherein R7 and R8 are each independently H or alkyl, wherein R9 and R10 are each independently alkyl or cycloalkyl, or R9 and R10 and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members; wherein R6 is H, alkyl, substituted alkyl, cycloalkyl; or a pharmaceutically acceptable salt, or a prodrug derivative, or a biologically active metabolite; with the proviso that when R1 is acetylamino ethyl, R3 is not 4-pyridyl. In one emcoaimenc or cne compounc, #3 îs pneny_, pyrrc^e, thiophene, furan, chiazole, imidazole, pyrazcle, 1.2.4- criazole, pyridine, 2 (1H)-pyridone, 4(1K)-pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazcle, terrazole, naphthalene, terralin, naphthyridine, benzofuran, benzcthiophene, indole, 2,3-dihydroindcle, IH-indcie, indoline, benzopyrazole, l,3-benzodioxole, benzoxazcie, purine, coumarin, chrornone, guinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido[2.3- b]pyrazine, pyr ido [3, 4 -b] pyrazine, pyrido [3 , 2-c] pyridazine , purido [3,4-b]-pyridine, IH-pyrazole[3 , 4-d] pyrimidine, pteridine, 2 (1H)-quinolone, l(2H)-isoquinolone, 1.4- benzisoxazine, benzothiazole, quinoxaline, guinoline-N-oxide. isoguinoline-N-oxide, quinoxaline-N-oxide, guinazoline-N- oxide. benzoxazine, phthalazine, cinnoline, or having a structure: (Figure Removed) wherein Y is carbon or nitrogen; wherein R. and R' are independencly H, substituced or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, methoxy, methyl amino, or methyl thio This invention also pertains to a compound having the structure .- wherein -Rt- is aryl, substituted aryl, or heteroaryl; wherein -&r is H, . alkyl, substituted alkyl, or cycloalkyl; wherein -Rr is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(-Rr) (-R-) NR*ft?'.° wherein W and -R»-are each H or alkyl, wherein-R*-'and -Rs-'°are each alkyl or cycloalkyl, or R«-, -fe-' and the nitrogen together forrn a ring system of between 4 and 7 members. This invention also features a method for inhibiting the an activity of adenosine receptor in a cell, which comprises contacting said cell with the above-tnentioned compounds. Deserition The features and other details of the inventior. will r.ow 05 more particularly described and pointed our ir. the clairr.s. It will bc understood that the particular embocimer.rs of the invention are shown by way of illustratior. and nor as limitations of che invention. The principie fearures of this invention can be employed in various embodimer.zs without departing f rom the scope of the invention. The present invention pertains to methods for treating a N- 6 substituted 7-deazapurine responsive state in a mammal . The methods include administrat ion of a therapeuticaliy effective amount of a N-6 substituted 7-deazapurine, described infra, to the mammal, such that treatment of the N-6 substituted 7-deazapurine responsive state in the mammal occurs. The language "N-6 substituted 7-deazapurine responsive state" is intended to include a disease state or condition characterized by its responsiveness to treatment with a N-6 substituted 7-deazapurine of the invention as described infra, e. g., the treatment includes a significant diminishment of at least one symptom or effect of the state achieved with a N-6 substituted 7-deazapurine of the invention. Typically such states are associated with an increase of adenosine within a host such that the host often experiences physiological symptoms which include, but are not limited to, release of toxins, inf lammation, coma, water retention, weight gain or weight loss, pancreatitis, ernphysema, rheumatoid arthritis, osteoarthritis, multiple organ failure, infant and adult respiratory distress syndrome, allergic rhinitis, chronic obstructive pulmonary disease, eye disorders, gastrointestinal disorders, skin tumor promotion, immunodef iciency and asthma. (See for example, C. E. Muller and B. Stein "Adenosine Receptor Antagonists: Structures and Potenţial Therapeutic Applications," Current PharmaceutjicaJ Design, 2:501 (1996) and C. E. Muller "Adenosine Receptor Antagonists , " Exp. Opiu. Tber. Pacenrs 7(5):419 (1997) and I. Feoktistove, R. Polosa, S. T. Hoigate and I. Biaggioni "Ader.osir.e A--recepcors: a novei cherapeuric rarget in aschina?" 19; 148 (1998)). The effects often associated with such syrr.pcoins include, but are not limited co, fever, shortness of breath, nausea, diarrhea, weakness, headache, and even dearh. Ir. one embodiment, a N-6 substituted 7-deazapurine responsive state includes those disease states which are mediatec by stimulation of adenosine receptors, e.g., A1, A2a, &2b antagonist. Examples of suitable responsive states which can be treated by the compounds of the invention, e.g., adenosine receptor subtypes which mediate biological effects, include central nervous system (CNS) effects, cardiovascular effects, renal effects, respiratory effects, immunological effects, gastro-intestinal effects and metabolic effects. The relative amount of adenosine in a subject can be associated with the effects listed below; that is increased levels of adenosine can trigger an effect, e.g., an undesired physiological response, e.g., an asthmatic attack. CNS effects include decreased transmitter release (Aj) , sedation (Aa) , decreased locomotor activity (A2j) , anticonvulsant activity, chemoreceptor stimulation (A2) and hyperalgesia. Therapeutic applications of the inventive compounds include treatment of dementia, Alzheimer's disease and memory enhancement. Cardiovascular effects include vasodilation (A2a), (A2b) and (A3) , vasoconstriction (A:) , bradycardia (Aj), platelet inhibition (A2a) , negative cardiac inotropy and dromotropy (Aj), arrhythmia, tachycardia and angiogenesis. Therapeutic applications of the inventive compounds include, fer exarr.pie, prevention of ischaemia-inducea impairment of the heart ar.d cardiotonics, myocardial cissue proteccion and restoratior. of cardiac function. Renal effects include decreased GFR (A:) , mesangial cell contraction (A:) , ancidiuresis (Ax) and inhibiticr. cf renin release (Aa) . Suitable therapeutic applicatior.s of the inventive compounds include usc of the inventive compounds as diuretic, natriuretic, potassium-sparing, kidney-protective/prevention of acute renal failure, antihypertensive, anti-oedematous and anti-nephriric agents. Respiratory effects include bronchodilation (A2) , bronchoconstriction (Aj), chronic obstructive pulmonary disease, allergic rhinitis, mucus secretion and respiratory depression (A2). Suitable therapeutic applications for the compounds of the invention include anti-asthmatic applications, treatment of lung disease after transplantation and respiratory disorders. Immunological effects include immunosuppression (A2) , neutrophil chemotaxis (Ax), neutrophil superoxide generation (A2a) and mast cell degranulation (A2b and A3) Therapeutic applications of antagonists include allergic and non allergic inflammation, e.g., release of histamine and other inflammatory mediators. Gastrointestinal effects include inhibition of acid secretion (Aj) therapeutic application may include reflux and ulcerative conditions Gastrointestinal effects also include colonie, intestinal and diarrheal disease, e.g., diarrheal disease associated with intestinal inflammation (A2D) . Eye disorders include retinal and optic nerve head injury and trauma related disorders (A,) . In a preferred embodiment, the eye disorder is glaucoma. Other therapeutic applicatior.s of the compounds cf zhs invention include treatment cf obesity (lipclyt:.c properries) , hypertension, treatment cf depressior., sedative, anxiolytic, as antileptics and as laxatives, e.ş., effectinc motility without causing diarrhea. The term "disease state" is intended to include those conditions caused by or associated with unwanted levels of adenosine, adenylyl cyclase activity, increased physiological activity associated with aberrant stimulation of adenosine receptors and/or an increase in cAMP. In one embodiment, the disease state is, for example, asthtna, chronic obstructive pulmonary disease, allergic rhinitis, bronchitis, renal disorders, gastrointestinal disorders, or eye disorders. Additional examples include chronic bronchitis and cystic fibrosis. Suitable examples of inflammatory diseases include non-lymphocytic leukemia, myocardial ischaemia, angina, infarction, cerebrovascular ischaemia, interraittent claudication, criticai limb ischemia, venous hypertension, varicose veins, venous ulceration and arteriosclerosis. Impaired reperfusion states include, for example, any post-surgical trauma, such as reconstructive surgery, thrombolysis or angioplasty. The language "treatment of a N-6 substituted 7-deazapurine responsive state" or "treating a N-6 substituted 7-deazapurine responsive state" is intended to include changes in a disease state or condition, as described above, such that physiological symptoms in a mammal can be significantly diminished or minimized. The language also includes control, prevention or inhibition of physiological symptoms or effects associated with an aberrant amount of adenosine. In one preferred embodiment, the control of the disease state or condition is such that the disease state or condition is eradicated. In another preferred embodiment, the control is selective such that aberrant levels of adenosine receptor activity are controlled while other physiologic systems and parameters are unaffected. The term "N-6 suostitutec 7-aeazapurine" is ari reccrr.zi and is intended to include those compounds having rhe fcrr.uJ (Figure Removed) N-substituted 7-deazapurine" includes pharmaceutically acceptable salcs thereof, and, in one embodiment, also includes certain N-6 substituted purines described herein. In cerrain embodimencs, che N-€ substituted 7-deazapurine is not N-6 benzyl or N-6 phenylethyl substituted. In other embodiments, R4 is not benzyl or phenylethyl substituted. In preferred embodiments, R± and R2 are both not hydrogen atoras. R3 i s not a hydrogen In still other preferred embodiments, atom. The language "therapeutically effective amount" of an N-6 substituted 7-deazapurine, described infra, is that amount of a therapeutic compound necessary or sufficient to perform its intended function within a mammal, e.g., treat a N-€ substituted 7-deazapurine responsive state, or a disease state in a mammal. An effective amount of the therapeutic compound can vary according to factors such as the amount of the causative agent already present in the mammal, the age, sex, and weight of the mammal, and the ability of the therapeutic compounds of the present invention to affect a N-6 substituted 7-deazapurine responsive state in the mammal. One of orcinary skill in che arc would be able ce scudy che aforementioned faccors and make a decerminacior. regarding che effeccive amounc of che rherapeucic compound wichouc undue experimencation. An in vicro or in vivc assay alsc car. be used to determine an "effective amounc" of che cherapeucic compounds described infra. . The ordinarily skiiied arcisar. would selecc an appropriace amounc of che cherapeucic compound for use in che aforemencioned assay or as a cherapeucic creacmenc. A cherapeucically effeccive amounc preferably diminishes ac leasc one sympcom or effecc associaced wich che N-6 subscicuced 7-deazapurine responsive scace or condicion being creaced by ac leasc abouC 20%, (more preferably by ac leasc abouc 40%, even more preferably by ac leasc abouc 60%, and scill more preferably by ac leasc abouc 80%) relacive co uncreaced subjeccs. Assays can be designed by one skilled in che arc co measure che diminishmenc of such sympcoms and/or effeccs. Any arc recognized assay capable of measuring such paramecers are incended co be included as parc of this invencion. For example, if aschma is che scace being creaced, chen che volume of air expended f rom Che lungs of a subjecc can be measured before and afcer creacmenc for measuremenc of increase in che volume using an arc recognized cechnique. Likewise, if inflammacion is che scace being creaced, chen che area which is inflamed can be measured before and afcer creacmenc for measuremenc of diminishmenc in che area inflamed using an arc recognized cechnique. The cerm "cell" includes boch prokaryocic .and eukaryocic cells. The Cerm "animal" includes any organism with adenosine recepcors or any organism suscepcible co a N-6-subscicuced 7-deazapurine responsive scace. Examples of animals include yeasc, mammals, repciles, and birds. ic also includes cransgenic animals. The tertn "mammal" is art recognized and is ir.rer.dec re include an animal, more preferably a warm-biooâed ar.inial, most preferably căţele, sheep, pigs, horses, dogs, cazs, rât s, mice, and humans. Mammals susceptibie te a K-6 substituted 7-deazapurine responsive state, ir.fiammatior., emphysema, asthma, central nervous system conditions, cr acute respiratory distress syndrome, for exampie, are included as part of this invention. In another aspect, the present invention pertains to methods for raodulating an adenosine receptor(s) in a mammal by administering to the mammal a therapeutically effective amount of a N-6 substituted 7-deazapurine, such that modulation of the adenosine receptor in the mammal occurs. Suitable adenosine receptors include the families of A,, A2, or A3- In a preferred embodiment, the N-6 substituted 7-deazapurine is an adenosine receptor antagonist. The language "modulating an adenosine receptor" is intended to include those instances where a compound interacts with an adenosine receptor(s), causing increased, decreased or abnormal physiological activity associated with an adenosine receptor or subseguent cascade effects resulting from the modulation of the adenosine receptor. Physiological' activities associated with adenosine receptors include induction of sedation, vasodilation, suppression of cardiac rate and contractility, inhibition of platelet aggregbility, stimulation of gluconeogenesis, inhibition of lipolysis, opening of potassium channels, reducing flux of calcium channels, etc. The terms "modulate", "modulating" and "modulation" are intended to include preventing, eradicating, or inhibiting the resulting increase of undesired physiological activity associated with abnormal stimulation of an adenosine receptor, e.g., in the context of the therapeutic methods of the invention. In another embodiment, the cerm modulate incluaes antagoniscic eneccs, e.g., cimir.ishmsr.r of the activicy or production of mediators of allergy and allergdc inflammation which results from the overstimulaticn c: adenosine recepcor(s) . For example, the therapeutic deazapurines of che invention car. interact with ar. adsr.osine receptor co inhibit, for example, adenylate cyclase activity. The language "condition characterized by aberrant adenosine receptor activity" is incended to include chose diseases, disorders or conditions which are associated with aberrant scimulation of an adenosine receptor, in that the stimuiatior. of the receptor causes a biochemical and or physiological chain of events that is directly or indirectly associated with the disease, disorder or condition. This scimulation of an adenosine receptor does not have to be the sole causative agent of the disease, disorder or condition but merely be responsible for causing some of the symptoms typically associated with the disease, disorder, or condition being treated. The aberrant stimulation of the receptor can be the sole factor or at least one other agent can be involved in the state being treated. Exaraples of conditions include those disease states listed supra, including inflammation, gastrointestinal disorders and those symptoms manifested by t-he presence of increased adenosine receptor activity. Preferred examples include those symptoms associated with asthma, allergic rhinitis, chronic obstructive pulmonary disease, emphyserna, bronchitis, gastrointestinal disorders and glaucotna. The language "treating or treatment of a condition characterized by aberrant adenosine receptor activity" is intended to include the alleviation of or diminishment of at least one symptom typically associated with the condition. The treatment also includes alleviation or diminishment of more than one symptom. Preferably, the treatment cures, e.g., substantially eliminates, the symptoms associated with the condition. The present invention pertains to compounds, N-c 7-deazapurines, having che formula I: (Figure Removed) whersin R} and Rj are each independent ly a hydrogen atom or a substicuted or unsubstituted alkyl, aryl, or alkylaryl tnoiety or together form a substituted or unsubstituted heterocyclic ring; R3 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety; R4 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. R$ and Rg are each independently a halogen atom, e. g., chlorine, fluorine, or bromine, a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety or R4 and R5 or R5 and Rg together form a substituted or unsubstituted heterocyclic or carbocyclic ring. Also included, are pharmaceutically acceptable salts of the N-6 substituted 7-deazapurines. In certain embodiments, R ţ and R2 can each independently be a substituted or unsubstituted cycloalkyl or heteroarylalkyl moieties. In other embodiments, R3 is a hydrogen atom or a substituted or unsubstituted heteroaryl moiety. In still other embodiments, R4, Re, and Rg can each be independently a heteroaryl moiety. In one embodiment, Rj is a hydrogen atom, R2 is a substituted or unsubstituted cyclohexane, cyclopentyl, cyclobutyl or cyclopropane moiecy, R3 is a substituted or uizsubsziru'sd phenyi tnoiety, R4 is a hydrogen atom and R = and R^ are cczr. methyl groups. In another embodiment , R2 is a cyclohexanoi, a cyclohexanediol, a cyclohexylsulf onamide, a cy-iohaxanarr.idc, a cyclohexylester, a cyclohexene, a cyclopenranol or a cyclopentanediol and R3 is a phenyi moiecy. In still anothsr embodiment, Rj is a hydrogen atom, R2 is a cyclohexanoi, R3 is a substituted or unsubstituted phenyi, pyridine, furan, cyclopentane, or thiophene moiety, R4 is a hydrogen atom, a substituted alkyl, aryl or arylalkyl moiety, and Re and R6 are each independently a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, cr alkylaryl moiety. In yet another embodiment, R^ is a hydrogen atom, R2 is substituted or unsubstituted alkylamine, arylamine, or alkyl aryl amine, a substituted or unsubstituted alkylamide, arylamide or alkylarylamide, a substituted or unsubstituted alkylsulf onamide, aryl sul f onamide or alkylarylsulfonamide, a substituted or unsubstituted alkylurea, arylurea or alkylarylurea, a substituted or unsubstituted alkylcarbamate, arylcarbamate or alkylarylcarbamate, a substituted or unsubstituted alkylcarboxylic acid, arylcarboxylic acid or alkylarylcarboxylic acid, R3 is a substituted or unsubstituted phenyi moiety, R4 is a hydrogen atom and R5 and R6 are methyl groups. In still another embodiment, R2 is guanidine, a modified guanidine, cyanoguanidine , a thiourea, a thioamide or an amidine . In one embodiment , R can be (Figure Removed) herein R2a"R2c are -ac'n independently a hydroger. atom cr a saturated or unsacuraced alkyl, aryl cr alkylaryl moiery and R2cj is a hydrogen atom or a saturated or unsaturated alkyl, aryl, or alkylaryl moiety, NR2eR2f' or OR23- wnereir. R2e"K: = are each independently a hydrogen atom or a saruratec cr unsaturated alkyl, aryl or alkylaryl moiecies. Altematively, R2a and R2^ cogecher can form a carbocyclic or heterocyclic ring aaving a ring size between about 3 and S members, e.g., cyclopropyl, cyclopentyl, cyclohexyl groups. In one aspect of the invention, both R5 and R6 are not methyl groups, preferably, one of RS and R6 is an alkyl group, e.g., a methyl group, and the other is a hydrogen atom. In another aspect of the invention, when R4 is 1-phenylethyl and R j is a hydrogen atom, then Rj is not phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3-methoxyphenyl or 4-methoxyphenyl or when R4 and RI are l-phenylethyl, then R3 is not a hydrogen atom or when R4 is a. hydrogen atom and R3 is a phenyl, then R^ is not phenylethyl. In another aspect of the invention, when R5 and R6 together form a carbocyclic ring, e.g., (Figure Removed) or pyrimido[4,5-6]indole, then R3 is not phenyl when R4 is 1-(4-methylphenyl)ethyl, phenylisopropyl, phenyl or 1-phenylethyl or when R3 is not a hydrogen atom when R4 is 1-phenylethyl. The carbocyclic ring formed by Rj and Rg can be either aromatic or aliphatic and can have between 4 and 12 carbon atoms, e.g., naphthyl, phenylcyclohexyl, etc.. preferably becween 5 ane 7 carbon acoms, e.g., cyclcper.ryl cr cyclohexyl. Alcernacively, R5 and R^ cogecher car. fcrrr. a hecerocyclic ring, such as those disclcsec beiow. Typical heterocvclic rings include becween 4 and 12 carbon acoms, preferably becween 5 and 7 carbon acoms, and car. be eicher aromacic or aliphacic. The hecerocyclic ring car. be furcher subscicuced, including subscicucion of one or mere carbon acoms of che ring scruccure wich one or mare heceroacoms. In scill anocher aspecc of che invencion, Ri and K- form a hecerocyclic ring. Represencacive examples include, buc are noc limiced to, chose hecerocyclic rings lisced below, such as morpholino, piperazine and Che like, e.g., 4- hydroxypiperidines, 4-aminopiperidines. Where Ri and R 2 cogecher form a piperazino group, (Figure Removed) wherein R7 can be a hydrogen acom or a subscicuced or unsubscicuced alkyl, aryl or alkylaryl moiecy. In yec anocher aspecc of che invencion R4 and R5 cogecher can form a hecerocyclic ring, e.g., (Figure Removed) wherein che hecerocyclic ring can be eicher aromacic or aliphacic and can form a ring having becween 4 and 12 carbon acoms, e.g., naphchyl, phenylcyclohexyl, ecc. and can be eicher aromacic or aliphacic, e.g., cyclohexyl, cyclopencyl. Tiis neterocyclic ring can be further substituted, inciudir.g substitut ion of carbon atoms of the ring structure with cr.e or more hetcroatoms. Altematively, R^ and R; together car. form a heterocyclic ring, such as those ciisclosed beiow. In certain etnbodiments, the N-6 substituted 7-deazapurine is not N-6 benzyl or N-6 phenylethyl substituted. In other embodiments, R4 is not benzyl or phenylethyl substituted. In preferred embodiments, R} and R£ are both not hydrogen atoms. In still other preferred embodiments, R3 is not K. The compounds of the invention tnay comprise water-soluble prodrugs which are described in WO 99/33815, International Application No. PCT/US98/04595, filed March 9, 1998 and published July B, 1999. The entire content of WO 99/33815 is expressly incorporated herein by reference. The water-soluble prodrugs are metabolized in vivo to an active drug, e.g., by esterase catalyzed hydrolysis. Examples of potenţial prodrugs include deazapurines with, for example, R2 as cycloalkyl substituted with -OC(0)(Z)NH2' wherein Z is a side chain of a naturally or unnaturally occurring amino acid, or analog thereof, an a, 3, Y, or a) amino acids, or a dipeptide. Preferred amino acid side chains include those of glycine, alanine, valine, leucine, isoleucine, lysine, a-methylalanine, aminocyclopropane carboxylic acid, azetidine-2-carboxylic acid, &-alanine, y-aminobutyric acid, alanine-alanine, or glycine-alanine. In a further embodiment, the invention features deazapurines of the formula (I) , wherein RJ is hydrogen; R2 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, or R^ and R2 together form a substituted or unsubstituted heterocyclic ring; R3 is unsubstituted or substituted aryl; R4 is hydrogen; and R5 and R6 are each independently hydrogen or alkyl, and pharmaceutically acceptable salts thereof. The deazapurines of this embodiment may potentially be selective A- receptor antagonists. In one embodiment, R2 is subsritutec ie.ş.. hydroxy substituted) or unsubstituted cycloalkyl. In ar. advar.tageous subembodiment, R i and R4 are hydrogen, R3 îs ur.substiturec cr substituted phenyl, and R5 and Rg are each alkyl. Preferably R2 is mono-hydroxycyc l openty l or mono-hydroxycyciohexyl. R-also may be substituted with -NK-C(=0)E, wherein E is substituted or unsubsticuted C^-C^ alkyl (e.g., alkylamine, e.g-, ethylamine.). R1 and R2 tnay also cogether form a subscituced or unsubsticuted heterocyclic ring, which may be substituted with an amine or acetamido group. In another aspect, R: may be -A-NHC(=0)B, wherein A is unsubstituted C:-C4 alkyl (e.g., ethyl, propyl, butyl), and B is substituted or unsubstituted Cj-C^ alkyl (e.g., methyl, aminoalkyl, e.g., aminomethyl or aminoethyl, alkylamino, e.g., methylamino, ethylamino), preferably when Rj and R4 are hydrogen, R3 is unsubstituted or substituted phenyl, and R5 and Rg are each alkyl. B may be substituted or unsubstituted cycloalkyl, e.g., cyclopropyl or 1-amino-cyclopropyl. In another embodiment, R3 may be substituted or unsubstituted phenyl, preferably when R5 and R6 are each alkyl. Preferably, R2 may have one or more substituents (e.g., o-, m- or p- chlorophenyl, o-, m- or p- fluorophenyl) . Advantageously, R3 may be substituted or unsubstituted heteroaryl, preferably when R$ and Rg are each alkyl. Examples of heteroaryl groups include pyridyl, pyrimidyl, l pyridazinyl, pyrazinyl, pyrrolyl, triazolyl, thioazolyl, oxazolyl, oxadiazolyl, furanyl, methylenedioxyphenyl and thiophenyl. Preferably, R3 is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl or 3 - pyrimidyl. Preferabiy in one embodiment, R= and R- are each hydrcgsr.. In another, R5 and R6 are each methyi. In a particulariy preferred embodiment, the deazapurines c: the invention are water-soluble prodrugs rhat car. be metabolized in vivo to an active drug, e. g. by esterase catalyzed hydrolysis. Preferabiy the prodrug comprises ar. R; group which is cycloalkyl substituted with -OC(0) (Z)NH-., wherein Z is a side chain of a naturally or ur.naturally occurring amino acid, an analog thereof, an a, C-, y, or u amino acid, or a dipeptide. Exaraples of preferred side chains include the side chains of glycine, alanine, valine, leucine, isoleucine, lysine, a-methylalanine, aminocyclopropane carboxylic acid, azetidine-2-carboxylic acid, 6-alanine, Y-aminobutyric acid, alanine-alanine, or glycine-alanine. In a particularly preferred embodiment, 2 is a side chain of glycine, R2 is cyclohexyl, R3 is phenyl, and R5 and Rg are methyi. In another embodiment, the deazapurine is 4-(cis-3-hydroxycyclopentyl) amino-5 , 6-dimethyl-2 -phenyl - 7/f-pyrrolo [2, 3d]pyrimidine. In another embodiment, the deazapurine is 4-(cis-3-(2-aminoacetoxy) cyclopentyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d] pyrimidine trifluoroacetic acid salt. In another embodiment, the deazapurine is 4- (3-acetamido)piperidinyl-5, 6-dimethyl-2-phenyl- 7H-pyrrolo [2, 3d] pyrimidine. In another embodiment, the deazapurine is 4-(2-N'-methylureapropyl)amino-5, 6-dimethyl-2-phenyl - 7H-pyrrolo [2, 3d) pyrimidxne. In another embodimen-, the deazapurine is -i-,2-acetamidobur:yl)aminc-5, 6-dimethyl-2-phenyl-7H-pyrrclc 12.3d! pyrimidine. i In another embodiment, the deazapurine is 4-J2-N'-methylureabutyl) amino-5, 6-dimethyl-2-phenyl- 7H-pyrrcio (2 . 3dj pyrimidine. In another emocdiment, che deazapurine is 4-(2-aminocyclopropylacecamidoethyl) amino-2-phenyl-7H-pyrrolo [2,3d]pyrimidine. In another embodiment, the deazapurine is 4-(crans-4-hydroxycyclohexyl)amino-2-(3-chlorophenyl)-7H-pyrrolo[2,3d] pyrimidine. In another embodiment, the deazapurine is 4-(crans-4-hydroxycyclohexyl)amino-2-(3-fluorophenyl)-7H-pyrrolo[2, 3d] pyrimidine. In another embodiment, the deazapurine is 4-(trans-4-hydroxycyclohexyl)amino-2-(4-pyridyl)-7#-pyrrolo[2,3d] pyrimidine. In yet another embodiment, the invention features a method for inhibiting the activity of an adenosine receptor (e.g., A:, A^, A:B, or, preferably, A3) in a cell, by contacting the cell with N-6 substituted 7-deazapurine (e.g., preferably, an adenosine receptor antagonist). In another aspect, the invention features a method for treating damage to the eye of an animal (e.g., a human) by administering to the animal an effective amount of an N-6 substituted 7-deazapurine. Preferably, the N-6 substituted 7-deazapurine is an antagonist of A; adenosine receptors in cells o* trie animal. The aamage îs to the retina cr the optic nerve head and may fae acute or chronic. The darr.age rriay be the result of, for example, giaucoma, ederaa, ische-ia, hypoxia or trauma. In a preferred embodiment, the invention features a deazapurine having the formula II, supra, wherein X is N or CR6; R! and R- are each independently hydrogen, or substituted or unsubstituted alkoxy, aminoalkyl, alkyl, aryl, or alkylaryl, or together form a substituted or unsubstituted heterocyclic ring, provided that both R! and R: are both not hydrogen; R, is substituted or unsubstituted alkyl, arylalkyl, or aryl; R In one embodiment, in compounds of formula II, X is CR4 and Q is CH2, O, S, or NH. In another embodiment, X is N. In a further embodiment of compounds of formula II, W is substituted or unsubstituted aryl, 5- or 6- member heteroaryl, or biaryl. W may be substituted with one or more substituents. Examples of substituents include: halogen, hydroxy, alkoxy, amino, aminoalkyl, aminocarboxyamide, CN, CF3, C02R8, CONHR8, CONReR9, SOR8, S02Re. and SO2NRgR9, wherein R8 and Ro are each independently hydrogen, or substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. Preferably, W may be substituted or unsubstituted phenyl, e. g., methylenedioxyphenyl. W also may be a substituted or unsubstituted 5-merabered heteroaryl ring, e.c., pyrrcls, pyrazole, oxazole, imidazoie, criazole, tetrazcie, furar., thiophene, thiazole, and oxadiazcle. Preferabiy, K may be a 6-member heteroaryl ring, e.g., pyridyl. pyrimidyl, pyridazinyl, pyrazinal, and thiophenyl. In a preferred emboditnent, W is 2-pyridyl, 3- pyridyl, -î-pyridyl, 2-pyrimidyl, 4-pyrimidyl, or 5-pyrimidyl. In one advantageous embodiment of compounds of formula II, C is NH and W is a 3-pyrazolo ring which is unsubstituted or N-substitutcd by substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In another embodiment of compounds of formula II, O is cxygen, and W is a 2-thiazolo ring which is unsubstituted or substituted by substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In another embodiment of compounds of formula II, W is substituted or unsubstituted alkyl, cycloalkyl e.g., cyclopentyl, or arylalkyl. Examples of substituents include halogen, hydroxy , substituted or unsubstituted alkyl, cycloalkyl, aryl, arylalkyl, or NHR10, wherein R10 is hydrogen, or substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In yet another embodiment, the ' invention features a deazapurine of formula II wherein W is -(CH:) ,-C(-0)Y or - each independently hydrogen, or unsubstituted or substituted alkyl, aryl, arylalkyl, or cycloalkyl. Preferabiy, Y is a 5-or 6- member heteroaryl ring. Furthermore, W may be -(CHOE-S(=O).Y, wherein j is l or 2, b is O, l, 2, or 3, Y as aryl, alkyl, arylalkyl, cycloalkyl, alkynyi, heteroaryl, NKRR, provided that when r is l, £ 1 = CK;, , and wherein R14, R:5, and Rit- are eacn independently hydrogen, or unsubstituted or substituted alkyl, aryl, arylalkyl, or cycloalkyl. In another embodiment, R, is selected f rom the grcup consisting of substituted and unsubstituced phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinal, pyrrolyl, triazoiyl, thioazolyl, oxazolyl, oxadiazolyl, pyrazolyl, furanyl, methylenedioxyphenyl, and thiophenyl. When R3 is phenyl, ic may be substituted with, for example, hydroxyl, alkoxy (e.g., methoxy), alkyl (e.g., tolyl), and halogen, (e.g., c-, m-, or p- fluorophenyl or o-, m-, or p- chlorophenyl) . Advantageously, R, may be 2-, 3-, or 4- pyridyl or 2- or 3-pyrimidyl. The invention also pertains to a deazapurine wherein R6 is hydrogen or Cl-C3 alkyl. Preferably, R6 is hydrogen. The invention also includes deazapurines wherein Rj is hydrogen, and R: is substituted or unsubstituted alkyl or alkoxy, substituted or unsubstituted alkylamine, arylamine, or alkylarylamine, substituted or unsubstituted aminoalkyl, amino aryl, or aminoalkylaryl, substituted or unsubstituted alkylamide, arylamide or alkylarylamide, substituted or unsubstituted alkylsulfonamide, • arylsulfonamide or alkylarylsulfonamide, substituted or unsubstituted alkylurea, arylurea or alkylarylurea, substituted or unsubstituted alkylcarbamate, arylcarbamate or alkylarylcarbamate, or substituted or unsubstituted alkylcarboxylic acid, arylcarboxylic acid or alkylarylcarboxylic acid. Preferably, R: is substituted or unsubstituted cycloalkyl, e.g., mono- or dihydroxy-substituted cyclohexyl or cyclopentyl {preferably, monohydroxy-substituted cyclohexyl or monohydroxy-substituted cyclopentyl) . Advantageousiy, R: may be of che rollowing formula wherein A is Ca-C alkyl, (Figure Removed) C3-C7 cycloalkyl, a chain of one to seven atoms, or a ring of three to seven atoms, opţionaliy substituted with Cx-Cj alkyl, halogens, hydroxyl, carboxyl, thiol, or amino groups; wherein B is mechyl, N(Me);, N(Ec):, NHMe, NHSt, (CH;)rNH3+, NH(CH2)rCH3/ (CH,).NH.( (CH:) rCHCK?NH;, (CH2)rNHMe, (CH:)rOK, CH2CN, (CH:)P.CO:K, CHR1?Ri?1 or CHMeOH. wherein r is an integer f rom O to 2, m is l or 2, R1:- is alkyl, R:9 is NH3+ or CO;H or R16 and R1? together are: (Figure Removed) wherein p is 2 or 3; and Rn is Cj-C alkyl, C3-C-7 cycloalkyl, a chain of one to seven atoms, or a ring of three to seven atoms, optionally substituted with Ca-C6 alkyl, halogens, hydroxyl, carboxyl, thiol, or amino groups. Advantageously, A is unsubstituted or substituted C1-C6 alkyl. B may be unsubstituted or unsubstituted C:-C6 alkyl. In a preferred embodiment, R: is of the formula -A-NHC(-0)B. In a particularly advantageous embodiment, A is -CH:CH2- and B is methyl. The compounds of the invention may comprise water-soluble prodrugs which are metabolized in vivo to an active drug, e.g., by esterase catalyzed hydrolysis. Examples of potenţial prodrugs include deazapurines with, for example, R2 as cycloalkyl substituted with -OC(0)(Z)NH2/ wherein Z is a side chain of a naturally or unnaturally occurring ar.ir.: acid, or analog chereof, ar. a, E, \, or u amino acid, cr c dipeptide. Preferred amino acid side chains include those oi glycine, alanine, valine, leucine, isoleucine, lysine, o-tnethylalanine, aminocyclopropane carboxylic acid, azeridine-2-carboxylic acid, 3-alanine, v-aminobutyric acid, alanine-alanine, or glycine-alanine. In anocher embodiment, R: and R: together are: (Figure Removed) wherein n is l or 2, and wherein the ring may be optionally subscituted with one or more hydroxyl, amino, thiol, carboxyl, halogen, CH2OH, CH,NHC (=0) alkyl, or CH2NHC(-0)NHalkyl groups. Preferably, n is l or 2 and said ring is subscituted with -NHC(=0)alkyl. In one advantageous embodiment, Rj is hydrogen, R; is substituted or unsubstituted C,-Ci alkyl, R3 is substituted or unsubstituted phenyl, R4 is hydrogen, L is hydrogen or substituted or unsubstituted C;-C6 alkyl, Q is O, S or NR7, wherein R-» is hydrogen or substituted or unsubstituted C^-C6 alkyl, and W is substituted or unsubstituted aryl. Preferaiily, R: is -A-NHC(-O)B, wherein A and B are each independently unsubstituted or substituted C^-C, alkyl. For example, A may be CH^CH^. B may be, for example, alkyl (e.g., methyl), or aminoalkyl (e.g., aminomethyl). Preferably, R3 is unsubstituted phenyl and L is hydrogen. R6 may be methyl or preferably, hydrogen. Preferably, Q is O, S, or NR7 wherein R7 is hydrogen or substituted or unsubstituted Ca- C6 alkyl, e.g., methyl. W is unsubstituted or substituted phenyl (e.g., alkoxy, halogen substituted). Preferably, W is p-fluorcphenyl, p-chlorophenyl, or p-mechoxyphenyl. W -a y also be heteroaryl, e.g-., 2-pyridyl. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoechyl) amino-6-phenoxymethyl-2-phenyl-7«- pyrrolo [2,3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6-(4-fluorophenoxy)methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. In a particularly preferred etnbodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6-(4-chlorophenoxy)methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6-(4-methoxyphenoxy)methyl-2-phenyl-7/f-pyrrolo [2, 3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6-(2-pyridyloxy)methyl-2-phenyl-7#-pyrrolo[2,3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6-(N-phenylamino)methyl-2-phenyl-7#-pyrrolo[2,3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-acetylaminoethyl) amino-6- (N-methyl-N-phenylamino) methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. In a particularly preferred embodiment, the deazapurine is 4-(2-N'-methylureaethyl) amino-6-phenoxymethyl-2-phenyl- 7H- pyrrolo[2,3d]pyrimidine. The invention further pertains to a method for inhibiting the y oi a.n aaenosine receptor (e.g., an A;. • receptor) in a cell by contacting the cell wich a compound c: the invention. Preferably, the compound is ar. antagonist c£ che receptor. The invention also pertains to a method for creaiing a gascrointestinal disorder (e.g., diarrhea) in ar. ar.imal by administering to an animal an effective amount of a compound of the invention (e.g., an antagonist ot A;t) . Preferably, che animal is a human. In another embodiment, the invention relates to a pharmaceutical composition containing an N-6 substituted 7-deazapurine of the invention and a pharmaceutically acceptable carrier. The invention also pertains to a method for treating a N-6 substituted 7-deazapurine responsive state in an animal, by administering to a mammal a therapeutically effective amount of a deazapurine of the invention, such that treatment of a N-6 substituted 7-deazapurine responsive state in the animal occurs. Advantageously, the disease state may be a disorder mediated by adenosine. Examples of preferred disease states include: central nervous system disorders, cardiovascular disorders, renal disorders, inflammatory disorders, allergic disorders, gastrointestinal disorders, eye disorders, and respiratory disorders. The term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. The term alkyl further includes alkyl groups, which can further include oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more carbons of the hydrocarbon backbone, e.g., oxygen, nitrogen, sulfur or phosphorous atoms. In preferred embodiments, a straight chain or branched chain alicyl has 30 or fewer carbor. acoms ir. its backbone (e.g -°r straighc chain, -j"-3: ---" branched chain), and mare preferably 20 or fewer. Likewise, preferred cycloalkyls have f rom 4-10 carbon atoms ir. cheir ring structure, and more preferably have 5, 6 or 7 carbor.s ir. the ring structure. Moreover, the terni alkyl as used throughout che specificacion and claims is intended to include both "unsubstituted alkyis" and "substituted alkyis", the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxvcarbonyloxy. aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), araidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. Cycloalkyls can be further substituted, e.g., with the substituents described above. An "alkylaryl" moiety is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)). The term "alkyl" also includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyis described above, but that contain at least one double or triple bond respectively. " The term "aryl" as used herein, refers to the radical of aryl groups, including 5- and 6-membered single-ring aromatic groups that may include f rom zero to four heteroatoms, for example, benzene, pyrroie, fur ar., thiophene, ir.idazcle, benzoxazole, benzothiazole, triazole, tetrazoie, pyrazc-le, pyridine, pyrazine, pyridazine and pyrimidine, ar.d the like. Aryl groups also include polycyclic fused aromatic groups such as naphchyl, guinolyl, indolyl, and the like. Those aryl groups having heteroatoms in the ring structura may also be referred to as "aryl hererocycles", "heteroaryis" or "heteroaromatics". The aromatic ring can be substitute:: at one or more ring positions with such substituents as described above, as for example, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroarornatic moiecy Aryl groups can also be fused or bridged with alicyclic or heterocyclic rings which are not aromatic so as to form a polycycle (e.g., tetralin). The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively. For example, the invention contemplates cyano and propargyl groups. Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having f rom one t o' ten carbons, more preferably f rom one to six carbon atoms in its backbone structura, even more preferably one to three carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. The terms "alkoxyal)cyl", "polyatninoaikyl" ar.d "thioalkoxyalkyl" refer to alkyl groups, as described above. which further include oxygen, nitrogen cr sulfur atons replacing. one or more carbons of che hydrocarbor. backbone, e.g., oxygen, nitrogen or sulfur atoms. The terms "polycyclyl" or "poiycyclic radical" refer te the radical of two or more cyclic rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) ir. which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are jcined through non-adjacent atoms are termed "bridged" rings. Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbarnoyl and ureido) , amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkyl, alkylaryl, or an aromatic or heteroaromatic moiety The term "heteroatom" as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur and phosphorus. The term "amino acids" includes naturally and unnaturally occurring amino acids found in proteins such as glycine, alanine, valine, cysteine, leucine, isoleucine, serine, threonine, methionine, glutamic acid, aspartic acid, glutamine, asparagine, lysine, arginine, proline, histidine, phenylalanine, tyrosine, and tryptophan. Amino acid analogs include amino acids with lengthened or shortened s ide chair.s or varian" side chains wich appropriate funcţional groups. Amino acids also include D and L scereoisomers of ar. ar.inc acid when the structure of the amino acid admics of stereoisomeric forms. The cerm "dipeptide" includes two or more amino acids linked together. Preferahly, dipepcides are cwo amino acids linked via a peptide linkage. Parcicularly preferred dipeptides include, for example, alar.ine-alanine and glycine-alanine. It will be noted that the structure of some of the compounds of this invention includes asymmetric carbon atoms and thus occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. All such isotneric forms of these compounds are expressly included in this invention. Each stereogenic carbon may be of the R or S configuration. It is to be understood accordingly that the isomers arising f rom such asymmetry (e. g., all enantiomers and diastereomers) are included within the scope of this invention, unless indicated otherwise. Such isomers can be obtained in substantially pure form by classical separation techniques and by stereochemically controlled synthesis. The invention further pertains to pharmaceutical compositions for treating a N-6 substituted 7-deazapurine responsive state in a mamtnal, e. g., respiratory disorders (e. g., asthma, bronchitis, chronic obstructive pulmonary disorder, and allergic rhinitis), renal disorders, gastrointestinal disorders, and eye disorders. The pharmaceutical composition includes a therapeutically effective amount of a N-6 substituted 7-deazapurine, described supra, and a pharmaceutically accepcable carrier.i It is to be understood, that all of the deazapurines described above are included for therapeutic treatment. It is to be further understood that the deazapurines of the invention can be used alone or in combination with other deazapurines of the invention or in combination with additional therapeutic compounds, suc.-, as antibiotics, antiinflammatories, or anticancer ager.rs, fer example. The term "antibiotic" is art recognized and is intended to include those substances produced by growing microcrgar.isms and synthetic dcrivatives thereof, which eliminate or inhibit growth of pathogens and are selectively toxic to the pathogen while producing minimal or no deleterious effects upon the infected host subject. Suitable examples of antibiotics include, but are not limited to, the principie classes of aminoglycosides, cephalosporins, chloramphenicols, fuscidic acids, macrolides, penicillins, polymixins, tetracyclines and streptomycins. The term "antiinflammatory" is art recognized and is intended to include those agents which act on body mechanisms, without directly antagonizing the causative agent of the inflammation such as glucocorticoids, aspirin, ibuprofen, NSAIDS, etc. The term "anticancer agent" is art recognized and is intended to include those agents which diminish, eradicate, or prevent growth of cancer cells without, preferably, adversely affecting other physiological functions. Representative examples include cisplatin and cyclophosphamide. When the compounds of the present invention are administered as pharmaceuticals, to humans and mammals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination wich a pharmaceutically acceptable carrier. The phrase "pharmaceuticallyl acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liguid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound(s) of the cresent invention withir. or to the suc^ecr sucf. tnat ir c s r. oerforrns its intended function. Typically, such compound? are carried or transportec f rom one crgar.. or port ier. of the faody, to another organ, or portion of che body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulat ion and noc ir.jurious t o che patient. Some examples of materials which car. serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin,- talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oii, cottonseed oii, safflower oii, sesame oii, olive oii, corn oii and soybean oii; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As set out above, certain embodiments of the present compounds can contain a basic funcţional group, such as amino or alkylamino, and are, thus, capable of forming pharmaceutically acceptable salts with pharmaceutically acceptable acids. The term "pharmaceutically acceptable salts" in this respect, refers to the relatively non-toxic, inorganic and organic acid addition salts of compounds of the present invention. These salts can be prepared in si tu during the final isolation and purification of the compounds of the invention, or by separately reacting a purified compound of the invention in its free base foim with a suitable organic or inorganic acid, and isolating the salt thus formed. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acerate, valerate, eleate, paimitate, stearaze, _aurat=. benzoate, lactate, phosphate, tosylate, citrate, -aieats, fumarate, succinate, tartrate, napthyiate, mesylâ-a, glucoheptonare, lactobionate, and laurylsulphonate salts ar.d che like. (See, e.g., Berge ec al. (1977) "Pharnaceutical Salts", J. Pharat. Sci. 66:1-19). In other cases, the compounds of che present invention may concain one or more acidic funcţional groups and, thus, are capable of forming phannaceutically acceptable salts with pharmaceutically acceptable bases. The term "phannaceutically acceptable salts" in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in situ during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. The term "pharmaceutically acceptable esters" refers to the relatively non-toxic, esterified products of the compounds of the present invention. These esters can be prepared in si tu during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent. Carboxylic acids can be converted into esters via treattnent with an alcohol in the presence of a catalyst. Hydroxyl containing derivatives can be converted into esters via crearmenr with ar. estenfy.ng agent such as alkanoyl halides. The term is further intended te include lower hycrocarrcr. groups capable of being solvated under physiologiral conditions, e.g., alkyl esters, methyl, ethyl and propyl esters. (See, for example, Berge et al., supra.) The invention further contemplates the use of prodrugs which are converted in vivo to the therapeutic compcunds of the invention (see, e.g., R.B. Silverman, 1992, "The Organic Chemistry of Drug Design and Drug Action", Academic Press, Chapter 8}. Such prodrugs can be used to alter the biodistribution [e.g., to allow compounds which would not typically enter the reactive site of the protease) or the pharmacokinetics of the therapeutic compound. For example, a carboxylic acid group, can be esterified, e.g., with a methyl group or an ethyl group to yield an ester. When the ester is administered to a subject, the ester is cleaved, enzymatically or non-enzymatically, reductively or hydrolytically, to reveal the anionic group. An anionic group can be esterified with moieties (e.g., acyloxytnethyl esters) which are cleaved to reveal an intermediate compound which subsequently decomposes to yield the active compound. In another embodiment, the prodrug is a reduced form of a sulfate or sulfonate, e.g., a thiol, which is oxidized in vivo to the therapeutic compound. Furthermore, an anionic moiety can be esterified to a group which is actively transported in vivo, or which is selectively taken up by target organs. The ester can be selected to allow specific targeting of the therapeutic moieties to particular reactive sites, as described below for carrier moieties. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions. Sxamples of pharmaceutically acceptable antioxidants include: water soiuble anrioxidants, such as asccrbic acid, cysteir.e hydrochloride, sodium bisulfate, sodium mecabisuifiţe, scdiur. sulfiţe and the like; oil-solubie ancioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (SKAÎ , butylated hydroxycoluene (BKT), lecithin, propyl gallate, aipha-tocopherol, and the like; and metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid !EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Formulations of the presant invention include those suitable for oral, nasal, topical, transdermal, buccal, sublingual, rectal, vaginal and/or parenteral administrat ion. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage ferm will generally be that amount of the compound which produces a therapeutic effect. Generally, out of one hundred per cent, this amount will range f rom about l per cent to about ninety-nine percent of active ingredient, preferably from about 5 per cent to about 70 per cent, most preferably from about 10 per cent to about 30 per cent. Methods of preparing these formulations or compositions include the step of bringing into association a compound o£ the present invention with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an agueous or non-aqueous liguid, cr as an oii-ir.-water cr water-in-c;._ _i::uic emulsion, cr as ar. elixir or syrup, or as pastilles lusir.g ar. inert faase, such as gelatin and glycerir., cr surrose ar.d acacia) and/cr as mouth washes and the iike, each ccr.tâir.ing a predecermined amount of a compound of che presant ir.ver.ticr. as an active ingredient. A compound of the preser.t invention may also be administered as a bolus, electuary or paste. In solid dosage forms of the inventicr. for oral administration (capsules, tablets, pills, dragees, powders, granules and the Iike), the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certam silicates, and sodium carbonate; solution retarding agents, such as paraffin; absorption accelerators, such as guaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol and glycerol monostearate; absorber.ts, such as kaolin and bentonite clay; lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pha'rmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may alsc be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the Iike. A tabiet may be made by compression or molding, optionally wich one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, oreservative, disintegrant (for example, sodiu:?, s» ar c h glycolate or cross-linked sodium carboxymethyl celiulose), surface-accive or dispersing agent. Molded tabiets may be made by molding in a suicable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets, and other solid dosage forms of the pharmaceutical compositions of the present inventior., such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical- formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl celiulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be sterilized by, for example, filtration through a bacteria- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in' sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. Liguid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert dilutents commonly used in the arc, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcchol, benzyl benzoate, propylene glycol, l, 3-bucyler.s glycol, oils (in particular, coctonseed, groundnu::, cern, gerrr, olive, castor and sesame oils), glycerci, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert dilutents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. Formulations of the pharmaceutical compositions of the invention. for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound. Formulations of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate. Dosage forms for the topical or transdermal administration of a compound of this 'invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be reguirec. The ointments, pastes, creams and gels may contam, ir. addition 'to an active compound of chis invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, benconites, silicic acid, talc ar.c zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the active compound in a polymer matrix or gel. Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention. Preferably, the pharmaceutical preparation is an ophthalmic formulation (e.g., an periocular, retrobulbar or intraocular injection formulation, a systemic formulation, or a surgical irrigating solution). The ophthalmic formulations of the present invention may include one or more deazapurines and a pharmaceutically acceptable vehicle. Various types of vehicles may be used. The vehicles will generally be aqueous in nature. Aqueous solutions are generally preferred, based on case of reguirec. The ointments, pastes, creams and gels may contam, ir. addition 'to an active compound of this invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, pelyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the active compound in a polymer matrix or gel. Ophthalmic fortnulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention. Preferably, the pharmaceutical preparation is an ophthalmic formulation (e.g., an periocular, retrobulbar or intraocular injection formulation, a systemic formulation, or a surgical irrigating solution). The ophthalmic formulations of the present invention may include one or more deazapurines and a pharmaceutically acceptable vehicle. Various types of vehicles may be used. The vehicles will generally be aqueous in nature. Aqueous solutions are generally preferred, based on case of formulation, as well as a pacient's abiiity te easily administer such compositions by means of instillir.g one tr two drops of the solutions in the affected eyes. However, the deazapurines of the present invention may aiso be readily ! incorporated into other types of compositions, such as suspensions, viscous or semi-viscous gels or other types of solid or semi-solid compositions. The ophthalnic compositions of the present invention may also include various other ingredients, such as buffers, preservatives, co-solvents and viscosity building agents. An appropriate buffer system (e.g., sodium phosphate, sodium acetate or sodium borate) may be added to prevent pH drift under storage conditions. Ophthalmic products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: benzalkoniutn chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, polyquaternium-l, or other agents known to those skilled in the art. Such preservatives are typically employed at a level of f rom 0.001 to l. OV weight/volume ("% w/v") . When the deazapurines of the present invention are administered during intraocular surgical procedures, such as through retrobulbar or periocular injection and intraocular perfusion or injection, the use of balanced salt irrigating solutions as vehicles are most preferred. BSS® Sterile Irrigating Solution and BSS Plus® Sterile Intraocular Irrigating Solution (Alcon Laboratories, Inc., Fort Worth, Texas, USA) are examples of physiologically balanced intraocular irrigating solutions. The lâtter type of solution îs described in U.S. Pat. No. 4,550,022 (Garabedian, et ai.), the entire contents of which are hereby incorporated in the present specification by reference. Retrobulbar and periocular injections are known to those skilled in the art and are described ir. numerous publications inciuding, fcr exaraple, Ophchalmic Surgery: Principies of Practice, Ed., G. L. Spaech. W. B. Sanders Co., Philadelphia, Pa., U.S. A., pages 85-87 (1990). As indicated above, use of deazapurines co prever.r cr reduce damage ta retinal and optic nerve head tissues ar the cellular level is a particularly important aspect of one embodiment of the invention. Ophthalmic conditions which may be treated include, but are not limited to, retinopathies, macular degeneration, ocular ischemia, glaucoma, and damage associated with injuries to ophthalmic tissues, such as ischemia reperfusion injuries, photochemical injuries, and injuries associated with ocular surgery, particularly injuries to the retina or optic nerve head by exposure to light or surgical instruments. The compounds may also be used as an adjunct to ophthalmic surgery, such as by vitreal or subconjuneţival injection following ophthalmic surgery. The compounds may be used for acute treatment of temporary conditions, or may be administered chronically, especially in the case of degenerative disease. The compounds may also be used prophylactically, especially prior to ocular surgery or noninvasive ophthalmic procedures, or other types of surgery. Pharmaceutical compositions of this invencion suitable for parenteral administration comprise one or more compounds of the invention in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulat ion isotonic with the blood of the intended recipient or suspending or thickening agents. • Examples of suitable aqueous and nonaqueous carriers which may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol. propylene glyccl, polyethylene glycoi, and the lika! , ar.d suitable mixtures thereof, vegetable oils, such as olive oii. and injectable organic esters, such as ethyl oleate. Prcper fluidicy can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required partide size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservativcs, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may bc ensured by the inciusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inciusion of agents which delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oii vehicle. Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polytner employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable Eormulations are also prepared by enrrapcing the drug ir. Liposoraes or microemulsior.s which are corapatibie with body lissue. The preparations of the present invencion may be giver. orally, parenterally, topically, or rectally. They are of course given by forms suitable for each administraiion route. For example, they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administration is preferred. The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous,. subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. The phrases "systemic administration," "administered systematically," "peripheral administration" and "administered peripherally" as used herein mean the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration. These compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. Regardless of the route of administrat ion selectec, the compounds of the presant invention, which may be used ir. a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formuiated intc pharmaceutically acceptable dosage forms by convenţional methods known to those of skill in the art. Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be variec so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being employed. the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required For example, the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is dchieved. In general, a suitable daily dose of a compound of the invention will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect. Such an effeccive dose will generally depend upon the faczsrs described above. Generally, intravenous and subcutaneous doses of the compounds of chis invention for a patient, wher. used for the indicated analgesic effects, will range frorr. about 0.0001 to about 200 mg per kilogram of body weight per day, more preferably f rom about 0.01 t o about 150 mg per kg per day, and still more preferably f rom about 0.2 to about 140 mg per kg per day. If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. while it is possible for a compound of the present invention to be administered alone, it is preferable to administer the compound as a pharmaceutical composition. The present invention also pertains to packaged pharmaceutical compositions for treating a N-6 substituted 7 deazapurine responsive state, e.g., undesirable increased adenosine receptor activity in a mammal. The packaged pharmaceutical compositions include a container holding a therapeutically effective amount of at least one deazapurine as described supra and instructions for using the deazapurine for treating the deazapurine responsive state in the mammal. The deazapurines of the invention can be prepared using standard methods for organic synthesis. Deazapurines can be purified by reverse phase HPLC, -chromatography, recrystallization, etc. and their structures confirmed by mass spectral analysis, elemental analysis, IR and/or NMR spectroscopy. Typically, synthesis of the intermediates as well as the deazapurines of the invention is performed in solution. The addition and removal of one or more protecting group is also typical praccice and is icnown co chose skilled ir. Typical synchecic schernes for che preparacion of dea incermediaces of che ir.vencisn are ouclined below i r. I. This invencion furcher provides a compour.d havinc che scruccure (IV): (Figure Removed) wherein R: is crans-4-hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, acecylamino ethyl, or tnechylamino carbonylamino ethyl; wherein Ar is a substituced or unsubscicuted four to six naphchalene, cecralin, benzochiophene, indole, membered ring, phenyl, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1,2,4-criazole, pyridine, 2 (1H)-pyridone, 4 (1H)-pyridone, pyrazine, pyrimidine, pyridazine, isochiazole, isoxazole, oxazole, cetrazole, naphchyridine, benzofuran, 2,3-dihydroindole, IH-indole, indoline, benzopyrazole, l,3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, cecrahydroquinoline, isoguinoline, . benzimidazole, quinazoline, pyrido[2,3-b]pyrazine, pyrido[3,4- bjpyrazine, pyrido[3,2-c]pyridazine, purido [3,4-bJ- pyridine, IH-pyrazole[3,4-d]pyrimidine, pceridine, 2 (1H)-quinolone, l (2H)-isoquinolone, l,4-benzisoxazine, benzochiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, q\iinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phchalazine, cinnoline, or having a scruccure: (Figure Removed) wherein Y is carbon or nitrogen; whereir. Rj. and Rj.' are independently H, substituted or unsubstituted alkyl, substituted or unsubstitutsd aryl, halogen, methcxy. methyl amino, or methyl thio; wherein 4b- is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R-) (ROXfeî wherein X is O, S, or Nî%«-',0 wherein R? and R? are each independently H or alkyl, wherein fe- and rt •R-°are each independently alkyl or cycloalkyl, or NRsRt is a substituted or unsubstituted ring of between 4 and 7 members; wherein R- is H, alkyl, substituted alkyl, cycloalkyl; or a pharmaceutically acceptable salt, a prodrug derivative, or a biologically active metabolite, with proviso that when R: acetylamino ethyl, ~Af- is not 4- pyridyl. -3 In one embodiment of the compound having structure IV, NRaRt is a substituted or unsubstituted ring of between 4 and 7 members which is selected from the group consisting of: (Figure Removed) wherein m is -e-, -0, or 2, (Figure Removed) wherein n is O, l, 2, or 3; wherein Ri is hydrogen, -OH, -CHsOH, -C(=0)NR9Rio, NHRn; wherein Rn is -C(»0)CHa, or - SOsMe, or (Figure Removed) wherein R is H, alkyl, or aryl. In another embodiment of the compound having structure IV, nas the structure: (Figure Removed) wherein Y is carbon or nirogen; wherein R: is H, or halogen, -0-alkyl group, amine group, or sulfide group; wherein -R* is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(RO (RsJNRsRr, wherein R- and Ri are each independently H or alkyl, wherein filând **"are each independently alkyl or cycloalkyl, or R»> A*'0 and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members. In another embodiment of the compound, Y is carbon. In another embodiment of the compound, Re is hydrogen. In another embodiment of the compound, -R*- is hydrogen. In another embodiment of the compound, -Rs- is hydrogen. In another embodiment of the compound, ft» and -R*- are each methyl. In another embodiment of the compound, -IU is -C(R-) (Ri)NRaRt, wherein R- and R? are each independently H or alkyl, wherein and R are each independentiy alkyl or cycloalkyl, cr -s-,'-and the nitrogen together ferm a substituţed or unsubst.tuted ring of between 4 and 7 members. In anorher etnbodiment of che compound, R_- is haicgen. In another embodiment of the compound, Y is nitrogen. In yet another embodiment of the compound, Ri is hycrogen . In a further embodiment of the compound, R* and R hydrogen . This invention also provides a compound having the structure (V) : (Figure Removed) wherein -Rr is aryl, substituţed aryl, or heteroaryl; wherein -fe-is H, alkyl, substituţed alkyl, or cycloalkyl; wherein 9~ is H, alkyl, substituţed alkyl, aryl, arylalkyl, amino, substituţed aryl, wherein ,,said substituţed alkyl is -C(ftr) () NRfc',° wherein R and R are f\. each H or alkyl, wherein -R and -ftare each alkyl or cycloalkyl, or R -Rr and the nitrogen together form a i ring system of between 4 and 7 members. In cns embodirnenc of che compound having scruccure V, -s- ar.d R8 are each H; wherein R4 is K and -R10 is -R10 :C(=O Ri:. In anccher embodimenc of che compound hav^ng scruccure v, and -R8 are each H; wherein che ring syscem is mcrpholino, chiomorphoiino, N-4-subscicuced piperazino, 2-subscicuced piperazine, or R4subscicuced pyrrolidino, piperadine, wherein Ri is K, OH, CKjOK, -C(*O)NR9Rio, NRii, wherein Ri: îs -C(«0)CK3, -S02.MC. In another embodirnent of rhe compound, che compound nas che following scruccure: (Figure Removed) In anocher embodimenc of che compound, Che compound has the scruccure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) (Compound 1318-b) In another embodiment of the compound, the compound has tr.s structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In ancther etnbodiraent of the compound, the compou structure: (Figure Removed) compound having the structure (Figure Removed) wherein -B, is a 5-6 membered aromatic ring; wherein-R,- and-Rrare independently H, or alkyl. In one embodiment of the compound, the compound nas z'ns structure: (Figure Removed) In one embodiment of the compound, the compound nas the structure: (Figure Removed) In another embodiment of the compound, the compound hai structure: (Figure Removed) In another embodiment of compound 1500, the compound has the structure: (Figure Removed) In a further embodiment of the compound, the compound has the structure: (Figure Removed) This invcnticn aiso provides a compound having the strurrure (Figure Removed) wherein -R-. is a 5-B membered aromatic ring; wherein -Rr **^(â and T are indepcndently H, or alkyl; with the proviso that is not 4-pyridyl. In one embodiment of the compound, the compound nas the structure: (Figure Removed) This inv-r.iion furrher provides a corroounc h a v structure: (Figure Removed) wherein-ftr- is a substituted 5-6 tnembered aromatic ring; wherein-% and-Rr are independently H, or alkvl. In one emboditnent of the compound, the compound has the structure: (Figure Removed)This invention also provides a compound having the szructurs (Figure Removed) - wherein R- is a 5-6 membercd aromatic ring; whercin X is oxygen, or sulfur. In one embodiment of the compound, the compound nas the structura: (Figure Removed) This invention aiso provides a compound having ti e scru — ure (Figure Removed) wherein Je- is a 5-6 membcred aromatic ring; wherein X is oxygen, or sulfur. In one etnbodiment of the compound, the compound has the structure: This invention further provides a method for rresrir.c a disease associated with A: adenosine receptor in £ subiect, comprising adninistering to the subject a therapeuticaiiy effective amount of a compound having the formula IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, che subject is a rr.ammal. In another embodiment of the method, the mammal is a human. In another embodiment of the method, the Ai adenosine receptor is associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, cr ulcerative condition. This invention also provides a combination therapy for asthma, comprising compounds IV and V, and a steroid, p2 agonist, glucocoticoid, lucotriene antagonist, or anticolinegic agonist. Diseases associated with adenosine Ai, A2a, A2b and A3 receptors are disclosed in WO 99/06053 and WO-09822465, WO-09705138, WO-09511681, WO-09733879, JP-09291089, PCT/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-soluble prodrug of a compound having the structures IV, V, VI, VII, VIII, IX, or X, wherein said water-soluble prodrug that is metabolized in vivo to an active drug which selectively inhibit Ai adenosine receptor. In one embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pharmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier. (Figure Removed) This ir.vention further prcviaes a method for inhibitine the activity of an Ai adenosine recepcor in a ceil. which comprises contacting said cell with a compound havino the structures IV, V, VI. VII, VIII, IX, or X. In one embodiment of the method, the compound is an antagonist of said Ai adenosine receptor. This ir.vention also provides for a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, the subject is a human. In another method of the method, the compound is an antagonist of Ai adenosine receptors. This invention also provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method, said compound is an antagonist of Ai adenosine receptors. This invention further provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX. or X. In one embodiment of the method, said damage cor.prises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic. In another embodiment of the method, wherein said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of Ai adenosine receptors. This invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X, and a pharmaceutically acceptable carrier. In another embodiment of the pharmaceutical composition, said therapeutically effective amount is effective to treat a respiratory disorder or a gastrointestinal disorder. In another embodiment of the pharmaceutical composition, said gastrointestinal disorder is diarrhea. In another embodiment of the pharmaceutical composition, said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pnarmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In yec another embodiment of the pharmaceutical composition. said pharmaceutical composition is a systemic f ortr.ulaticr.. In a further embodimer.c of the pharmaceuzical preparatior., said pharmaceutical composition is a surgical irrigacing solution. This invcntion also provides a packaged pharrcaceurical composition for treating a disease associated with Ai adenosine receptor in a subject, comprising.- (a) a container holding a therapeutically effective amount of an adenosine Al specific compound; and (b) instructions for using said compound for treating said disease in a subject. As used herein, "A compound is Ax selective." means that a compound nas a binding constant to adenosine Al receptor of at least ten titne higher then that to adenosine A;a, A:b or A3. This invention also provides a method of preparing the compound having structure IV, comprising the steps of (Figure Removed) c) treating the product of step b) under suitable conditions io provide (Figure Removed) d) treating the chiorinated product of step c) with NH2R.I to provide (Figure Removed) wherein R1 is trans-4-hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, acetylamino ethyl, or methylamino carbonylamino ethyl; wherein R3 is a substituted or unsubstituted four to six membered ring; wherein RS is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R-) (R6) XR9, wherein X is O, S, or NR10, wherein R7 and Rg are each independently H or alkyl, wherein Rg and RIQ are each independently alkyl or cycloalkyl, or NRgRio is a substituted or unsubstituted ring of between 4 and 7 members; wherein R6 is H, alkyl, substituted alkyl, cycloalkyl; or a pharmaceutically acceptable salt, or a prodrug derivative, or a biologically active metabolite; with the proviso that when RI is acetylamino ethyl, R3 is not 4-pyridyl. This invention also provides a method of preparing the compound having structure comprising the steps of (Figure Removed) wherein P is a removable protecting group; b) treating the product of step a) under cyclization conditions to provide (Figure Removed) c) treating the product of step b) under suitable condilions to provide (Figure Removed) d) treating the chiorinated product of step c) with provide (Figure Removed) e) wherein fe-is aryl, substizuted aryl, heteroaryl; & wherein -fe-îs H, alkyl, substituted alkyl, or cycioaikyl; wherein -fts- is H, alkyl, subscituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said subsrituted alkyl is -CHW (-ft-ONRfc, wherein-£r-and -R are each E or alkyl, wherein -R- and –R are each alkvl cr ' cycloalkyl, or N3tRî is a ring system of between 4 and ~ members. Compounds represented by formula VI, VII, and viu can be synthesized by any of the Schemes I-VIII. Compounds represented by formula IX, and X can be prepared by Scheme IX. The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. This invention will be better understood from the Experimental Details which follow. However, one skilled in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. The deazapurines of the invention can be prepared usir.c standard methods for organic synthesis. Deazapurines car. be purified by reverse phase KPLC, chromatography, recrystallization, etc. and their structures confirmed by mass spectral analysis, elemental analysis, IR and/or NMR spectroscopy. Typically, synthesis of the intermediates as well as the deazapurines of the invention is performed in solution. The addition and reraoval of one or raore protecting group îs also typical practice and is known to those skilied in the art. Typical synthetic schemes for the preparation of deazapurine intermediates of the invention are outlined below in Scheme I. (Figure Removed) wherein R3, R and Rg are as defined above. In general, a protected 2-amino-3-cyano-pyrrole can be treated with an acyl halide to form a carboxyamido-3-cyano-i pyrrole which can be treated with acidic methanol to effect ring closure to a pyrrolo[2,3d]pyrimidine-4 (3H) -one (Muller, C.S. et al. J. Med. Chem. 40:4396 (1997)). Removal of the pyrrolo protecting group followed by treatment with a chlorinating reagent, e.g., phosphorous oxychloride, produced substituted or unsubstituted 4-chloro-7H- pyrrolo[2,3d]pyrimidines. Treatment of the chloropyrimidine with amines afforded 7-deazapurines. For example, as shown in Scheme I, a N- (1-dl-phenylethyl) -2- amino-3-cyano-pyrrole was treated with an acyl halide in pyridine and dichloromethane. The resultant N-d-dl- phenylethyl)-2-phenylcarboxyamido-3-cyano-pyrrole was treated with a 10:1 mixture of methanol/sulfuric acid to effect ring closure, resulting in a dl-7H-7-(l- phenylethyl (pyrrolo [2, 3d] pyrimidine-4 (3H)-one. Removal of the phenylethyl group by treatment of the pyrimidine with polyphosphoric acid (PPA) followed by POC13 afforded a key intermediate, the 4-chloro-7H-pyrrolo[2,3d]pyrimidine. Further treatment of the 4-chloro-7H-pyrrolo[2,3d]pyrimidine with various arnines listed in Table l gives compounds of formula (Figure Removed) A general approach to prepare 6-substituted pyrroles is depicced in the following scheme (Scheme II). Scheme II (Figure Removed) wherein R1 through R$ are as defined above. Transcsterification and alkylation of ethyl cyanoacetate with an a-haloketone affords a ktotnethylester. Protection of the ketone followed by treatment with an amidine (e.g., alkyl, aryl or alkylaryl) hydrochloride produced the resultant ketal protected pyrimidine. Removal of the protecting group, followed by cyclization and treatment with phosphorous oxychloride afforded the chloride intermediate which could be further treated with an amine to afford an amine 6- substituted pyrrole. Additionally, alkylation of the pyrrcls nitrogen can be achieved under arc recognized conditions. A general approach to prepare 5-substituted pyrroles is depicted in the following scheme (Scheme III). (Figure Removed) wherein Rj through R6 are defined as above and R is a removable protecting group. Condensation of malononitrile and an excess of a ketone followed by bromination of the product afforded a mixture of starting material, monobrominated and dibrominated products which were treated with an alkylamine, arylamine or alkylarylamine. The resultant amine product was acylated with an acid chloride and the monacylated pyrrole wascyclized in the presence of acid to afford the correspondir.c pyrimidine. The pyrrole protccting group was removed wich polyphosphoric acid and treated with phosphorous oxychicride to produce a chlorinated product. The chlorinated pyrrole could subseguently be treated with an amine to produce an amino 5-substituted pyrrole. AlJcylation of the pyrrole nitrogen can be achieved under art recognized concitions. Schemes IV and V depict methods for preparing the deazapurines l and 2 of the invention. (Figure Removed) wherein R5 and Rg are as described above, e. gr., Secific Prear a t ion of 6-metl The key reaction toward 6-methylpyrrolopyrimidines (1) 013] was cyclization of a cyanoacetate with benzamidine to a pyrimidine. It was believed methyl cyanoacetate would cyclize more efficiently with benzamidine to a pyrimidine than the corresponding ethyl ester. Therefore, transesterification and alkylation of ethyl cyanoacetate in the presence of NaOMe and an excess of an a-haloacetyl moiety, e. g., chloroacetone, gave the desired methyl ester (3) in 79% yield (Scheme IV) . The ketoester (3) was protected as the acetal (4) in 81% yield. A new cyclization method to the pyrimidine (5) was achieved with an amidine hydrochloride, e. g., benzamidine hydrochloride, with 2 equivalents of DBU to afford the 5 in 54% isoiaied yieid. This method improves the yield from 20% using the publishec conditions, which utilizes NaOMe during the cyciization with guanidine. Cyclization to the pyrrole-pyrimidine (6) was achieved via deprotection of the acetal in aqueous HCl in 78% yield. Reaction of (6) with phosphorous oxychloride ac reflux gave the corresponding 4-chloro derivative (7) . Coupling with trans-4-aminocyclohexanol in dimethyl sulfoxide at 135°C gave (1) in 57% from (7) . One skilled in the art will appreciate that choice of reagents allows for great flexibility in choosing-the desired substituent R$. Scheme IV (Figure Removed) Cpgeifle Prgparation of 5-snethylpyT'T'plopyT'in^dlBeB Knoevengel condensation of malononicrile and an excess ketone, e.g., acetone in refluxing benzene gave 8 in 50% yield after distillation. Bromination of 8 with N- bromosuccinimde in the presence of benzoyl peroxide in chloroform yielded a mixcure of starting material, mono- (9), and di-brominated products (5/90/5) after distillation (70%). The mixture was reacted with an a-methylalkylamine or a-methylarylamine, e.g., a-methylbenzylamine, to deliver the aminopyrrole (10) . After passing through a short silica gel column, the partially purified amine (31% yield) was acylated with an acid chloride, e.g., benzoyl chloride to deliver mono- (11), and diacylated (12) pyrroles, which were separated by flash chromatography. Acid hydrolysis of the disubstituted pyrrole (12) generated a combined yield of 29% for the acylpyrrole (11) . Cyclization in the presence of concentrated sulphuric acid and DMF yielded (13) (23%), which was deprotected with polyphosphoric acid to (14). Reaction of (14) with phosphorous oxychloride at reflux gave the corresponding 4-chloro derivative (15). Coupling with crans- 4-aminocyclohexanol in dimethyl sulfoxide at 135°C gave (2) [R6 - CH3] in 30% f rom (14) (See Scheme V) . One skilled in the art will appreciate that choice of reagents allows for great flexibility in choosing the desired substituent R Scheme V (Figure Removed) Ş-aethyl pyrrolopyriaidinag : This alternative route to Rg-substituted pyrroles, e. g., 5- methylpyrrolopyrimidines, involves transesterification and alkylacion of ethyl cyanoacetate to (16) (Scheme VI) . The condensation of (16) with benzamidine hydrochloride with 2 eguivalents of DBU affords the pyrimidine (17) . Cyclization to the pyrrol e -pyrimidine (14) will be achieved via deprotection of the acetal in aqueous HC1. Reaction of (14) with phosphorous oxychloride at reflux gave the corresponding 4-chloro derivative (15) . Coupling with trans-4- aminocyclohexanol in dimethyl sulf oxide at 135°C gives 2. This procedure reduces the number of synthetic reactions to the target compound (2) f rom 9 to 4 steps. Moreover, the yield is dramatically improved. Again, one skilled in the art will appreciate that choice of reagents allows for great f lexibilicy in choosing the desired substituent R6 . Scheme VI (Figure Removed) A general approach to prepare des-methyl pyrrole is depicted in the following scheme (Scheme VII) (Figure Removed) Commercially available methyl cyanoacetate was alJcylated with bromoacetaldehyde diethyl acetal iri the presence of potassium carbonate and Nai to yield (19) . Cyclization to the pyrimidine (20) was achieved in two steps. Initially, the pyrinudine-acetal was forrned via reaction of (19) with benzamidine hydrochloride with 2 equivalents of DBU. The resultant pyrimidine-acetal was deprotected without purification with aqueous l N HCl and the resultant aidehyds cyclizcd to the pyrrolo-pyrimidine (20), which was isolated by filtration. Reaction of (20) with phosphorous oxychloride ac reflux afforded the corresponding 4-chloro derivative (21) . Coupling of the chloro derivative with crans-4- aminocyclohexanol in DMSO at 135°C gave compound (18) f rom compound (21). Schemes II-VIII demonstrate that it is possible to functionalize the 5- and 6-position of the pyrrolopyrimidine ring. Through the use of different starting reagents and slight modifications of the above reaction schemes, various funcţional groups can be introduced at the 5- and S-positions in formula (I) and (II). Table 2 illustrates some examples. Table 2. Selected pyrrolopyrimidines.is of 5- and 6-substituted Starting Reagent (Figure Removed) A skilled artisan will know that metabolism of the compounds disclosed herein in a subject produces certain biologically active metabolites which can serve as drugs. The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. 11 should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. Prepara tion 1: A rnodification of the alkylation method of Seela and Lupke was used.1 To an ice-cooled (0°C) solution of ethyl cyanoacetate (6.58 g, 58.1 mmol) in -MeOH (20 mL) was slowly added a solution of NaOMe (25% w/v/ 58.1 mmol). After 10 min, chloroacetone (5 mL; 62.8 mmol) was slowly added. After 4 h, the solvent was removed. The brown oii was diluted the EtOAc (100 mL) and washed with H20 (100 mL) . The organic fraction was dried, filtered, and concentrated to a brown oii (7.79 g; 79%). The oii (3) (Scheme IV) was a mixture of methyl/ethyl ester products (9/1) , and was used without further purificat ion. 1H NMR (200 MHz, CDC13) 6_4.24 (q, J m 7.2 Hz, OCH2), 3.91 (dd, 1H, J* 7.2, 7.0 Hz, CH) , 3.62 (s, 3H, OCH3), 3.42 (dd, 1H, J- - 15.0, 7.1 Hz, l x CH2); 3.02 (dd, 1H, J * 15.0, 7.0 Hz, l x CH2); 2.44 (s, 3H, CH3) , 1.26 (t. j = 7.1 Hz, ester-CH3) . , F.; Lupke, U. Chem. Ber. 1977, no, 1462-1469. Prcparation 2: The procedure of Seela and Lupke was used. Thus, protection of the ketone (3) (Scheme IV; 5.0 g, 32.2 mmol) with ethylene glycol (4 mL, 64.4 mmol) in the presence of TsOH (100 mg) afforded (4) as an oii (Scheme IV; 5.2 g, 81.0) after flash chr ornat ography (SiO2; 3/7 EtOAc/Hex, Rf 0.35) . Still contains "5% ethyl ester: XH NMR (200 MHz, CDC13) 5_4.24 (q, J - 7.2 Hz, OCH2), 3.98 (s, 4H, 2 x acetal-CH2), 3.79 (s, 3H, OCH3) , 3.62 (dd, 1H, J * 7.2, 7.0 Hz, CH) , 2. 48 (dd, 1H, J - 15.0, 7.1 Hz. l X CH2), 2.32 (dd, 1H, J = 15.0, 7.0 Hz. l x CH2) ; 1.35 (s, 3H, CH3) , 1.26 (t, J- 7.1 Hz, ester-CH3); MS (ES) : 200.1 (M' + l) . '•Seela, F.; Lupke, D. Chem. Ber. 1977. 110. 1462-1469. Preparation 3: A solution of acetal (4) (Scheme IV, l g, 5.02 mmol! , bcnzamidine (786 mg, 5.02 mmol), and DBU (1.5 mL, 10.04 mmol) in dry DMF (15 mL) was heated to 85°C for 15 h. The mixture was diluted with CHC13 (30 mL) and washed with 0.5 N NaOH (10 mL) and H20 (20 mL) . The organic fraction was dried, filcered and concentrated to a brown oii. Flash chromacography (SiOi; 1/9 EtOAc/CH2Cl2, Rt 0.35) was accempced, but material crystallized on the column. The silica gel was washed with MeOH. Fractions containing the product (5) (Scheme IV) were concentrated and used without further purification (783 mg, 54.3*): LH NMR (200 MHz, CDC13) 6 8.24 (m, 2H, Ar-H), 7.45 (m, 3K, Ar-H), 5.24 (br s, 2H, NH2), 3.98 (s, 4H, 2 x acetal-CH2), 3.60-3.15 (m, 2H, CH2) , 1.38 (s, 3H, CH3) ; MS (ES) : 288.1 (M"+l). Preparation of compound (20) (Scheme VIII): A solution of acetal (19) (4.43 g, 20.6 mmol)1, benzamine hydrochloride (3.22 g, 20.6 mmol), and DBU (6.15 mL, 41.2 mmol) in dry DMF (20 mL) was heated to 85°C for fifteen hours. The mixture was diluted with lOOtnL of CHC1?, and washed with H:0 (2 x 50 mL) . The organic fraction was dried, filtered, and concentrated to a dark brown oii. The dark brown oii was stirred in IN HCl (100 mL) for 2 hours at room temperature. The resulting slurry was filtered yielding the HCl salt of (20) as a t an solid (3.60 g, 70.6*); *H NMR (200 MHz, DMSO-d6) 11.92 (s 1H) , 8.05 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 7.05 (s, 1H, pyrrole- H) ; MS(ES) : 212.1 (M' + l) . Preparation 4: A solution of acetal (5) (700 mg, 2.44 mmol) in l N HCl (40 mL) was stirred for 2 h at RT. The resultant slurry was filtered yielding the HCl salt of 2-phenyl-6-methyl-7H- pyrrolo [2, 3d] pyrimidin-4 (3H) -one as a tan solid (498 mg, 78.0%): :H NMR (200 MHz, DMSO-d6) 6 11.78 (s, 1H), 8.05 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 6.17 (s, 1H, pyrrole-H), 2.25 (s, 3H, CH3) ; MS (ES) : 226.1 (M*+l). Prepmration 5: A modification of the Chen ec al. cyclization method was used. To an ice-cooled (0°C) solucion of bromide (9), (Scheme V; 20.0 g, 108 mmol; 90% pure) in isopropyl alcohoi (60 mL) was slowly added a solution of a-methylber.zylamine (12.5 mL, 97.3 mmol). The black solucion was allowed to warm to RT and ştir for 15 h. The mixture was diluted with EtOAc (200 mL) and washed with 0.5 N NaOH (50 mL) . The organic fraction was dried, filtered, and concentrated co a black tar (19.2 g; 94%) . The residue was partially purified by flash chromatography (Si02; 4/96 MeOH/CH2Cl2, % 0.35) to a black solid (6.38 g, 31%) as the compound dl-l-(l-phenylethyl)-2- amino-3-cyano-4-methylpyrrole: MS (ES) : 226.1 (M"•*•!). :Chen, Y. L.; Mansbach, R. S.; Winter, S. M.; Brooks, E.; Collins, J.; Corman, M. L.; Dunaisîcis, A. R.; Faraci, W. S.; Gallaschun, R. J.; Schmidt, A.; Schulz, D. W. J. Med. Chem. 1997, 40, 1749-1754. Preparation 6: To a solution of dJ-l-(1-phenylethyl)-2-amino-3-cyano-4,5- dimechylpyrrole: (14.9 g, 62.5 mmol) and pyridine (10.0 mL) in dichloromethane (50.0 mL) was added benzoyl chloride (9.37 g, 66.7 mmol) at OiC. After stirring at 0°C for l hr, hexane (10.0 mL) was added to help precipitation of product. Solvent was removed in vacuo and the solid was recrystallized from EtOH/H:0 to give 13.9 g (65%) of d2-l- (1-phenylethyl) -2- phenylcarbonylamino-3-cyano-4, 5-dimethylpyrrole. mp 218-221°C; •H NMR (200 MHz, CDC1J 6_1.72 (s, 3H), 1.76 (d, J » 7.3 Hz. 3H), 1.98 (s, 3H), 5.52 (q, J = 7.3 Hz, 1H), 7.14-7.54 (m, 9H) , 7.6:8-7.72 (dd, J =* 1.4 Hz, 6.9 Hz , 2H) , 10.73 (s, 1HJ ; MS (ES) : 344.4 (M't-1) . '• Liebigs Ann. Chem. 1986, 1485-1505. The following compounds were obtained in a similar manner. Prepara t ion 6A: dl-1- (1-phenylethyl) -2- (3-pyridyl) carbonylamino-3-cyano-4 , 5- i dimethylpyrrole. :H NMR (200 MHz, CDCl,) 6_1.83 (d, J . 6.6 Hz. 3H) , 2.02 (s, 3H) , 2.12 (s, 3H) , 5.50 (q, J = 6.8 Hz, 1H) , 7.14-7.42 (m, 5H) , 8.08 (m, 2H) , 8.75 (m, 3H) ; MS (ES) : 345.2 dl-1- (1-phenylethyl) -2- (2-furyl) carbonylamino-3-cyano-4 , 5-dimethylpyrrole . :H NMR (200 MHz, CDC13) 6 l . 84 (d, J » 7.4 Hz, 3H) , 1-92 (s, 3H), 2.09 (s, 3H) , 5.49 (q, J m 7.4 Hz, 1H) , 6.54 (dd, J « 1.8 HZ, 3.6 Hz, 1H) , 7.12-7.47 (m, 7H) ; MS (ES) : 334.2 (M'+l) , 230.1. dl -l- (1-phenylethyl) -2- (3-furyl) carbonylamino-3-cyano-4, 5- dimethylpyrrole. :H NMR (200 MHz, CDCl,) 5 1.80 (d, J • 7 Hz 3H) , 1.89 (S, 3H) , 2.05 (s, 3H) , 5.48 (q, J = 7 Hz, 1H) , 6.59 (S, 1H) , 7.12-7.40 (m, 6H) , 7.93 (s, 1H) ; MS (ES) : 334.1 (M'+l) . 230.0. dl-1- (1-phenylethyl) -2-cyclopentylcarbonylamino-3-cyano-4, 5- dimethylpyrrole . ;H NMR (200 MHz, CDCl,) 6 l . 82 (d, J - 7.4 Hz, 3H) , 1,88 (s, 3H) . 2.05 (s, 3H) , 1.63-1.85 (m, 8H) , 2.63 (m, 1H) , 5.43 (q, .J - 7.4 Hz , 1H) , 6.52 (s. 1H) , 7.05-7.20 (m, 5H) ; MS (ES) : 336.3 (M' dl-1- (1-phenylethyl) -2- (2-thieyl) carbonylamino-3-cyano-4, 5- dimethylpyrrole, :H NMR (200 MHz. CDC1:.) 6 1.82 (d, J = 6.8 Hz, 3H) , 1.96 (s. 3H) , 2.09 (s, 3H) . 5.49 (q, J» 6.8 Hz, 1H) , 7.05-7.55 (m. 8H) ; MS (ES) : 350.1 (M'+l), 246.0. dl-1- (1-phenylethyl) -2- (3-thienyl) carbonylamino-3 -cyano-4 , 5- dimethylpyrrole . •H NMR (200 MHz. CDCl,) 6 1.83 (d. J - 7.0 Hz, 3H) , 1.99 (s, 3H) , 2.12 (s, 3H) , 5.49 (q, J - 7.0 Hz. 1H) , 6.90 (m, 1H) , 7.18-7.36 (m, 6H) , 7.79 (m, 1H) ; MS (ES) : 350.2 (M'+l). 246.1. dl-1- (1-phenylethyl)-2-(4-fluorophenyl)carbonylamino-3-cyano-4,5-dimethylpyrrole. :H NMR (200 MHZ, CDCl,) 6 1.83 (d, J = 7.4 Hz, 3H) , 1.96 (s, 3H), 2.08 (S, 3H) , 5.51 (q, J = 7.4 Hz, 1H), 7.15-7.55 (m, 9H) ; MS (ES) : 362.2 (M'+l), 258.1. d2-l- (1-phenylethyl) -2- (3-fluorophenyl)carbonylamino-3-cyano-4,5-dimechylpyrrcle. :H NMR (200 MHz, CDCl,) 6 1.83 (d, J - 7.4 Hz 3H) , 1.97 (s, 3H) , 2.10(S, 3H) , 5.50 (q, J » 7.4 Hz, 1H) , 7.05-7.38 (m, 7 H), 7.67-7.74 (m, 2H); MS (ES): 362.2 (*T + 1), 258.1. dJ-1- (1-phenylethyl)-2-(2-fluorophenyl)carbonylamino-3-cyano- 4,5-dimethylpyrrole. :H NMR (200 MHz, CDC1J 6 1.85 (d, J = 7.2 Hz, 3H), 1.94 (s, 3H) , 2.11 (s, 3H), 5.50 (q, J = 7.2 hz, 1H) , 7.12-7.35 (m, 6H) , 7.53 (m, 1H) , 7.77 (m, 1H) , 8.13 (m, 1H) ; MS (ES) : 362 . 2 (M'+l) , 258.0. dl-l- (1-phenylethyl)-2-isoproylcarbonylamino-3-cyano-4,5- dimethylpyrrole.:H NMR (200 MHz, CDCl,) 6 1.19 (d, J - 7.0 Hz, 6H) , 1.82(d, J * 7.2 Hz, 3H) , 1.88 (s, 3H), 2.06 (s, 3H), 2.46 (m, 1H), 5.39 (m, J « 7.2 Hz, 1H), 6.64 (s. 1HJ, 7.11-7.36 (m, 5H) ; MS (ES) : 310.2 (M%1), 206.1 . In the case of acylation of dJ-l-(1-phenylethyl)-2-amino-3-cyano-4-methylpyrrole, monoacylated 'dl-1- (l-phenylethyl) -2-benzoylamino-3-cyano-4-dimethylpyrrole and diacylated pyrrole d2-l- (1-phenylethyl) -2-dibenzoylamino-3-cyano-4-methylpyrrole were obtained. Monoacylated pyrrole: H NMR (200 MHz, CDCl3) 6_7.69 (d, 2H, J = 7.8 Hz, Ar-H), 7.58-7.12 (m, 8H, Ar-H), 6.18 (s, 1H, pyrrole-H) , 5.52 (q, 1H, J * 7.2 Hz, CH-CH3) , [ 2.05 (s, 3H, pyrrole - CH3), 1.85 (d, 3H, J= 7.2 Hz, CH-CH3) ; MS (ES) : 330.2 (M'-t-l) ; Diacylated pyrrole: 'H NMR (200 MHz, CDC13) 5_7.85 (d, 2H, J - 7.7 Hz, Ar-H), 7.74 (d, 2H, J = 7.8 Hz, Ar-H), 7.52-7.20 (m, 9H, Ar-H), 7.04 (m, 2H, Ar-H), 6.21 (s, 1H, pyrrole-H) , 5.52 (q, 1H, J« 7.2 Hz, CH-CH3) , 1.77 (d, 3H, J- 7.2 Hz, CH-CH3), 1.74 (s, 3H, pyrrole-CH3) ; MS iES; : 434.1 (M%1). Preparation 7: To a solution of dl-l-(1-phenylethyl)-2-phenylcarboxyamido-3- cyano-4,5-dimethylpyrrole (1.0 g, 2.92 mmol) in methanol (10.0 mL) was added concentrated sulfuric acid (l. O mL) az 0°C. The resulced mixcure was refluxed for 15 hr and cooled down to room temperature. The precipitate was filtered to give 0.48 g (48%) of dI-5,6-dimethyl-2-phenyl-7tf-7-(i- phenylethyl)pyrrolo[2,3d]pyriraidin-4(3H)-one. :H NMR (200 MHz, CDC13) 5_2.02 (d, J - 7.4 Hz, 3H) , 2.04 (s, 3H) , 2.41 (s, 3H) . 6.25 dI-5,6-dimethyl-2-(3-pyridyl)-7H-7-(1-phenylethyl) pyrrolo[2,3d]pyrimidin-4(3H)-one. *H NMR {200 MHz, CDC13) 5_2.03 (d, J • 7.2 Hz, 3H) , 2.08 (s, 3H), 2.42 (s, 3H) , 6.24 (q, J = 7.2 Hz, 1H), 7.09-7.42 (m, 5H) , 8.48 (m, 2H) , 8.70 (m, 3H); MS (ES): 345.1 (M'+l). di-5, 6-dimethyl-2- (2-furyl) -7H-7- (1-phenylethyl) pyrrolo[2,3d]pyrimidin-4 (3H)-one. 'H .NMR (200 MHz, CDC13) 6 1.98 (d, J » 7.8 Hz, 3H) , 1.99 (s, 3H) , 2.37 (s, 3H), 6.12 (q, J « 7.8 Hz, 1H), 6.48 (dd, Jl.8 Hz, 3.6 Hz, 1H), 7.17-7.55 (m, 7H) , 9.6 (s. 1H) ; MS (ES) : 334.2 (M't-1). dJ-5,6-dimethyl-2-{3-furyl)-7H-7-{l-phenylethyl)pyrrolo [2,3d]pyrimidin-4(3H)-one. ;H NMR (200 MHz, CDC1») 6 1.99 (d, J . 7 Hz, 3H) , 2.02 (s, 3H) , 2.42 (s, 3H) , 6.24 (q, J - 7 Hz, 1H) , 7.09 (s, 1H) , 7.18-7.32 (m, 5H) , 7.48 (S, 1H) , 8.51 (s, 1H) ; MS (ES! : 334.2 (M' + l) . dl-5,6-dimethyl-2-cyclopentyl-7H-7-(1-phenylethyl) pyrrolo[2,3d]pyrimidin-4 (3tf) -one. :H NMR (200 MHz, CDC1-.} 5 1.95 (d, J » 7.4 Hz, 3H), 2.00 (s, 3H) , 2.33 (s, 3K) , 1.66-1.88 (m, 8H) , 2.97 (m, 1H), 6.10 (g, J « 7.4 Hz, 1H), 7.16-7.30 (m, 5H) , .9.29 (s, 1H) ; MS (ES) : 336.3 (M' + l). dJ-5,S-dimethyl-2-(2-thienyl)-7H-7-(1-phenylethyl) pyrrolo[2,3d]pyrimidin-4 (3#) -one. ;H NMR (200 MHz, CDCl J 5 2.02(d, J * 7.2 HZ, 3H), 2.06 (s, 3H) , 2.41 (s, 3K), 6.13 (q, J = 7.2 Hz, 1H), 7.12 (dd, J = 4.8, 2.8 Hz, 1H), 7.26-7.32 (m, 5H) , 7.44 (d, J * 4.8 Hz, 1H) , 8.01 (d, J = 2.8 Hz, 1H) 11.25 (s, 1H); MS (ES): 350.2 (M'+l). dl-5 , 6-dinte t hy 1-2- (3-thienyl) -7H-7- (l-phenylechyl) pyrrolo[2,3d]pyrimidin-4 (3tf) -one. 'H NMR (200 MHz, CDCl,) 6 2.00 (d, J» 7.4 Hz, 3H), 2.05 (s, 3H) , 2.43 (S, 3H), 6.24(q, J » 7.4 Hz, 1H), 7.24-7.33 (m, 5H) , 7.33-7.39 (m, 1H) , 7.85 (m, 1H), 8.47 (m, 1H), 12.01 (s, 1H); MS (ES): 350.2 (M*+l). dl-5,6-dimethyl-2-(4-fluorophenyl)-7H-7-(1-phenylethyl) pyrrolo[2,3d]pyrimidin-4 (3H) -one. :H NMR (200 MHz, CDCl,) 5 2.01 (d, J » 6.8 Hz, 3H), 2.05 (s, 3H) , 2.42 (s, 3H), 6.26 (q, J = 6.8 Hz, 1H) , 7.12-7.36 (m, 7H), 8.23-8.30 (m, 2H) , 11.82 (s, 1H) ; MS (ES) : 362.3 (M'-t-l) . dl-5,6-dimethyl-2-(3-fluorophenyl)-7H-7-(1-phenylethyl) pyrrolo[2,3dJpyrimidin-4 (3#)-one. ;H NMR (200 MHz, CDCl,) 5 2.02 (d, J » 7.4 HZ, 3H), 2.06 (s, 3H), 2.44 (s, 3H), 6.29 (q, J - 7.4 Hz, 1H) , 7.13-7.51 (m, 7H) , 8.00-8.04 (m, 2H) , 11.72 (s, 1H); MS (ES): 362.2 (M*+l). dl-5,6-dimechyl-2-(2-fluorophenyl)-7H-7-(l-pjhenylethyl) pyrrolo[2,3d]pyrimidin-4 (3H)-one. 'H NMR (200 MHz, CDC1;) 6 2.00(d, J - 7.2 Hz, 3H), 2.05 (s, 3H), 2.38 (s, 3H), 6.24 (q, J « 7.2 Hz, 1H), 7.18 - 7.45 (m, 8 H), 8.21 (m, 1H), 9.54 (s, 1H) ; MS (ES) : 362.2 (M' + l) . dJ-5, 6-dimethyl-2-isopropyl-7tf-7-(1-phenylerhyl)pyrrclc [2, 3d] pyrimidin-4 (3#) -one. :H NMR (200 MHz, CDC13) 6 1.30 (d, J = 6.8 Hz, 3H) , 1.32 (c, J « 7.0 H2, 3H) , 2.01 (s, 3H) , 2.34 (s, 3H). 2.90 (m, 1H) , 6.13 (m, 1H) , 7.17-7.34 (m, 5H) , 10.16 (s, 1H) ; MS (ES) : 310.2 (M'*l) . Preparation 8: A solution of dl-l- (l-phenylethyl) -2-benzoylamino-3-cyano-4-dimethylpyrrole (785 mg, 2.38 mmol) with concentrated H?S04 (l mL) in DMF (13 mL) was stirred at 130°C for 48 h. The blacfc solution was diluted with CHC13 (100 mL) and washed with l N NaOH (30 mL) , and farine (30 mL) . The organic fraction was dricd, filtered, concentrated, and purified by flash chromatography {SiC>2; 8/2 EtOAc/Hex, R* 0.35) to a brown solid (184 mg, 24%) as dl-5-methyl-2-phenyl-7#-7- (1-phenylethyl)pyrrolo [2, 3d]pyrimidin-4 (3H)-one. 1H NMR (200 MHz, CDC13) 6_8.18 (m, 2H, Ar-H), 7.62-7.44 (m, 3H, Ar-H). 7.40-7.18 (m, 5H, Ar-H), 6.48 (s, 1H, pyrrole-H), 6.28 (q, 1H, J - 7.2 Hz. CH-CH3) , 2.18 (s, 3H, pyrrole-CH3) , 2.07 (d, 3H, J = 7.2 Hz. CH-CH3); MS (SS) : 330.2 (M* * 1). Fraparătion 9: A mixture of dl-l-(1-phenylethyl)-2-amino-3-cyano-4,5- dimethylpyrrole (9.60 g, 40.0 mmol) and of formic acid (50.0 mL, 98%) was refluxed for 5 hr. After cooling down to room teraperature and scratching the sides of flask, copious precipitate was formed and filtered. The material was washed with water until washings showed neutral pH to give dl-5,6- dimethyl-7H-7-(1-phenylethyl)pyrrolo[2,3d]pyrimidin-4(3H) - one. :H NMR (200 MHz, CDC13) 5 1.96 (d, J - 7.4 hz, 3H) , 2.00 (S, 3H), 2.38 (S, 3H), 6.21 (q, J - 7.4 Hz, 1H), 7.11-7.35 (m, 5H) , 7.81 (S, 1H) , 11.71 (s, 1H) ; MS (ES) : 268.2 (M'-t-l). Preparation 10: dl-5, 6-dimethyl-2-phenyl-7#-7- (l-phenylethyl) pyrroic [2, 3d] pyrimidin-4 (3 H) -one (l. o g, 2.91 mmol) was suspended ir. polyphosphoric acid (30.0 mL) . The mixture was heated ac 100;C for 4 hr. The hoţ suspension was poured onto i ce water, stirred vigorously to disperse suspension, and basified to pK 6 with solid KOH. The resulting solid was filtered and collected to give 0.49 g (69%) of 5,6-dimethyl-2-phenyl-7j?-pyrrolo [2, 3d] pyrimidin-4 (3#) -one. ;H NMR (200 MHz, DMSO-dr) 6_2.17 (s, 3H), 2.22 (s, 3H) , 7.45 (br. 3H) , 8.07 (br, 2H. ) . 11.49 (S, 1H) , 11.82 (s, 1H) ; MS (ES) : 344.2 (M' + l). The following compounds were obtained in a similar manner as that of Preparation 10: 5-methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidin-4 (3H) -one. MS (ES) : 226.0 (M'+l) . 5, 6-dimethyl-2- (3-pyridyl) -7tf-pyrrolo [2, 3d] pyrimidin-4 (3H) -one. MS (ES) : 241.1 (M't-1) . 5,6-dimethyl-2- (2-furyl) -7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one. :H NMR (200 MHz, DMSO-ds) 6 2.13 (s, 3H) , 2.18 (s, 3H) , 6.39 (dd, J - 1.8, 3.6 Hz, 1H) , 6.65 (dd, J - 1.8 Hz, 3.6 Hz, 1H) , 7.85 (dd, J * 1.8, 3.6 Hz, 1H, ) , 11.45 (S, 1H) , 11.60 (s, 1H) ; MS (ES) : 230.1 (M*+l) . 5, 6-dimethyl-2- (3-furyl) -7tf-pyrrolo [2 , 3d] pyrimidin-4 (3/f) -one. ;H NMR (200 MHz, DMSO-dt) 6 2.14 (s, 3H) , 2.19 (s, 3H) , 6.66 (s, 1H) , 7.78 (s, 1H) . 8.35 (s, 1H) , 11.3 (s, 1H) , 11.4 (s, 1H) ; MS (ES) : 230.1 (M"+l) . 5 , 6-dimethyl-2-cyclopentyl-7-pyrrolo [2, 3d] pyrimidin-4 one. :H NMR (200 MHz, DMSO-dJ 5 1.57-1.91 (m, 8 H), 2.12 (s, 3H) , 2.16 (s, 3H) , 2.99 (m, 1H) , 11.24 (s, 1H) , 11.38 (s, 1H) ; MS (ES) : 232.2 (M' + D . 5,6-dimethyl-2- (2-thienyl) -7H-pyrrolo [2, 3d]pyrimidir.-4 (3H) -one. ;H NMR (200 MHZ, DMSO-ds) 6 2.14 (s, 3H) , 2.19 (s, 3K) , 7.14 (dd, J » 3.0, 5.2 Hz, 1H) , 7.70 (d. J = 5.2 Hz 1H), 8.10 (d, J-3.0 Hz, 1H), 11.50 (s, 1H); MS (ES): 24S.1 (M'+l). 5,S-dimethyl-2- (3-thienyl) -7ff-pyrrolo[2, 3d]pyrimidin-4 (3#) -one. :H NMR (200 MHz, DMSO-d«) 6 2.17 (s, 3H) , 2.21 (s, 3H) , 7.66(m, 1H), 7.75 (m, 1H) , 8.43 (m, 1H), 11.47 (s, 1H), 11.69 (S, 1H) ; MS (ES) : 24S.1 (M* + l) . 5, 6~dimethyl-2- (4-fluorophenyl) -7ff-pyrrolo [2, 3d]pyrimidin-4(3H)-one. 'H NMR (200 MHz, DMSO-d«) 6 2.17 (s, 3H) , 2.21 (s, 3H) , 7.31 (m, 2H) , 8.12 (m, 2H) , 11.47 (s, 1H) ; MS (ES) : 258.2 (M*+l). S, 6-dimethyl-2-(3-fluorophenyl)-7H-pyrrolo 12,3d]pyrimidin-4(3H)-one. 1H NMR (200 MHz, DMSO-d«) 6 2.18 (s, 3H) , 2.21 (s, 3H), 7.33 (m, 1H), 7.52 (m, 1H) , 7.85-7.95 (m, 2H) , 11.56 (s, 1H), 11.80 (S, 1H); MS (ES): 258.1 (M*+l). 5, 6-dimethyl-2- (2-f luorophenyl) -7H-pyrrolo 12, 3d] pyrimidin-4(3tf)-one. :H NMR (200 MHz, DMSO-dJ 6 2.18 (s, 3H) , 2.22 (s, 3H) , 7.27-7.37 (m, 2H) , 7.53 (m 1H) , 7.68 (m, 1H) , 11.54 (s, 1H), 11.78 (S, 1H); MS (ES): 258.1 (M'+l). 5, 6-dimethyl-2-isopropyl-7H-pyrrolo[2,3d]pyrimidin-4 (3H) -one. :H NMR (200 MHz, DMSO-d«) 5 1.17 (d, J« 6.6 Hz, 6H) , 2.11 (s, 3H) , 2.15 (S, 3H) , 2.81 (m, 1H) , 11.20 (s, 1H) , 11.39 (s, 1H) ; MS (ES) : 206.1 (M' + l) . 5, 6-dimethyl-7tf-pyrrolo [2, 3d] pyrimidin-4 (3H) -one . ;H NMR (200 MHz, DMSO-dJ 5 2.13 (s, 3H), 2.17 (s, 3H), 7.65 (s, 1H); MS (ES) : 164.0 (M'-t-U . Preparation 11: A solution of 5,6-dimethyl-2-phenyl-7tf-pyrrolo[2,3d] pyrimidin-4 (3tf) -one (1.0 g, 4.2 înmoi) in phosphorus oxychloride (25.0 mL) was refluxed for 6 hr and ther. concentraced in vacuo to dryness. Water was added to che residue co induce crystallization and the resulting solid was filtered and collected Co give 0.90 g (83%) of 4-chloro-5, 6-ditnethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, DMSO-ds) 6_2.33 (s, 3H) , 2.33 (s, 3H) . 7.46-7.49 (m, 3H) , 8.30-8.35 (m, 2H) , 12.20 (s, 1H); MS (ES): 258.1 (M'+l). The following compounds were obtained in a similar manner as that of Preparation 11: 4-chloro-5-methyl-2-phenyl-7H-pyrrolo[2, 3d]pyrimidine. MS (ES) : 244.0 (M'+l) . 4 -chloro-6-methyl- 2-phenyl-7H-pyrrolo[2, 3dJ pyrimidine. MS (ES) : 244.0 (M*+l) . 4-chloro-2-phenyl-7tf-pyrrolo[2,3d]pyrimidine. ;H NMR (200 MHz, DMSO-d6) 8.35 (2, 2H) , 7.63 (br s, 1H) . 7.45 (m, 3H), 6.47 (br s, 1H) ; MS (ES) : 230.0 (M%1) . 4-chloro-5,6-dimethyl-2- (3-pyridyl)-7H-pyrrolo[2, 3d] pyrimidine. MS (ES) : 259.0 (M'-cl) . 4 -chloro-5, 6-dimethyl-2- (2-furyl) -7H;pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHz, DMSO-dJ 6 2.35 (s, 3H) , 2.35 (s, 3H) , 6.68 (dd, J - 1.8, 3.6 Hz, 1H) , 7.34 (dd, J - 1.8 Hz, 3.6 Hz, 1H) , 7.89 (dd, J 1.8. 3.6 HZ, 1H); MS (ES): 248.0 (M'+l). 4 -chloro-5. 6-dimethyl-2- (3-furyl) -7/f-pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHZ, DMSO-d») 6 2.31 (s, 3H) , 2.31 (s, 3H) , 6.62 (S, 1H) , 7.78 (s, 1H) . 8.18 (s, 1H) , 12.02 (s, 1H) ; MS (ES) : 248.1 (M*+l). 4-chloro-5,6-dimethyl-2-cyclopentyl-7-pyrrolo[2,3d] pyrimidine. 'H NMR (200 MHz, DMSO-d«) 6 1.61- 1.96 (m, 8H) , 2.27 (s, 3H) , 2.27 (s, 3H) , 3.22 (m. 1H) , 11.57 (s, 1K) ; KS (ES) : 250.1 (M' + l) . 4 -chloro-5, 6-dimethyl-2- (2-thienyl) -7AT-pyrrolo [2 , 3d] pyrimidine. :H NMR (200 MHz, DMSO-dJ 6 2.25 (s, 3H) . 2.31 (s. 3H), 7.14 (dd, J = 3.1 Hz, 4.0 Hz , 1H) , 7.33 (d, J = 4 . 9 Hz , 1H) , 7.82 (d, J = 3.1 Hz, 1H) , 12.19 (s, 1H) ; MS (ES) : 264.1 (M* -ci) . 4-chloro-5, S-dimethyl-2- {3-thienyl) -7#-pyrrolo [2 , 3 d] pyrimidine. :H NMR (200 MHz, DMSO-ds) 6 2.32 (s, 3H) , 2.32 (s, 3H), 7.62 (dd, J - 3.0, 5.2 Hz, 1H) , 7.75 (d, J = 5.2 Hz, 1H) , 8.20 (d, J = 3.0 Hz, 1H) ; MS (ES) : 264.0 (M'+l) . 4-chloro-5, 6-dimethyl-2- (4 -f luorophenyl) -7H-pyrrolo [2,3d] pyrimidine. ;H NMR (200 MHz, DMSO-d«) 6 2. 33 (s, 3H) , 2.33 (s, 3H) , 7.30 (m, 2H) , 8.34 (m, 2H) , 12.11 (s, 1H) ; MS (ES) : 276.1- (M' -t-1) . 4-chloro-5, 6-dimethyl-2- (3 -f luorophenyl) -7H-pyrrolo [2, 3d] pyrimidine. aH NMR (200 MHz, DMSO-dJ 5 2. 31 (s, 3H) , 2.33 (s, 3H) , 7. 29 (m, 1H) , 7.52 (m, 1H) , 7.96 (m, 1H) , 8. 14 (m, 1H) , 11.57 (s, 1H) ; MS (ES) : 276.1 (M'+l) . 4-chloro-5, 6-dimethyl-2- (2-fluorophenyl) -7tf-pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHz, DMSO-ds) 6 2.34 (s, 3H) , 2.34 (s, 3H) , 7.33 (m, 2H) , 7.44 (m, 1H) , 7.99 (m, 1H) , 12.23 (s, 1H) ; MS (ES) : 276.1 (M' l-chloro-5 , 6-dimethyl-2-isopropyl-7#-pyrrolo [2, 3d] pyrimidine. H NMR (200 MHz, DMSO-dJ 6 1.24 (d, J - 6.6 Hz, 6H) , 2.28 (s, 3H) , 2.28 (s, 3H) , 3.08 (q, J = 6.6 Hz, 1H) , 11.95 (s, 1H) ; ÎS (ES) : 224.0 (M*+l) . i-chloro-5, 6-dimechyl-7H-pyrrolo [2, 3d] pyrimidine . JH NMR (200 MHz, DMSO-dJ 6 2.31 (s, 3H) , 2.32 (s, 3H) , 8.40 (s, 1H) ; ÎS (ES) : 182.0 (M" + l) . dI-4-chloro-5,6-dimethyl-2-phenyl-7#-7- (i-phenylethyDpyrrclc [2,3d]pyrimidine. Preparation 12: To a solution of dl-l,2-diaminopropane (1.48 g, 20.0 mmol) and sodium carbonate (2.73 g, 22.0 mmol) in dioxane (100.0 mL) and water (100.0 mL) was added di-cerc-dicarbonate (4.80 g, 22.0 mmol) ac room temperatura. The resultec mixture was stirred for 14 hr. Dioxane was removed in vacuo. The precipitate was filtered off and the filtrate was concentrated in vacuo to dryness. The residue was triturated with EtOAc and then filtered. The filtrate was concentrated in vacuo to dryness to give a mixture of dl-l-amino-2-(l,1-dimethylethoxy) carbonylamino-propane and o?2-2-amino-l-(l, 1- dimethylethoxy) carbonylamino-propane which were not separable by normal chromatography method. The mixture was used for the reaction in Example 8. Fraparătion 13: To solution of Fmoc-3-Ala-OH (1.0 g, 3.212 mmol) and oxalyl chloride (0.428 g, 0.29 mL, 3.373 mmol) in dichloromethane (20.0 mL) was added a few drops of N,N-dimethylformamide at 0°C. The mixture was stirred at room temperature for l hr followed by addition of cyclopropylmethylamine (0.229 g, 0.28 mL, 3.212 mmol) and triethylamine (0.65 g, 0.90 mL, 6.424 mmol) . After 10 min, the mixture was treated wich l M hydrochloride (10.0 mL) and the aqueous mixture was extracted with dichloromethane (3 x 30.0 mL) . The organic solution was concentrated in vacuo to dryness. The residue was treated with a solution of 20% piperidine in N,N-dimethylforamide (20.0jmL) for 0.5 hr. After removal of the solvent in vacuo, the residue was treated with l M hydrochloride (20.0 mL) and ethyl acetate (20.0 mL) . The mixture was separated and the aqueous layer was basified with solid sodium hydroxide to pH = 8. The precipitate was removed by filtration and the aqueous solution was subjected to ion exchange column eluted with 20% pyridine to give 0.262 g (57%; cf N-cyclopropylmethyl 3-alanine amide. :K NMR (200 MHz, CD-.OZ] 6_0.22 (m, 2H) , 0.49 (m, 2H) , 0.9S (m, 2H) , 2.40 (c, 2K) . 2.92 (t, 2H), 3.05 (d, 2H); MS (ES): 143.1 (M'+l). Prcparation 14: N- cert-butoxycarbonyl- crans-1,4-cyclohexyldiamine. trans-1,4-cyclonexyldiamine (6.08 g, 53.2 mmol) was dissolved in dichloromethane (lOOmL) . A solution of di-t-butyldicarbonate (2.32 g, 10.65 mmol in 40 mL dichloromethane) was added via cannula. After 20 hours, the reaction was partitioned between CHC1, and water. The layers were separated and the agueous layer was extracted with CHCl, (3x) . The combined organic layers were dried over MgSO«, filtered and concentrated to yield 1.20 g of a white solid (53V). :H-NMR (200MH2, CDC13) : 6 1.0-1.3 (m. 4H) , 1.44 (s, 9H), 1.8 -2.1 (m, 4H), 2.62 (brm, 1H), 3.40 (brs, 1H), 4.37 (brs, 1HO; MS (ES) : 215.2 (M'-t-l) . 4- (N-acetyl) -N- cert-butoxycarbonyl- crans-1, 4 -cyclohexyl diamine. N-Cert-butoxycarbonyl-trans-1,4-cyclohexyldiamine (530 mg, 2.47 mmol) was dissolved in dichloromethane (20 mL) . Acetic anhydride (250 mg, 2.60 mmol) was added dropwise. After 16 hours, the reaction was diluted with water and CHC13. The layers were separated and the aqueous layer was extracted with CHClş (3x). The combined organic layers were dried over MgS04, filtered and concentrated. Recrystallization (EtOH/%0) yielded 190 mg of white crystals (30%) . 'H NMR (200 MHz, CDClj) : 5 0.9 - 1.30 (m, 4H) , 1.43 (s, 9H) , 1.96-2.10 (m, 7H), 3.40 (brs, 1H), 3.70 (brs, 1H) , 4.40 (brs, 1H) , 4.40 (brs. 1H); MS (ES): 257.2 (M'+l), 242.1 (M" - 15), 201-1 (M" - 56). 4 -(4-crans-acetamidocyclohexyl)amino-5,6-dimethyl-2-phenyl- 7H-(1-phenylethyl) pyrrolo[2,3d]pyrimidine. 4-(N-acetyl)-N-cerc-butoxycarbonyl-crans-1,4- cyclohexyldiamins (190 mg, 0.74 mmol) , was dissoived ir. dichloromethane (5 raL) and diluted wich TFA (6 ml) . After 16 hours, che reaction was concencrated. The crude solid, DMSC (2mL), NaHCO, (200 mg, 2.2 mmol) and 4-chloro-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine (35 mg, 0.14 mmol) were comJbined in a flask and hcated to 130 °C. After 4.5 hours, che reaction was cooled to room temperature and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc (3x). The combined organic layers were dried over MgS04, filtered and concentrated. Chromatography (silica preparatory plate; 20:1 CHC1:. :EtOH) yielded 0.3 mg of a t an solid (1% yield) . MS (ES) : 378.2 (M'+l) . 4 -(N-methanesulfonyl)-N-Cerc-butoxycarbonyl-crans-1,4- cyclohexyldiamine. crans-l,4-cyclohexyldiamine (530 mg, 2.47 mmol) was dissoived in dichloromethane (20 ml) and diluted with pyridine (233 mg, 3.0 mmol). Methanesulfonyl chloride (300 mg, 2.60 mmol) was added dropwise. After 16 hours, the reaction was diluted with water and CHC1:.. The layers were separated and the aqueous layer was extracted with CHC13 (3x). The combined organic layers were dried over MgSO«, filtered and concentrated. recrystallization (EtOH/H?0) yielded 206 mg of white crystals (29%). ;H-NMR (200MHZ, CDC13) : 6 1.10-1.40 (m, 4H) , 1.45 (s, 9H). 2.00-2.20 (m, 4H) , 2.98 (s, 3H) , 3.20-3.50 (brs, 2H) . 4.37 (brs, 1H) ; MS (ES) 293.1 (NT+1) . 278.1 W-15) , 237.1 (M'-56) . 4- (4- crans-methanesulfatnidocyclohexyl)amino-5, 6-dimethyl-2- phenyl-7H- (1-phenylethyl) pyrrolo (2, 3d] pyrimidine . 4- (N-sulfonyl) -N-cert-butoxycarbonyl-crans-1,4- cyclohexyldiamine (206 mg, 0.71 mmol), was dissoived in dichloromethane (5ml) and diluted with TFA (6 ml) . After 16 hours, the reaction was concentrated. The crude reaction mixture, DMSO (2 ml), NaHC03 (100 mg, 1.1 mmol) and 1-chloro- 5 , 6-dimethyl -2 -phenyl- 7H-pyrrolo ( 2 , 3d] pyrimidine were combined in a flask and heaced to 130 °C. After 15 hours, rhe reaction was cooled to room temperature, and diiuted witr. EtOAc (3x). The combined organic layers were dried over MgS04, filtered and concentrated. Chromacography (silica preparatory plate, 20:1 CHCl3/EtOH) yielded 2.6 mg of a tan solid (5* yield). MS (ES): 414.2 (M'+l). Exajnple 1: A solution of 4-chloro-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d] pyrimidine (0.50 g, 1.94 mmol) and 4-crans-hydroxy cyclohexyl amine (2.23 g, 19.4 mmol) in methyl sulf oxide (10.0 tnL) was heated ac 130°C for 5 hr. After cooling down to room temperature, water (10.0 mL) was added and the rasulted aqueous solution was extracted with EtOAc (3 xlO.O mL) . The combined EtOAc solution was dried (MgSO«) and filtered, the filtrate was concentrated ia vacuo to dryness, the residue was chromatographed on silica gel to give 0.49 g (75%) of 4-(4-crans-hydroxycyclohexyl)amino-5,6-dimethyl-2-phenyl-7H- pyrrolo [2,3d]pyrimidine. mp 197-199°C; :H NMR (200 MHz, CDC13) 6_1.25-1.59 (m, 8H), 2.08 (s, 3H) , 2.29 (s, 3H), 3.68-3.79 (m, 1H), 4.32-4.38 (m, 1H), 4.88 (d, J - 8 Hz, 1H), 7.26-7.49 (m, 3H) , 8.40-8.44 (dd, J = 2.2, 8 Hz, 2H) , 10.60 (s, 1H) ; MS (ES) : 337.2 (M' + l) . The following compounds were obtained in a similar manner to that of Example l: 4- (4-trans-hydroxycyclohexyl)amino-6-methyl-2-phenyl-7H- pyrrolo[2,3d]pyrimidine.XH NMR (200 MHz, CDC13) 6_11.37 (s, 1H, pyrrole-NH) , 8.45 (m, 2H, Ar-H), 7.55 (m, 3H, Ar-H), 6.17 (s, 1H, pyrrole-H) , 4.90 (br d, 1H, NH) , 4.18 (m, 1H, CH-0) , 3.69 (m, 1H, CH-N) , 2.40-2.20 (m, 2H) , 2.19-1.98 (m, 2H) , 2.25 (S, 3H. CH3) 1.68-1.20 (m, 4H); MS (ES): 323.2 (M'+l). 4 - (4 - crans-hydroxycyclohexyl) amino- 5-methyl - 2 -phenyl-7/f- pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, CDC13) 6_11.37 (s, 1H, pyrrole-NH), 8.40 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 5.96 (s, 1K, pyrrole-H) , 4.90 (br d. 1H, NH) , 4.18 (m, 1K, CK-C), 3.69 (m, 1H, CK-N) , 2.38-2.20 (m, 2H) , 2.18-1.98 (m, 2H) , 2.00 (S, 3H, CH3) 1.68-1.20 (m, 4H); MS (ES): 323.2 (M'+l). 4- (4- crans-hydroxycyclohexyl) amino-2-phenyi-7H-pyrrolo [2, 3d] pyritnidine. mp 245.5-246.5°C; :H NMR (200MHz, CD;OD) 6 8.33(m, 2H, Ar-H) , 7.42 (m, 3H, Ar-H) , 7.02 (d, 1H, J=3.6 Hz. pyrolle-H). 6.53 (d, 1H, J=3.6 Hz, pyrolle-H), 4.26 (m, 1H, CH-0), 3.62 (m,lH, CH-N) , 2.30-2.12 (m, 2H) . 2.12-1.96 (m, 2H) , 1.64-1.34 (m, 4H) ; MS, M+l-309.3; Anal (Ci?H:,N,0) C, H, N. 4 -(4 -Crans-hydroxycyclohexyl)amino-5,6-dimethyl-2-(3-pyridyl)-7#-pyrrolo[2,3d]pyrimidine. ;H NMR (200 MHz, CDC1J 6_1.21-1.54 (m, 8H) ; 2.28 (s, 3H) ; 2.33 (s, 3H) ; 3.70 (m, 1H) , 4.31(m. 1H) , 4.89 (d, 1H) , 7.40 (m, 1H). 8.61 (m, 2H), 9.64 (m, 1H) ; MS (ES) : 338.2 (M'-cl) . 4- (4-crans-hydroxycyclohexyl)amino-5,6-dimethyl-2- (2-furyl) -7H-pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz, CDC13) 6 1.26- 1.64(m, 8H), 2.22 (s. 3H). 2.30 (s, 3H), 3.72(m, 1H), 4.23 (m, 1H) , 4.85 (d, 1H) , 6.52(m, 1H) , 7.12 (m, 1H) , 7.53 (tn, 1H) , 9.28 (s, 1H) ; MS (ES): 327.2 (M%1) . 4- (4- trans-hydroxycyclohexyl) amino-5, 6-dimethyl-2- (3-furyl) -7H-pyrrolo[2,3d]pyrimidine. ;H NMR (200 MHz, CDClj) 6 1.25- 1.63 (m, 8 H), 2.11 (s, 3H), 2.27 (s, 3H), 3.71(m, 1H), 4.20 (m, 1H) , 4.84 (d, 1H) , 7.03 (m, 1H) , 7.45 (m, 1H) , 8.13 (m, 1H), 10.38 (m, 1H); MS (ES): 327.2 (M'+l). 4- (4-Crans-hydroxycyclohexyl)amino-5,6-dimethyl- 2 -cyclopentyl-7tf-pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, CDC1J 6 1.26-2.04 (m, 16 H), 2.26 (s, 3H) , 2.27 (s, 3H) , 3.15 (m, 1H) . 3.70 (m. 1H) , 4.12 (m, 1H) , 4.75 (d, 1H) ; MS (ES): 329.2 (M'+l). 4- (4-crans-hydroxycyclohexyl)amino-5, 6-dimethyl-2- (2-rhienyl! -7H-pyrrolo[2,3d]pyrimidin-4-amine. :H NMR (200 MHz, CDCi,) î 1.28-1.59 (m, 8H), 2.19 (s, 3H) . 2.29 (s, 3H), 3.74 (m, 1H) , 4.19 (m, 1H), 4.84 (d, 1H), 7.09 (m, 1H), 7.34 (m, 1H) , 7.85 5 (m, 1H), 9.02 (s, 1H); MS (ES): 343.2 (M'+l). 4-(4 -trans-hydroxycyclohexyl)amino-5,6-dimethyl -2- (3 -thienyl) -7#-pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz, CDC1?) 6 1.21-1.60 (m. BH) , 1.98 (s, 3H) . 2.23 {s, 3H) , 3.66 (m, i 1H), 4.22 (m, 1H), 7.27 (m, 1H) , 7.86 (m, 1H), 8.09 (m, 1H) , 11.23 (S, 1H); MS (ES) : 343.2 (M'+l) . 4 -(4-crans-hydroxycyclohexyl)amino-5,6-dimethyl-2-(4-fluorophenyl)-7tf-pyrrolo[2,3d]pyrimidine. JH NMR (200 MHz, CDC13) 6 1.26- 1.66 (m, 8H), 1.94 (s, 3H), 2.28 (s, 3H) , 3.73 (m, 1H), 4.33 (m, 1H), 4.92 (d, 1H) , 7.13 (m, 2H) , 8.41 (m, 2H) , 11.14 (S, 1H) ; MS (ES) : 355.2 (M'+l). 4 -(4 -crans-hydroxycyclohexyl)amino-5,6-dimethyl-2 -(3 -fluorophenyl)-7H-pyrrolo[2,3d]pyrimidine. ;H NMR (200 MHz, CDClj) 6 1.26-1.71 (m, 8H), 2.06 (s, 3H) , 2.30 (s, 3H), 3.72 (m, 1H), 4.30 (m, 1H), 4.90 (d, 1H) , 7.09 (m, 1H), 7.39 (m, 1H) , 8.05 (m, 1H) , 8.20 (m, 1H) , 10.04 (s. 1H) ; MS (ES) : 355.2 (M' + l) . 4 -(4 -crans-hydroxycyclohexyl)amino-5,6-dimethyl-2-(2-fluorophenyl)-7H-pyrrolo[2,3d]pyrimidine. ;H NMR (200 MHz, CDC13) 5 1.30-1.64 (m, 8H), 2.17 (s, 3H), 2.31 (s, 3H), 3.73 (m, 1H), 4.24 (m, 1H) , 4.82 (d, 1H) , 7.28 (m, 2H), 8.18 (m, 1H), 9.02 (m, 1H), 12.20 (s, 1H); MS (ES): 355.3 (M'+l). 4- (4- crans-hydroxycyclohexyl) amino-5, 6-dimechyl-2-isopropyl- 7H-pyrrolo [2,3d] pyrimidine ;H NMR (200 MHz. CDC13) 6 1.31 (d, J » 7.0 Hz, 6H) , 1.30-1.65 (m, 8H) , 2.27 (s, 3H) , 2.28 (s, 3H) , 3.01 (m, J = 7.0 Hz, 1H) , 3.71 (m, 1H) , 4.14 (m, 1H) , 4.78 (d, 1H); MS (ES): 303.2. dl-4 -(2-crans-hydroxycyclohexyl)amino-5,6-cime-hyi-~-isopropyl-7#-pyrrolo[2,3d]pyrimidine "K NMR (200 MHz, CDCl-:'- d 1.31-1.42 (br, 4H), 1.75-1.82 (br, 4H), 2.02 (s, 3H). 2.25 (S, 3H), 3.53 (m, 1H) , 4.02 (m, 1H) , 5.08 (d, 1H) , 7.41-7.48 (m, 3H), 8.30 (m, 2H) , 10.08 (s, 1H); MS (ES) : 337.2 (M*»l). 4 - (3 , 4 - trans-dihydroxycyclohexyl) amino-5, 6 -dimethyl - 2-phenyl -7H-pyrrolo [2,3d]pyrimidine. MS (ES) : 353.2 (M**!). 4- (3,4-cis-dihydroxylcyclohexyl) amino-5, 6-dimethyl-2-phenyl-7#-pyrrolo [2,3d] pyrimidine. MS (ES) : 353.2 (M%1). 4 -(2-acetylaminoethyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine. mp 196-199°C; :H NMR (200 MHz, CDCl,) 6_1.72 (s, 3H) , 1.97 (s, 3H), 2.31 (s, 3H), 3.59 (m, 2H) , 3.96 (m, 2H), 5.63 (br, 1H) , 7.44-7.47 (m. 3H) , 8.36-8.43 (dd. J « l Hz, 7 Hz, 2H), 10.76 (S, 1H); MS (ES) : 324.5 (M'+l) . dl-4- (2- crajis-hydroxycyclopentyl) amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine.: :H NMR (200 MHz, CDCl,) 6_1.62 (m, 2H) , 1.79 (br, 4H) , 1.92 (S, 3H) , 2.29 (s, 3H) , 4.11 (m, 1H), 4.23 (m, 1H), 5.28 (d, 1H) , 7.41-7.49 (m, 3H) , 8.22 (m, 2H) ,. 10.51 (s, 1H) ; MS (ES) : 323.2 (M' + D. '• For preparation of 2- crans-hydroxycyclopencylamine, see PCT 9417090. dl-4- (3- crans-hydroxycyclopentyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine.' :H NMR (200 MHz, CDCl,) 5_1.58-1.90 (br, 6 H, ) , 2.05 (s, 3H) , 2.29 (S. 3H) , 4.48-4.57 (m, 1H) , 4.91-5.01 (m, 2H) , 7.35-7.46 (m, 3H) , 8.42-8.47 (m, 2H) . 10.11 (s, 1H) ; MS (ES) : 323.2 (M' + l) - : For preparation of 3-traj2s-hydroxycyclopentylamine, see E?-A-322242. dl-4- (3-cis-nydroxycyclopencyl)amino-5,6-dimethyl-2-phenyl-7#-pyrrolo [2,3d]pyrimidine.: :H NMR (200 MHz, CDCl,) 6_1.82-2.28 (br. 6H) , 2.02 (s, 3H) , 2.30 (s, 3H) , 4.53-4.60 (m, 1H), 4.95-5.08 (m, 1H) , 5.85-5.93 (d, 1H) , 7.35-7.47 (m, 3H) , 8.42-8.46 (m, 2H) , 10.05 (s, 1H) ; MS (ES) : 323.2 (M'+l) . - For preparation of 3-cis-hydroxycyclopentylamine, see EP-A-322242. 4 - (3,4- crazzs-dihydroxycyclopentyl) amino-5,6-dimethyl-2 -phenyl -7tf-pyrrolo[2,3d]pyrimidine.1 :H NMR (200 MHz, CDC1,) 5_1.92- 1.99 (br, 2H) , 2.14 (s, 3H) , 2.20 (br, 2H) , 2.30 (s, 3H) , 2.41-2.52 (br, 2H), 4.35 (m, 2H), 4.98 (m. 2H), 7.38-7.47 (m, 3H) , 8.38-8.42 (m, 2H) , 9.53 (s, 1H) ; MS (ES) : 339.2 (M' + l). : For preparacion of 3,4-trans-dihydroxycyclopentylamine, see PCT 9417090. 4 -(3-amino-3-oxopropyl)amino-5,6-dimethyl-2-phenyl-7H- pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz, CDC1,) 6_2.02 (s, 3H) , 2.29 (s, 3H) , 2.71 (t, 2H) , 4.18 (m, 2H) , 5.75-5.95 (m, 3H) , 7.38-7.48 (m, 3H) , 8.37-8.41 (m, 2H) , 10.42 (s, 1H) ; MS (ES) : 310.1 (M'-t-l). 4- (3-N-cyclopropylmechylamino-3-oxopropyl) amino-5,6-dimethyl-2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHz, CD,OD) 5_0.51 (q, 2H), 0.40 (q, 2H), 1.79-1.95 (br, 1H), 2.36 (s, 3H) , 2.40 (s, 3H) , 2.72 (t, 2H) , 2.99 (d, 2H) , 4.04 (t, 2H) , 7.58-7.62 (m, 3H), 8.22-8.29 (m, 2H); MS (ES): 364.2 (M'+l). 4- (2-amino-2-oxoethyl) amino-5,6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine 'H NMR (200 MHz, CD?OD) 6 2.31 (s, 3H) , 2.38 (s, 3H) , 4.26 (s,-2H), 7.36 (m, 3H) , 8.33 (m, 2H) ; MS (ES) : 396.1 (M' + l) . 4- (2-N-methylaraino-2-oxocchyl) amino-5, 6-dimethyl-2-pher.yl-7/--pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz. CDCI:) 6_1.99 (s, 3H) , 2.17 .(s, 3H) , 2.82 (d, 3H) , 4.39 (d, 2H) , 5.76 (t, 1H) , 6.71 (br, 1H) , 7.41-7.48 (m, 3H) , 8.40 Cm, 2KJ , 10.66 (s. 1H) ; MS (SS) : 310.1 (M'+l) . 4- (3- cert- bucyloxy 1-3 -oxopropy l ) amino-5, 6-dimethyi-2-phenyl-7#-pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz, CDCI,) 6_1.45 (s, 9H) , 1.96 (S, 3H) , 2.29 (s, 3H) , 2.71 (t, 2H) , 4.01 (q, 2H) , 5.78 (t, 1H) , 7.41-7.48 (m, 3H) , 8.22-8.29 (m, 2H) ,- MS (ES) : 367.2 (M"+l) . 4 - ( 2 -hydroxyethyl ) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. ;K NMR (200 MHz, CDCI,) 6 1.92 (s, 3H) , 2.29 (S, 3H) , 3.81-3.98 (br, 4H) , 5.59 (t, 1H) , 7.39-7.48 (m, 3H) , 8.37 (m, 2H) , 10.72 (s, 1H) ; MS (ES) : 283.1 4 - ( 3 -hydroxypropyl ) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo[ 2, 3d] pyrimidine. :H NMR (200 MHz, CDC1:.) 6 1.84 (m, 2H) , 1.99 (s, 3H), 2.32 (s, 3H) , 3.62 (t, 2H) , 3.96 (m, 2H) , 3.35 (C, 1H) , 7.39-7.48 (m, 3H) , 8.36 (m, 2H) , 10.27 (s, 1H) ; MS (ES) : 297.2 (M'+l) . 4- (4-hydroxybutyl) amino-5, 6 -dimechyl -2 -phenyl-7H-pyrrolo [ 2, 3d] pyrimidine. ;H NMR (200 MHz, CDCI,) 6 1.71-1.82 (m, 4H) , 1.99 (S, 3H) . 2.31 (S, 3H) , 3.68-3.80 (m, 4H) , 5.20 (t, 1H) , 7.41-7.49 (m, 3H) , 8.41(m, 2H) , 10.37 (s, 1H) ; MS (ES) : 311.2 (M'f 1) . 4 - ( 4 - crans-acetylaminocyclohexyl ) amino-5 , 6 -dimethyl - 2 -phenyl -7H-pyrrolo [2 , 3d] pyrimidine . 4 - (4- crans-methylsulfonylaminocyclohexyl) amino-5, 6 -dimethyl -2 -phenyl - 7H-pyrrolo [2 , 3d] pyrimidine . 4- (2-acetylaminoethyl)amino-5,6-dimethyl-2-phenyl-7£-7- ;i-phenylethyl)pyrrolo[2,3d]pyrimidine. 4 - (4 - trans-hydoxycyclohexyl) amino- 5, 6 -dimethyl - 2 -phenyl - 7 H-1 -phenylethyl) pyrrolo [2,3 d] pyrimidine. 4- (3-pyridylmethyl)amino-5,6-dimethyl-2-phenyl-7H-7- (l -phenylethyl} pyrrolo [2, 3dJ pyrimidine. 4 - (2-methylpropyl)amino-5,6-dimethyl-2-phenyl-7H-7-(1-phenylethyl}pyrrolo[2,3d]pyrimidine. Exuqplc 2: To a stirred suspension of triphenylphosphine (0.047 g, 0.179 mmol) and benzoic acid (0.022 g, 0.179 mmol) in THF (1.0 mL) cooled to 0°C was added 4- (4-crans-hydroxycyclohexyl)amino- 5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine (0.05 g, 0.149 mmol) at 0°C. Diethyl azodicarboxylate (0.028 ml, 0.179 mmol) was then added dropwise over 10 minutes. The reaccion was then allowed to warm to room temperature. After reaction was complete by TLC the reaction mixture was quenched with agueous sodium bicarbonate (3.0 mL). The aqueous phase was separated and extracted with ether (2 X 5.0 mL). The organic extracts were combined, dried, and concentrated In vacuo to dryness. To the residue was added ether (2.0 mL) and hexane (5.0 mL) whereupon the bulk of the triphenylphosphine oxide was filtered of f. Concentration of the filtrate gave a viscous oii which was purified by column .chromatography (hexane :ethyl acetate»4:l) to give 5.0 mg (7.6%) of 4-(4- cis-benzoyloxycyclohexyl)amino-5,6-dimethyl-2-phenyl-7H- pyrrolol 2,3d] pyrimidine. MS (ES) : 441.3 (M'+i) . The reaction also produced 50.0 mg (84V) of 4- (3-cyclohexenyl)amino-5,6- dimethyl -2 -phenyl-7H-pyrrolo [2. 3d] pyrimidine. MS (ES) : 319.2 (M'+l). Exaunple 3: To a solution of 4- (4-cis-benzoyloxycyclohexyl)amino-5,6~ dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine (5.0 mg, 0.0114 mmol) in cthanol (1.0 mL) was added 10 drops of 2M sodium hydroxide. After l hr, the reaction mixture was extracted with ethyl acetate (3 x 5.0 mL) and the organic layer was dried, filtered and concentrated in vacuo to dryness. The residue was subjected to column chromatography (hexane:ethyl acetate-4:l) to give 3.6 mg (94%) of 4-{4-cis-hydroxycyclohexyl)amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine. MS (ES) : 337.2 (M"*D . The following compounds were obtained in a similar manner as that of Example 3: 4- (3-N,N-dimethyl-3-oxopropyl)amino-5,6-dirnethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. ;H NMR (200 MHz, CDCl,) 6 2.01 (s, 3H) , 2.31 (S, 3H) , 2.73 (t, 2H), 2.97 (s, 6H), 4.08 (m, 2H), 6.09 (t, 1H), 7.41-7.48 (m, 3H) , 8.43 (m, 2H), 10.46 {s, 1H) ; MS (ES): 338.2 (M'+l). 4 -(2-formylaminoethyl) amino-5 , 6-dimethyl-2-phenyl-7#- pyrr ol o [2,3 d] pyrimidine. 'H NMR (200 MHz, CDCl,) 6 2.26 (s, 3H) . 2.37 (s, 3H) , 3.59-3.78 (m, 2H) , 3.88-4.01 (m, 2H) , 5.48-5.60 (m, 1H). 7.38-7.57 (m, 3H) , 8.09 (s, 1H), 8.30-8.45 (m, 2H), 8.82 (s, 1H); MS (ES): 310.1 (M'+l). 4 -(3-acetylaminopropyl)amino-5, 6-dimethyl- 2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 338.2 (M*«-l) . Exanple 4: 4- (3-terc-butyloxy-3-oxopropyl)amino-5,6-dimethyl-2-phenyi-7H-pyrrolo[2,3d]pyrimidine (70.0 mg, 0.191 mmol) ) was dissolved in trifluoroacetic acid:dichloromethane (1:1, S.O mL) . The resulting solution was stirred ac room temperacure for l hr. and then refluxed for 2 hr. After cooling down to room temperatura, che mixture was concentrated in vacuo to dryness. The residue was subjected to preparative chin layer chromatography (EtOAc:hexane: AcOH=7:2.5:0.5) to give 40.0 mg (68%) of. 4- (3-hydroxy-3-oxopropyl)amino-5, 6-dimethyl-2-phenyl-7Hrpyrrolo[2,3d] pyrimidine. :H NMR (200 MHz, CD3OD) 6 2.32 (s, 3H) , 2.38 (s, 3H), 2.81 (t, 2H) , 4.01 (t, 2H) , 7.55 (m, 3H), 8.24 (m, 2H); MS (ES) : 311.1 (M*+l) . The following compound was obtained in a similar manner as that of Example 4: 4- (3-aminopropyl)amino-5,6-dimethyl-2-phenyl-7W-pyrrolo[2,3d]pyrimidine. MS (ES) : 296.1 (M*+l) , 279.1 (M*-NH3) . Example 5: 4 - (3-hydroxy-3-oxopropy l) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2,3d]pyrimidine (50.0 mg, 0.161 mmol) was dissolved in a mixture of N,N-dimethylformamide (0.50 mL) , dioxane (0.50 mL) and water(0.25 mL) . To this solution was added methylamine (0.02 mL, 40% wt in water, 0.242 mmol), triethylamine (0.085 mL) and N,N,N'N'-tetramethyl uronium tetrafluoroborate (61.2 mg, 0.203 mmol). After stirring at room cemperature for 10 min, the solution was concentrated and the residue was subjected to preparative thin layer chromatography (EtOAc) to give 35.0 mg (67%) of 4-(3-N-mechyl-3-oxopropyl) amino-5 , 6-dimethyl-2-phenyl-7#- pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, CDC10 6 1.92 (s, 3H) , 2.30 (s, 3H) , 2.65 (t, 2H) , 4.08 (t, 2H) , 5.90 (t, 1H), 6.12 (m, 1H) , 7.45 (m, 3H) , 8.41 (m, 2H) , 10.68 (s, 1H) ; MS (ES) : 311.1 (M'+D . The following compounds were obtained in a similar manner as thac of Example 5: 4-(2-cyclopropanecarbonylaminoethyl)amino-5,6-dimethyl-2-phenyl - 7#-pyrrolo[2,3d]pyrimidine. MS (ES) : 350.2 (M'+i) . 4-(2-isobutyrylaminoethyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. MS (ES) : 352.2 (M'+l) . 4-(3-propionylaminopropyl)amino-5,6-dimethyl-2-phenyl-7#- pyrroIo [2, 3d]pyrimidine. :H NMR (200 MHz, -CDC1?) 5 1.00-1.08 (t, 3H) , 1.71-2.03 (m, 4H), 2.08 (S, 3H), 2.37 (s, 3H), 3.26- 3.40 (m, 2H), 3.79-3.96 (m, 2H) , 5.53-5.62 (m, 1H),_6.17-6.33 (m, 1H) , 7.33-7.57 (m, 3H) , 8.31-8.39 (m, 2H), 9.69 (s, 1H) ; MS (ES): 352.2 (M'+l). 4- (2-methylsulfonylaminoethyl)amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2,3d] pyrimidine. 'H NMR (200 MHz, CDC13) 6 2.18 (s, 3H), 2.27 (s, 3H), 2.92 (s, 3H) , 3.39-3.53 (m, 2H) , 3.71-3.88 (m, 2H), 5.31-5.39 (m, 1H), 6.17-6.33 (m, 1H) , 7.36-7.43 (m, 3H), 8.20-8.25 (m, 2H), 9.52 (s, 1H); MS (ES): 360.2 (M*+l). Exaapl* 6: A tnixture of 4-chloro-5, 6-dimethyl-2Tphenyl-7H-pyrrolo [2,3d] pyrimidine (0.70 g, 2.72 mmol) and l,2-diaminoethane (10.0 mL, 150 mmol) was refluxed under inert atmosphere for 6 hr. The excess amine was removed in vacuo, the residue was washed sequentially with ether and hexane to give 0.75 g (98V) of 4-(2-aminoethyl)amino-5,6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. MS (ES) ; 282.2 (M* •*•!), 265.1 (M"-NH3) . Exaatplc 7: To a solucion of 4- (2-aminoethyl)amino-5,6-dimechyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine (70.0 mg, 0.249 mmol) and criethylamine (50.4 mg, 0.498 mmol) in dichloromethane (2.0 mL) was added propionyl chloride (25.6 mg, 0.024 mL, C. "74 mmol) at 0°C. After l hr, che mixture was concentrarea ir. vacuo and the residue was subjected to preparative chin layer chromatography (EtOAc) to give 22.0 mg (26%) of 4-(2-propionylaminoethyl)amino-5,6-dimethyl-2-phenyl-7H- pyrrolo[2,3d]pyrimidine. MS (ES) : 338.2 {M*•*•!). The following compounds were obtained in a similar manner as chat of Example 7: 4-(2-N1-methylureaethyl)amino-5,6-dimethyl-2-phenyl-7tf- pyrrolo [2,3d]pyrimidine. :H NMR (200 MHz, CDCl,) 6 2.13 (s, 3H), 2.32 (s, 3H), 3.53 (d, 3H) , 3.55 (m, 2H) , 3.88 (m, 2H) , 4.29 (m. 1H), 5.68 (C, 1H), 5.84 (m, 1H) , 7.42 (m, 3H), 8.36 (dd, 2H), 9.52 (s, 1H); MS (ES): 339.3 (M*+l). 4-(2-N1-echylureaechyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine. MS (ES) : 353.2 (M' + l). Exajnple 8: To a solution of l-(3-dimcchylaminopropyl)-3-echylcarbodi-imide hydrochloride (41.1 mg, 0.215 mmol}, dimechylamino-pyridine (2.4 mg, 0.020 mmol) and pyruvic acid (18.9 mg, 0.015 mL, 0.215 mmol) in dichloromethane (2.0 mL) was added 4- (2-aminoechyl)amino-5, 6-dimechyl-2-phenyl-7#-pyrrolo [2, 3d] pyrimidine (55.0 mg, 0.196 mmol). The mixcure was stirred at room temperatura for 4 hr. Usual workup and column chromatography (EtOAc) then gave 10.0 mg (15%) of 4-(2'-pyruvylamidoethyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine.. MS (ES): 352.2 (M"*l). Exaapla 9: ' To a solucion of 4 - (2-aminoethyl)amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine (60.0 mg, 0.213 mmol) in dichloromethane (2.0 mL) was added N-trimethylsilyl isocyanate (43.3 mg, 0.051 mL, 0.320 mmol). The mixture was scirred ac room temperatura for 3 hr fcllowed by add-tior. c f agueous sodium bicarbonace. Afcer filtration through small amount of silica gel, the filtrate was concentrated in vacuc to dryness co give 9.8 mg (14%) of 4- (2-ureaethyl) amino-5, 6-dime thyl -2 -phenyl -7#-pyrrolo [2, 3d] pyrimidine. MS (ES> : 325.2 The following compounds were obtained in a similar manner as thac of Example 9: dI-4- (2-acetylaminopropyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolol 2, 3d] pyrimidine. :H NMR (200 MHz, CDC1,) 6 1.28-1.32 (d, J*8 Hz, 3 H), 1.66 (s, 3H) , 1.96 (s, 3H) , 2.30 (s, 3H) 3.76-3.83 (m, 2H) , 4.10-4.30 (m, 1H) , 5.60-5.66 (C, J«6 Hz , 1H) , 7. 40-7. 51 (m, 3H) , 8.36-8.43 (m, 2H) , 10.83 (s, 1H) ; MS (ES) : 338.2 (M*+l) . (R) -4- (2-acecylaminopropyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHz, CDC13) 6 1.31 (d, 3H) , 1-66 (s, 3H) 1.99 (s, 3H) , 2.31 (s, 3H) , 3.78-3.83 (m, 2H) , 4.17-4.22 (m, 1H) , 5.67 (t, 1H) , 7.38-7.5 (m, 3H) , 8.39 (m, 2H) , 10.81 (s, 1H) ; MS (ES) : 338.2 (M"+l) . (R) -4- (l-methyl-2-acecylaminoethyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. :H NMR (200 MHz. CDCl,} 6 1.41 (d, 3H) , 1.68 (s, 3H) , 2.21 (s, 3H) , 2.34 (s, 3H) , 3.46-3.52 (br, m, 2H) , 4.73 (m, 1H) , 5.22 (d, 1H) , 7.41-7.46 (m, 3H) , 8.36-8.40 (m, 2H) , 8.93 (s, 1H) ; MS (ES) : 338.2 (M'+l). (S) -4 - (2-acetylaminopropyl) amino-5 , 6 -dimethyl -2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine. ;H NMR (200 MHz, CDC13) 6 1.31 (d, 3H) , 1.66 (s, 3H) 2.26 (s, 3H) , 2.35 (s, 3H) , 3.78-3.83 (m, 2H) , 4.17-4.22 (m, 1H) , 5.67 (t, 1H) , 7.38-7.5 (m, 3H) , 8.39 (m, 2H) , 8.67(s, 1H) ; MS (ES) : 338.2 (M'+l). (S) -4 - (l-methyl-2-acetylaminoethyl) amino-5 , 6 - dimethyl -2-3henyl-7H-pyrrolo [2, 3d] pyrimidine. 'H NMR (200 MHz, CDC1J 5 1.41 (d, 3H), 1.68 (s, 3H), 2.05 (s, 3H), 2.32 (s. 3K) , 2.46-3.52 (m, 2H) , 4.73 (m, 1H) , 5.22 (d, 1H) , 7.41-7.46 (m, 3K! , 8.36-8.40 (m, 2K} , 10.13 (s, 1H); MS (ES) : 338.2 (M'*l). Exajnple 10: Reaccion of 4-chloro-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine with che mixture of dI-l-amino-2-(l,1-dimechyl e t hoxy) carbonylamino -propane and dI-2-arr.ino-i- (l, l-dimechyl ethoxy) carbonylamino-propane was run in a similar manner as that of Example l. The reaccion gave a mixture of dI-4-d- methyl-2- (l,1-dimethylcthoxy)carbonylamino)ethylamino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2, 3d]pyrimidine and dl-4-(2- methyl-2-(l,l-dimethylethoxy)carbonylamino)ethylamino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2, 3d] pyrimidine which were separated by column chromatography (EtOAc:hexanes=sl :3) . The first fraction was dl-4-(l-methyl-2-(l,1-dimethylethoxy) carbonylaminoethyl)amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine: ;H NMR (200 MHz, CDC1,) 6 1.29 - 1.38 (m, 12 H). 1.95 (s, 3H) , 2.31 (s, 3H) 3.34-3.43 (m, 2H) , 4.62-4.70 (m, 1H), 5.36-5.40 (d, J-8 Hz, 1H), 5.53 (br, 1H) , 7.37-7.49(m, 3H), 8.37-8.44(m, 2H), 10.75 (s, 1H). MS 396.3 (M'-t-l); The second fraction was dl -4- (2- (l, 1- dimethylethoxy)carbonylaminopropyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d]pyrimidine: :H NMR (200 MHz, CDC13) 6 1.26-1.40 (m, 12 H), 2.00 (s, 3H) , 2.31 (s, 3H) 3.60-3.90 (m, 2H), 3.95-4.10 (m, 1H), 5.41-5.44 (d, J-6.0 Hz, 1H), 5.65(br, 1H) , 7.40-7.46{m, 3H) , 8.37-8.44(m, 2H) , 10.89 (s, 1H) ; MS (ES) : 396.2 (M' + l) . The following compounds were obtained in a similar manner as that of Example 10: (S,S)-4-(2-acetylaminocyclohexyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, CDC13) 6_1.43 (m, J H), 1.60 (s, 3 H), 1.83 (m, 2 H), 2.18 (s, 3 H), 2.30 (m, l H), 2.32 (s, 3 H), 3.73 (br, 1H), 4.25 (br, 1H), 5.29 (d, .H), 7.43-7.48 (m, 3H), 8.35-8-40 (m, 2H), 9.05 (s, l H). 4- (2-methyl-2-acetylarninopropyl) amino-5, 6-dirnechyl-2-phenyI-7H-pyrrolo [2,3d] pyrimidine. :H NMR (200 MHz, CDC1:.) 5_l.5i (s, 6H) , 1.56 (s, 3H) , 2.07 (s, 3H), 2.36 (s, 3H). 3.76 (d, 2K) , 5.78 (t, 1H), 7.41-7.48 (m, 3H), 7.93 (s, 1H), 8.39 (m, 2H), 10.07 (s, 1H); MS (ES): 352.3 (M'+l). Exaunple 11: dl-4- (l-rnethyl-2- (l, 1-dimethylechoxy) carbonyl aminoechyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine (60.6 mg, 0.153 mmol) was treated with trifluoroacetic acid (0.5 mL) in dichloromethane (2.0 mL) for 14 hr. The organic solvent was removed in vacuo to dryness. The residue was dissolved in N,N-dimechylformamide (2.0 mL) and triethylamine (2.0 mL) . To the solucion at 0°C was added acetic anhydride (17.2 mg, 0.016, 0.169 mmol). The resulted mixcure was stirred at room temperature for 48 hr and then concentrated in vacuo to dryness. The residue was subjected to preparative thin layer chromatography (EtOAc) to give 27.0 mg (52%) of dJ-4-(l-methyl-2-acetylaminoethyl)amino-5,6-dimethyl-2- phenyl-7H-pyrrolo[2,3d]pyrimidine. :H NMR (200 MHz, CDC10 5 1.38-1.42 (d, J-8 H2, 3 H), 1.69 (s, 3H) , 2.01 (S, 3H), 2.32 (s, 3H) 3.38-3.60 (m, 2H), 4.65-4.80 (m, 1H), 5.23-5.26 (d, J=6 HZ, 1H), 7.40-7.51(m, 3H) , 8.37-8.43(m, 2H) , 10.44 (s, 1H) ; MS (ES) : 338.2 (M' + l) . Example 12: (R,R)-4- (2-aminocyclohexyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine, prepared in a similar manner as that of Example l f rom 4-chloro-5,6-dimethyl-2-phenyl-7H- pyrrolo[2,3d]pyrimidine (0.15 g, 0.583 mmol) and (IR, 2R)- (-)-l, 2-diaminocyclohexane (0.63 g, 5.517 mmol), was treated with triethylamine (0.726 g, 7.175 mmol) and acetic anhydride (0.325 g, 3.18 mmol) in N,N-dimethylformamide (10.0 mL) at room temperature for 2 hr. After removal of solvent in vacuo, ethyl acetate (10.0 mL) and water (10.0 mL) were added to the residue. The mixture was separated and the aqueous layer was oxohexyl)amino-5,6-dimethyl-2-phenyl-7tf-pyrrclo[2. 3c] pyrimidinc. MS (SS) : 353.2 (M'+l) . Exanple 15: A solution of 4-(2-aminoechyl)amino-5,6-dimechyl-2-phenyi-7H- pyrrolo[2,3d]pyrimidine (70.0 mg, 0.249 mmol) and succinic anhydride (27.0 mg, 0.274 mmol) in dichloromethane (4.0 mL) with l drop of N,N-dimethylformamide was scirred at room temperatura for 4 hr. The reaction mixture was extracced wich 20* sodium hydroxide (3 x 5.0 mL). The aqueous solution was acidified with 3 M hydrochloride to pH = 7.0. The whole mixture' was extracted with ethyl acetate (3 x 10 mL) . The combined organic solution was dried (MgSO«) and filtered. The filtrate was concentrated in vacuo to dryness to give 15.0 mg (16%) of 4-(7-hydroxy-3-aza-4,7-dioxoheptyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyriraidine. MS (ES) : 382.2 (M'+l) . Exaunpl» 16: To 10 mL of dimethyl f ormamide (DMF) at room temperature were added 700 mg of 4-cis-3-hydroxycyclopentyl) amino-2-phenyi- 5,6-dimethyl-7H-pyrrolo[2.3d]pyrimidine followed by 455 mg of N-Boc glycine, 20 mg of N,N-dimethylaminopyridine (DMAP), 293 mg of hydroxybenzotriazole (HOBT) and 622 mg of l-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (EDC1). The reaction mixture was left stirring overnight. DMF was then removed under reduced pressure and the reaction mixture was partitioned between 20mL of ethyl acetate and 50mL of water. The aqueous portion was extracted further with 2x2OmL of ethyl acetate and the combined organic portions were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification on silica gel, eluting with ethyl acetate/hexane gave 410 mg of the desired product : 4- (cis-3-(N-1-butoxycarbonyl- 2-aminoacetoxy) cyclopentyl) amino-2-phenyl-5,6,-dimechyl-7#-pyrrolo[2,3d] pyrimidine, MS (ES) (M't-1) «480 . 2 . The ester was then treated with 5 raL of 20% trifluoroacecic acid in dichloromethar.s az room temperature, left over night and chen concer.-racec. Trituration wich ethyl acetate gave 300 mg of an off whice solid; 4- {cis-3- (2-aminoacetoxy)cyclopentyl) amino-5, 6-dimerhy l-2-phenyl-7ff-pyrrolo [2,3d] pyrimidine trifluoroacetic acid salt, MS (ES) (M*+l) «380.1. One skilled in the art will appreciate that the following compounds can bc synthesized by the methods disclosed above: 4-{cis-3-hydroxycyclopentyl}amino-5 , 6-dimethyl-2-phenyl-7H-pyrrolo[2,3d] pyriraidine MS (ES) (M"+l) 323.1. 4-(cis-3-(2-aminoacetoxy)cyclopentyl)amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3d] pyrimidinetrifluoroacetic acid salt MS (ES) (M*+l)« 380.1. 4- (3-acetamido)piperidinyl-5, 6-dimethyl-2-phenyl-7H-pyrrolo[2, 3d]pyrimidine MS (ES) (M**l)« 364.2. 4- (2-N' -methylureapropyDamino-5, 6 -dimethyl-2-phenyl- 7H-pyrrolo[2,3d] pyrimidine, MS (ES) (M"+i)«353.4. 4 - (2-acetamidobutyl)amino-5,6-dimethyl- 2-phenyl-7H-pyrrolo[2,3d]pyrimidine, MS (ES) (M'+l)« 352.4. 4 -(2-N'-methylureabutylj amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine MS (ES) (M'-t-l). 367.5 4 -(2-aminocyclopropylacetamidoethyl)amino-2-phenyl-7H-pyrrolo[2,3d] pyrimidine MS (ES) (M'+l)= 309.1. 4 - (crans-4-hydroxycyclohexyl)amino-2-(3-chlorophenyl)-7H- pyrrolo[2,3d] pyrimidine MS (ES) (M'-t-l: «342 . 8 . 4- (craj3S-4-hydroxycyclohexyl)amino-2- (3-fluorcphenyl) -7H-pyrrolo [2,3d] pyrimidine MS (ES) (M"-!)»327.2. 4 - (crans-4-hydroxycyclohexyl)anino-2 - (4-pyridyl) - 7H-pyrrolol2,3d]pyrimidire MS (ES) (M"+l)-310.2. Exanple 17 (Figure Removed) The pyrrolc nitrogen of (7) (Scheme IX) was procecced wich di-c-bucyldicarbonace under basic condiţiona to yield the corresponding carbamate (22). Radical bromination of (22) proceeded regioselectively to yield bromide (23). In general, compound (23) served as a key electrophilic intermediate for various nucleophilic coupling partners. Displacement of the alJcyl bromide wich sodium phenolate crihydrace yielded compound (24) . Subsequent displacement of the aryl chloride and removal of the c-bucyl carbamaze protecting group occurred in one step yieldinc deşire-compound (25) . Datailed Synth«sis of Compound (22)-(25) in Aeeordance with Scheme IX (Figure Removed) Di-c-butyl dicarbonate (5.37 g, 24.6 mmol) and dimethyl aminopyridine (1.13 g, 9.2 mmol) were added to a solution containing (7) (1.50 g, 6.15 mmol) and pyridine (30 mL) . After" 20 h the reaction was concentrated and the residue was partitioned between CH:C1: and water. The CH:C1: layer was separated, dried over MgSO,, filtered and concentrated to yield a black solid. Flash chromatography (SiO2; 1/9 EtOAc/Hexanes, Rf 0.40) yielded 1.70 g (80%) of a white solid (22). LH NMR (200 MHz, CDC13) 5_8.50 (m, 2H, Ar-H) , 7.45 (m, 3H, Ar-H), 6.39 (s, 1H, pyrrole-H) , 2.66 (s, 3H,pyrrole-CHj) , 1.76 (s, 9H, (Figure Removed) N-Broraosuccinimide (508 mg, 2.86 mmol) and AIBN (112 mg, C.=5 mniol) were added co a solution containing (22) (935 mg, 2.71 mmol) and CC14 (50 mL) . The solucion was heaced co reflux. After 2 h che reaction was cooled co room temperacure and i concencraced in vacuo co yicld a whice solid. Flash chromatography (Si02; 1/1 CH:Cl:/Hexanes, Rf 0.30) yielded 960 mg (84%)of a whice solid (23). 1H NMR (200 MHz, CDC13) 5^8.52 (m, 2H, Ar-H), 7.48 (m, 3H, Ar-H), 6.76 (s, 1H, pyrrole-H), 4.93 (s, 2H,pyrrole-C#,Br) , 1.79 (s, 9H, carbamace-CH.-) ; MS, M + l - 423.9; Mpt 155-157°C. (Figure Removed) Sodium phenoxide trihydrate (173 mg, 1.02 mmol) was added in one portion co a solucion of bromide (23) (410 mg, 0.97 mmol) dissolved in CH,C1; (5 mL) and DMF (10 mL) . AfCer 2 h che reaccion solucion was parcicioned becween CH:C1: and water. The wacer layer was excracced wich CH:C1;. The combined CH:C1: layers were washed wich wacer, dried over MgS04, filcered and concencraced co yield a yellow solid. Flash chromacography (SiO2; 1/6 EtOAc/Hexanes, Rf 0.30) yielded 210 mg (50V) of a whice solid (24). XH NMR (200 MHz, CDC13) 6_8.53 (m, 2H, Ar- H) , 7.48 (m, 3H, Ar-H), 7.34 (m, 2H, Ar-H), 7.03 (m, 3H, Ar- H), 6.83 (s, 1H, pyrrole-H), 5.45 (s, 2H, ArCH:0) , 1.76 (s, 9H, carbamace-Cff.;) ; MS, M" * 436.2. (Figure Removed) A solution containing (24) (85 mg, 0.20 mmol) , N-acetylechylcnediamine (201 mg, 1.95 mmol) and DMSO (3 mL) was heated to 100°C. After l h the temperature was raised to 130*0. After 3 h the reaction was cooled to room temperature and partitioned between EtOAc and water. The water layer was extracted with EtOAc (2x). The combined EtOAc layers are washed with water, dried over MgSO., filtered and concentrated. Flash chromatography (SiO2; 1/10 EtOH/ CHCl,, Rf 0.25) yielded 73 mg (93%)of a white foamy solid (25). 1H NMR (200 MHz, DMSO-d6) 6 11.81 (br s, 1H, N-H), 8.39 (m, 2H, Ar-H), 8.03 (br t, 1H, N-H), 7.57 (br t, 1H, N-H), 7.20 -7.50 (m, 5H, Ar-H), 6.89 - 7.09 (m, 3H. Ar-H), 6.59 (s, 1H, pyrrole-H) , 5.12 (s, 2H, ArCH,0) , 3.61 (m, 2H, NCH-) , 3.36 (m, 2H, NCH..) , 1.79 (s, 3H.COCH.J; MS, M+ l 402.6 The following cornpounds were obtained in a manner similar to that of Example 17: 4 - (2-acetylaminoethyl)amino-6-phenoxymethyl-2-phenyl-7H-pyrrolo(2, 3d]pyrimidine. mp 196-197°C; MS (ES) : 401.6 (M' + l) . 4 - (2-acetylaminoethyl)amino-6-(4 - fluorophenoxy)methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. MS(ES): 420.1 (M'+l). 4 - ( 2 -acetylaminoethyl) amino-6- (4 -chlorophencxy i mec r.yl - ~ -phenyl-7H-pyrrolo[2,3d]pyrimidine. MS(ES): 435.1 (M'flî . 4- (2-acecylaminoethyl) amino-6- (4-tnechoxyphencxy: methyi-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. MS(ES): 432.1 (M'-!). 4- (2-acetylaminoethyl) amino-6- (N-pyridin-2-one) merhyl -2-phenyl-7H-pyrrolo[2,3d]pyrimidine. MS(ES): 403.1 (M'-cl) . 4 - (2 - acetylaminoethyl} amino- 6 - (N-phenylamino) methyl - 2 -phenyi -7#-pyrrolo[2,3]pyrimidine. MS(ES): 400.9 (M'+lî. 4- (2-acetylaminoethyl) amino-6- (N-methyl-N-phenyiamino)methyl-2-phenyl-7H-pyrrolo[2,3d]pyrimidine. MS(ES): 414.3 (M'*iî . 4- (2-N1 -methylureaethyl) amino-6-phenoxyrnethyl-2-phenyl- 7H-pyrrolo[2,3d]pyrimidine. MS (ES): 416.9 (M'+l). Exanple 18: Synthesis of adenosine Aa Antagoniste. Compound 1319 and Compound 1320 (Table 13 below) can be synthesized by the general procedures herein. (Figure Removed) Compound 1319 (81%) :H-NMR (d,-DMSO) d 1.37 (m, 4H) , 1.93 (m, 2H) , 2.01 (m, 2H) , 4.11 (brs, 1H) , 4.61 (d, 1H, J = 4.4 Hz), 6.59 (m, 1H), 7.09 (m, 1H), 7.21 (m, 2H), 7.49 (dd, 1H. J = 8Hz, 14Hz), 8.03 (m, 1H) , 8.18 (d, 1H. J = 8 Hz) , 11.55 (brs, 1H) . MS (ES) : 327.0 (M'-t-l) . Compound 1320 (31%) MS (ES) : 342.1 (M' + ll . Exaaple 19: Synthesis of adenoaine A! Antagonist. Compound 1321 (Table 13 below) can be synthesized b y the general procedures given below. (Figure Removed) Compound 28 (10.93g, 50.76 mmol) was dissolved in DMF (67 mL). 4-Amidinopyridine hydrochloride (S.Og, 50.76 mmol) and DBU (15.4 g, 101.5 iranol) were added sequentially and the reaction was heaced co 85°C. After 22 hours, the reaction was cooled to room tetnperature and the DMF was removed in vacuo. The dark oii was diluted with 2M HCI (80 mL) . The reaction was allowed to stand. After 2 hours, the solution was cooled to 10°C and filtered. The solid was washed with cold water and dried to yield 7.40g of a yellow solid, Compound 29 (69%). -H-NMR (200MHZ, d^-DMSO) d 6.58 (s, 1H) . 7.27 (s, 1H) , 8.53 (d, 2H, J - 5.6), 9.00 (d, 2H, J * 5.2HZ), 12.35 (brs, 1H). MS (ES): 212.8 (M*+l). Compound 29 (7.4 mmol. 29.8 mmol) was diluted with POCI, and heated to 105°C. After 18 hours, the reaction is cooled to room temperature and the POC1; is removed in vacuo. The thick dark oii is diluted with MeOH (75mL) followed by ether (120mL). The amorphous red solid is filtered and washed with ether to yield 3.82 g of a red solid. The crude solid is approximately 80% pure and used without further purification in the next reaction. MS (ES) : 230.7 (M'-t-l) . Compound 1321 -H-NMR (15%) (200MH, dr-DMSO) d 1.38 (n-., 4H: . 1.92 (brs, 2H), 2.02 (brs, 2H), 3.44 (brs, 1H), 4.14 (brs. 1H), 4.56 (d, 1H, J • 4 Hz), 6.63 (m, 1K), 7.15 (m, 1H). 7.32 (d, 1K, J * 6.2 Hz), 8.20 (d, 2H, J = 4.4 Hz), 8.c5 (d, 2H, J = 4.4HZ), 11.67 (brs, 1H) . MS (ES) : 310.2 (MVlî. Compound 1501 (Table 15 below) 'H-NMR (70%) (200MHz, CD,OD* c 1.84 (S, 3H), 3.52 (t, 2H, J - 6.0 Hz), 3.83, t, 2E, J - 6.0 Hz), 6.51 (d, 1H, J - 3.4HZ), 7.06 (d, 1H, J « 3.8 Hz), 7.42 (m, 3H) , 8.36 (m, 2H) . MS (ES) : 296.0 (M' + l) . Compound 1502 (Table 15 below) MS (ES): 345.0 (M'+l). Compound 1500 (Table 15 below) ;H-NMR (200MHZ, CDCl.,) d 1.40 - 1.80 (m, «N. 1.85 - 2.10 (m. 2HJ , 2.18 (s, 3H) , 2.33 (s, 3H), 2.50 (d, 3H) , 3.90 - 4.10 (m, 2H), 4.76 (m, 1H), 5.50 (d, 1H) , 6.03 (m, 1H) , 7.40 (m, 3H) , 8.37 (m, 2H) , 9.15 (brs, 1H) . MS (ES) : 393.3 fM'+l) . Exaaple 20: Syntheais of adenoaine At Antagoniet. Compound 1504 (Table 15 below) can be synthesized by the general procedures given below. (Figure Removed) Compound 31 (200 mg, 0.47 mmol) was dissolved in DCM (4 mL) . Triethylâmine (51 mg, O.Smmol) and chiomorpholine (52 mg, O.Smmol) were added sequencially. The solution was mixed for several minuces and allowed to stand for 72 hours. The reaction was diluced with DCM and H:0 and che layers were separated. The agueous layer was excracted with DCM. The combined DCM layers were dried over MgSO4, filtered and concencrated. Ethyi echer was added co the crude sampie ane the resulting solid was filcered to yieid lOOmg cf a whire solid, 32(62%). :HNMR (200MHZ, CDC1,) c 1.75 (s, 9H) , 2.6c (brs, 2H), 2.79 (brs, 2HJ, 3.86 (s, 2H), 7.46 im. 3K) , 6.50 (m, 2H). Compound 32 was combined with DMSO (3mL) and trans-4-aminocyclohexanol (144mg, 1.25 mmol) ane heatec to 130°C for 4 hours. The reaction was cooled co room temperatura, and diluted wich EtOAc and H:0. The iayers were separated and the aqueous layer was extracted with EtOAc (2x) . The combined organic Iayers were washed with H:0 and brine, dried over MgS04, filtered and concentrated. Chromacography (silica, 8:1 CHCl3/StOH) yields 32 mg of a tan oii. Sthyl ether was added and the resulting solid was filtered to yield 5 mg of a white solid (9%).OSIC-148265: :H-NMR (200MH2, CD?OD5 : d 1.44 (brm, 4H) , 2.03 (brtn, 2H) , 2.21 (brm, 2H) . 2.70 (brm, 8H) , 3.63 (m, 4H) , 3.92 (m, 1H), 4.26 (brs, 1H) , 6.42 (s, 1HJ , 7.42 (m, 3H) , 8.33 (m, 2H) . Sxaapl* 21 •' Syntheais of adenosine Aa Antagonist. Compound 1503 (Table 15 below) can be synthesized by the general procedures given below. (Figure Removed) The bromide, compound 31 (220 mg,' 0.47 mmol) was dissolved in 1:1 DMF:Dichloromethane (5 mL) . To this was added K?CO? (71 mg, 0.52 mmol) and morpholine (0.047 mL, 0.47 mmol). The mixture was allowed to ştir at room temperatura ovemight. Solvents were removed in vacuo and the residue was partitioned between H;0 and dichloromechane. The organic layerwas dried wich MgSO«, filtered, and concencraced ce give ar. off whice solid which upon cricuracion wich ether/hexar.ss gave 175tng of a whice solid, 33 (84%). :H-NMR (200MKz, COCI.) : ( 1.9 OH, s), 2.54 (4H, s), 3. S5 (4H. s), 3.S5 (1H. s), 6-59 (1H, S), 7.45 (3H, m),8.S (2H, m). Compound 33 (50 mg, 0.11 mmol) and rrans-4-aminocyciohexanol (105 mg, 0.91 mmol) were Caken up in DMSO (2mL) . The resulcant solucion was sparged wich N: and chen heaced co 100'C in an oii bach and scirred overnighc. The crude reaccion mixcure was poured inco wacer and excracced cwice wich echyl acecace (50mL). The combined organic layers were washed wich H;0. Afcer drying wich MgSO, and filcering, che organic layer was concencraced in vacuo co give an orange solid. Chromacography (silica, 10% CH,OH in CH:C1:) yielded I5mg (33%). :H-NMR ( 200 MHz, CDCl,) : ( 1.24 - 1.62 (4H. m), 1.85 (2H, m), 2.10 (2H, m), 2.26 (4H, m), 3.53 (4H, m), 4.22 (1H, m), 4.73 (1H, m), 5.85 (1H, d), 6.15 (1H, s), 7.25 (3H, m), 8.42 (2H, M), 10.0 (1H, s). MS (ES): 408 (M* + 1). Compounds 1500, 1501, and 1502 can be synChesized using similar preparacion sceps of Example 20 by creacing compound 32 wich an appropriacely subscicuced amine. Yeaat 3-Galactosidase reporter gene aasays for human adenosine A! and A2, receptor: Yeast strains (S. cerevisiaei were transformed with human adenosine A: (A:R; CADUS strair. CY12660) or human A2, (A2a; CADUS străin CY8362) and the addition of a lacZ(3-Galactosidase) reporter gene to urilize as a funcţional readout. A complete description of the transformations is listed below (see Yeast Strains). NECA (5'-N-ethylcarboxamidoadenosine), a potent adenosine receptor agonist with similar affinity for A: and A2a receptors, was used as a ligand for all assays. Test compounds were examined at 8 concentrations (0.1 - 10,000 nM) for ability to inhibit NECA-induced 3-Galactosidase activity by CY12660 or CY8362. Preparation of Yeast Stock Cultures: Each of the respective yeast strains, CY12660 and CY8362, were streaked onto an LT agar plate and incubated at 30°C until colonies were observed. Yeast f rom these colonies were added to LT liquid (pH 6.8) and grown overnight at 30°C. Each yeast străin was then diluted to an OD6()0 » 1.0-2.0 (approximately 1-2 X IO1 cells/ml), as determined spectrophotometrically (Molecular Devices VMAX) . For each 6 ml of yeast liquid culture, 4 ml of 40V glycerol (1:1.5 voi:voi) was added ("yeast/glycerol stock") . From this yeast/glycerol stock, ten l ml aliquots were prepared and stored at -80°C until required for assay. Yeast Ai R and A:aR Assay: One vial each of CY8362 and CY12660 yeast/glycerol stock was thawed and used to inoculate Supplemented LT liquid media, pH 6.8 (92 ml LT liquid, to which is added: 5 ml of 40% glucose, 0.45 ml of IM KOH and 2.5 ml of Pipes, pH 6.8). Liquid cultures were grown 16-18 hr (overnight) at 30"C. Aliquots f rom overnight cultures were chen diluced in LT media, containing 4U/ml adenosine ieaminase (Type VI or VII from calf intestinal mucosa, Sigma), to obtain ODţot - 0.15 (1.5 X 10£ cells/ml} for CY8362 (A2aR) and ODfoo - 0.50 (5X10* cells/ml) for CY12660 (AjR) . kssays were conducted with a final volume of 100 ui in 96- well microtiter plates, such that a final concern: r a cier. of 2% DMSO was achieved in all wells. For primary screer.inc. 1-2 concentrations of test compounds were utilized (10 uM. lyM î . For compound profiling, 8 concentrations were tested (10000, 1000, 500, 100, 50, 10, l and 0.1 nM) . To each microtiter place, 10 ui of 20* DMSO was added to "Control" and "Total" wells while 10 ui of Test Compound (in 20% DMSO) was added to "Unknown" wells. Subseguently, 10 ui of NECA (5 uM for A;R, l uM for A2aR) were added to "Total" and "Unknown" wells; 10 ui of PBS was added to the "Control" wells. In the final addition, 80 ui of yeast străin, CY8362 or CY126SO, were added to all wells. All plates were then agitated briefly (LabLine orbital shaker 2-3 min) and allowed to incubate for 4 hrs. at 30CC in a dry oven. 3-Galactosidase activity can be quantitated using either colorimetric (e.g., ONPG, CPRG), luminescent (e.g., Galacton-Star) or fluorometric substrates (e.g., FDG, Resorufin) substrates. Currently, fluorescence detection is preferred l on the basis of superior signal moise ratio, relative freedom f rom interference and low cost. Fluorescein digalactopyranoside (FDG, Molecular Probes or Marker Gene Technologies) , a fluorescent (î-Galactosidase substrate, was added to all wells at 20 ul/well (final concentration » 80 uM) . Plates were shaken for 5-6 sec (LabLine orbital shaker) and then incubated at 37°C for 90 min (95% O:/5% C0: incubator). At the end of the 90 min incubation period, 3-Galactosidase activity was stopped using 20 ul/well of IM Na;C03 and all plates shaken for 5-6 sec. Plates were then agitated for 6 sec and relative fluorescence intensity determined using a fluorometer (Tecan Spectrafluor; excitation 485 nm, emission 535 nm). Calculations: Relative fluorescence values for "Control" wells were interpreted as background and subtracted from "Total" and "Unknown" values. Compound profiles were analyzed via lagarithmic transformation (x-axis: compound concentration) followed by one site competition curve fitting to calculate IC*/, values (GraphPad Prism) . Yeast strains: Saccharomyces cerevisiae scrains CY12S60 [farl*1442 tbcl-l fusl-HIS3 câni ste!4 : :trpl: :LYS2 ste3*ll5£ gpal (41) -Gai3 Iys2 ura3 Ieu2 trpl: his3; LEU2 FGKp- MfalLeader-hAlR-PH05term 2mu-orig REP3 Ampr] and CY8362 [gpalp-rGasElOK farl*1442 tbtl-l fusl-HIS3 câni stel4::trpl: LYS2 Ste3*1156 Iys2 ura3 Ieu2 trpl his3; LEU2 PGKp-hA2aR 2mu- ori REP3 Ampr] were dcveloped. LT Media: LT (Leu-Trp supplemenced) media is composed of lOOg DIFCO yeast nitrogen base, supplemented with the following: l.Og valine, l.Og aspartic acid, 0.75g phenylalanine, 0. 9g lysine, 0.45g tyrosine, 0.45g isoleucine, 0.3g methionine, 0. 6g adenine, 0.4g uracil, 0.3g serine, 0.3g proline, 0.3g cysteine, 0.3g arginine, O.9g histidine and l.Og threonine. Construcţiei! of Yeast Strains Expres s ing Hunan Aa Adenosine Receptor In this example, the construction of yeast strains expressing a human Ai adenosine receptor functionally integrated into the yeast pheromone system pathway is described. X. Expression Vector Conotruction To constrxict a yeast expression vector for the human Aj adenosine receptor, the A: adenosine receptor cDNA was obtained by reverse transcriptase PCR of human hippocampus mRNA using primers designed based on the published seguence of the human Al adenosine receptor and standard techniques. The PCR product was subcloned into the Ncol and Xbal sites of the yeast expression plasmid pMPIS . The pMPIS plasmid was created f rom pLPXt as follows: The Kbal site of YEP51 (Broach, J.R. et al. (1983) "Vectors for ligh-level, inducible expression of cloned genes in yeast" p. 33-117 in M. Inouye (ed.), Experimental Manipulation of Gene îxpression. Academic Press, New York) was eliminated by digestion, enc-fill and reiigation co -create YepSINccrxba. Another Xbal site was created at the BamHI site by digeste h BamHI, end-fill, linJcer (New England Biolabs, * 1081) ligation, Xbal digestion and re-ligation to generate YEPSINcoXt. This plasmid was digested with Esp3l and Nccl and ligated to Leu2 and PGKp fragments generated by PCR. The 2 kb Leu2 PCR product was generated by atnplification froir. YEPSINco using primers containing Esp31 and BglII sites. The 660 base pair PGKp PCR product was generated by amplification from pPGKas (Kang, Y.-S. et al. (1990) Mol. Ceil. Biol. JLQ.-2582-2590) with PCR primers containing BglII and Ncol sites. The resulting plasmid is called pLPXt. pLPXt was tnodified by inserting the coding region of the a-factor pre-pro leader into the Ncol site. The prepro leader was inserted so that the Ncol cloning site was maintained at the 3' end of the leader, but not regenerated at the 5' end. In this way receptors can be cloned by digestion of the plasmid with Ncol and Xbal. The resulting plasmid is called pMPIS. The pMPIS plasmid into which was inserted the human At adenosine receptor cDNA was designated p5095. In this vector, the receptor cDNA is fused to the 3' end of the yeast a-factor prepro leader. During protein maturation the prepro peptide sequences are cleaved to generate mature full-length receptor. This occurs during processing of the receptor through the yeast secretory pathway. This plasmid is maintained by Leu selection (i.e., growth on medium lacking leucine). The sequence of the cloned coding region was determined and found to be equivalent to that in the published literature (GenBank accession numbers S45235 and S56143). II. Y«a*t Străin Construction To create a yeast străin expressing the human A: adenosine receptor, yeast străin CY7967 was used as the starting parental străin. The genotype of CY7967 is as follows: MATa gpaD1163 gpal(41)Gai3 farlD1442 tbt-1 FUS1-HIS3 câni ste!4::trpl::LYS2 ste3DH56 Iys2 ura3 Ieu2 his3 The genetic markers are reviewed below: MATa Macing type a. gpalD1163 gpal (41)Gai3. farlD1442 tbt -1 ~ FUS1-HIS3.— can l Stel4::trpl:: L YS2-... ste3D1156.. Iys2 . ura3 . Ieu2 crpl. The endogenous yeast G-protein GPAl nas been deleted. gpal (41)-Gai3 was incegrated into the yeasc genome. This chimeric Ga procein is composed of the first 41 am i no acids of che endogenous yeast Ga subunit GPAl fused to the matnmalian G-protein Gai3 in which the cognate N-terminal amino acids have been deleted. FAR1 gene (responsible for cell cycle arrest) has been deleted (thereby preventing cell cycle arrest upon activation of the pheromone response pathway). străin with high transformation efficiency by electroporation. a fusion between the FUS1 promoter and the HIS3 coding region (thereby creating a pheromone inducible HIS3 gene). arginine/canavinine permease. gene disruption of STE14, a C-farnesyl methyltransferase (thereby lowering basal signaling through the pheromone pathway). endogenous yeast STR, the a factor pheromone receptor (STE3) was disrupted. defect in 2-aminoapidate reductase, yeast need lysine to grow. • defect in orotidine-5'-phosphate decarboxylase, yeast need uracil to grow defect in b-isopropylmalate dehydrogenase, yeast need leucine to grow. defect in phosphoribosylanthranilate, yeast need tryptophan to grow. defect in imidazoleglycerolphosphate dehydrogenase, yeast need histidine to grow. Two plasmicis were transformed inco străin CV~5S~ by electroporation: plasmid p5095 (encoding human A: adenosine receptor; described above) and plasmid p!584, which is a FUSl-3-galactosidase reporter gene plasmid. Plasmid pl5S4 was derived from plasmid pRS426 (Christianson, T.w. et al. (1992) Gene lip;119-1122) . Plasmid pRS426 contains a polylinker site ac nucleotides 2004-2016. A fusion between the FUS1 promoter and the &-galactosidase gene was inserted at the restriction sites EagI and Xhol to create plasmid pl584. The p!584 plasmid is maintained by Trp selection (i.e., growth on medium lacking leucine). The resultant străin carrying p5095 and pl584, referred to as CY12660, expresses the human Ax adenosine receptor. To grow this străin in liquid or on agar plates, minimal media lacking leucine and tryptophan was used. To perform a growth assay on plates (assaying FUS1-HIS3), the plates were at pH 6.8 and contained 0.5-2.5 mM 3-amino-l,2,4-triazole and lacked leucine, tryptophan and histidine. As a control for specificity, a comparison with ane or more other yeast-based seven transmembrane receptor screens was included in all experiments. Coastruction of Yeast Strains Expressing Huaan A2a Adenosine Receptor In this example, the construction of yeast strains expressing a hutnan A2a adenosine receptor functionally integrated into the yeast pheromone system pathway is described. Z. Expression Vector Conatniction To construct a yeast expression vector for the human A2a adenosine receptor, the human A2a receptor cDNA was obtained f rom Dr. Phil Murphy (NIH) . Upon receipt of this clone, the A2a receptor insert was sequenced and found to be identical to the published sequence (GenBank accession # S46950) . The receptor cDNA was excised frotn the plasmid by PCR with VENT polymerase and cloned into the plasmid pLPBX, which drives receptor expression by a constitutive Phosphoglycerate Kinase (PGK) protnoter in yeast. The sequence of the .entire insert was once again sequenced and found to be identical with the published sequence. However, by virtue of the cloning strategy employed there were three amino acids appended to the carboxy-terminus of the receptor, GlySerVal. II. Yeast Străin Construction To create a yeast străin expressing the human A2a adenosine receptor, yeast străin CY8342 was used as the starting parental străin. The genotype of CY8342 is as follows: MATa farlD1442 tbtl-1 Iys2 ura3 Ieu2 trpl his3 fusl-HIS3 câni ste3D115S gpaD1163 ste!4::trpl::LYS2 gpalp-rGasE10K (or gpalp-rGasD229S or gpalp-rGasE10K+D229S) The genetic markers are as described in Example l, except for the G-protein variation. For human A2a receptor-expression. yeast strains were utilized in which the endogenous yeast G protein GPA1 hâd been deleted and replaced by a mammalian Gas. Three rât Gas mutants were utilized. These variants contain one or two point mutations which convert them into proteins which couple efficiently to yeast 3y- They are identified as G3.E10K (in which the glutamic acid at position ten is replaced with lysine) , Ga.D229S (in which the aspartic acid az position 229 is replaced wich serine) and Ga.E10K-i-D229S (whicr. contains both point mutations). Străin CY8342 (carrying one of the three mutant rât Gas proteins) was transformed with either the parental vector pLPBX (Receptor") or with pLPBX-A2a (Receptor*). A plasmid with the FUS1 promoter fused to 3-galactosidase codinc sequences (described in above) was added to assess the magnitude of activation of the pheromone resporise pathway. Funcţional Assay using Yeast Strains Expressing Human A: Adenosine Receptor In this example, the development of a funcţional screening assay in yeast for modulators of the human A: adenosine receptor is described. I. Ligands Used in Assay Adenosine, a natural agonist for this receptor, as well as two other synthetic agonists were utilized for development of this assay. Adenosine, reported to have an EC5C of approximately 75 nM, and (-)-N6-(2-phenylisopropyl)-adenosine (PIA) with a reported affinity of approximately 50 nM were used in a subset of experiments. 5'-N-ethylcarboxamido-adenosine (NEGA) was used in all growth assays. To prevent signaling due to the presence of adenosine in the growth media, adenosine deaminase (4U/ml) was added to all assays. II. Biologica! Reaponaa in Yeast The ability of the A, adenosine receptor to functionally couple in a heterologous yeast system was assessed by introducing the A: receptor expression vector (p5095, described above) into a series of yeast strains that expressed different G protein subunits. The majority of these transformants expressed G„ subunits of the Gai or G00 subtype. Additional G0 proteins were also tested for the possible identification of promiscuous receptor-Ga protein coupling. In various strains, a STE18 or a chimeric STE18- (Table Removed) As indicated in Table 3, the mosc robust si gria ling was found co occur in a yeast străin expressing the GPA:(41)-G„i3 chimera. III. fusl-La.cZ Asaay i To characterize activation of the pheromone response pathway more fully, synthesis of 3-galactosidase through fuslLacZ in response to agonist stimulation was measured. To perfortn the 3-galactosadase assay, increasing concentrations of ligand were added to mid-log culture of human Aj adenosine receptor Gy2 construct was integrated into the genome cf the yeasc. The yeasc strains harbored a defective HIS3 gene and ar. incegrated copy of FUS1-HIS3, thereby allowing for seleccion in selective media containing 3-amino-l,2,4-triazole (tested at 0.2, 0.5 and 1.0 înM) and lacking histidine. Transfortnants were isolated and monolayers were prepared on media containing 3-amino-l,2,4-triazole, 4 U/ml adenosine deaminase and lacking histidine. Five microliters of various concentrations of ligand (e. g., NECA at O, 0.1, l. O and 10 mM) was applied. Growth was monitored for 2 days. Ligand-dependent growth responses were tested in this manner in the various yeast strains. The results are summarized in Table l below. The symbol (-) indicates that ligand-dependent receptor activation was not detected while (+) denotes ligand-dependent response. The term "LIRMA" indicates ligand independent receptor mediated activation. expressed in a yeast străin co-expressing a SteiB-GY2 chimera and GPA41-Gai3. Transformants were isolated and growr. ovemight in the presence of histidine and 4 U/ml adenosine deaminase. After five hours of incubation with 4 U/ml adenosine deaminase and ligand, induction of 3-galactosidase was measured using CPRG as the substrate for 3-galactoside. 5 x 10 cells were used per assay. The results obtained with NECA stimulation indicated that at a NECA concentration of 10~ M approximately 2-fold stimulation of 3-galactosidase activity was achieved. Moreover, a stimulation index of approximately 10-fold was observed at a. NECA concentration of 10 M. The utility of this assay was extended by validation of the activity of antagonists on this străin. Two Jcnown adenosine antagonist, XAC and DPCPX, were tested for their ability to compete against NECA (at 5 mM) for activity in the 3-galactosidase assay. In these assays, 3-galactosidase induction was measured using FDG as the substrate and 1.6 x 10 cells per assay. The results indicated that both XAC and DPCPX served as potent antagonists of yeast-expressed A^ adenosine receptor, with IC$Q values of 44 nM and 49 nM, respectively. In order to determine if this inhibitory effect was specific to the A! subtype, a series of complementary experiments were performed with the yeast-based A2a receptor assay (described in Example 4) . Results obtained with the A,a yeast-based assay indicated that XAC was a relatively ef fective A2i receptor antagonist, consistent with published reports. In contrast, DPCPX was relatively inert at this receptor, as expected from published reports. , IV. Radioligand Binding The A: adenosine receptor assay was further characterized by measurement of the receptor's radioligand binding parameters. Displacement binding of [ H]CPX by several adenosine receptor reference compounds, XAC, DPCPX, and CGS, was analyzed usinc memfaranes prepared from yeast expressing the număr; A adenosine receptor. The results with yeast membranes expressing the human Ax adenosine receptor were compared to those from yeast membranes expressing the human A2a adenosine receptor or the human A3 receptor to examine the specificity of binding. To perform the assay, fifty mg of membranes were incubated with 0.4 nM [-H]CPX and increasing concentraticns of adenosine receptor ligands. Incubation was in 50 mM Tris-HC1, pH 7.4, l mM EDTA, 10 mM MgCl2, 0.25 % BSA and 2 U/ml adenosine deaminase in the presence of protease inhibitors for 60 minutes at room temperature. Binding was terminated by addition of ice-cold 50 mM Tris-HCl, pH 7.4 plus 10 mM MgCl2, followed by rapid filtration over GF/B filters previously soaked with 0.5 % polyethyenimine, using a Packard 96-well" harvester. Data were analyzed by nonlinear least square curve fitting procedure using Prism 2.01 software. The 1050 values obtained in this experiment are summarized in Table 4, below: Table 4 (Table Removed) These data indicate that the reference compounds have affinities consistent with those reported in the literature. The data further indicate that the yeast-based assays are of sufficient sensitivity to discriminate receptor subtype specificity. Funcţional Assay using Yeast Scrains Expressing Huna.-. A2s Adenosine Receptor In this exatnple, the development of a funcţional screeninc assay in yeast for modulators of the human A: adenosine receptor is described. I. Ligands Used in Assay The natural ligand adenosine, as well as other thoroughly characterized and commercially available ligands were used for study of the human A2a receptor functionally expressed in yeast.. Three ligands nave been used in the estafclishment of this assay. They include: Ligrand Reportgd J Funccian Adenosine 500 nM agonist 5' -N-ethylcarboxamidoadenosine 10-15 nM agonist (NECA) (-)-N6-(2- phenylisopropyl)-adenosine 100-125 nM agonist (PIA) To prevent signaling due to the presence of adenosine in-the growth media, adenosine deaminase (4D/ml) was added to all assays. II. Biologieal R«spona« in Yeast A2a receptor agonists were tested for the capacity to stimulate the pherotnone response pathway in yeast transformed with the A2a receptor expression plasmid and expressing either GasE10K, GasD229S or GQSE10K-fD229S. The ability of ligand to stimulate the pheromone response pathway in a receptor dependent manner was indicated by an alteration in the yeast phenotype. Receptor activation modified the phenotype from histidine auxotrophy to hilstidine prototrophy C activation of fusl-HIS3) . Three independent transformants were isolated and grown overnight in the presence of histidine. Cells were washed to remove histidine and diluted to 2 x 10 cells/ml. 5 ni of each transformant was spotted onto nonselective media (including histidine) or selective media (l mM AT) in the absence or presence cf 4 u/r.l adenosine deaminase. Plates were grovm at 30 "C for 24 hours. In the presenca of histidine both Receptor" (R") ane Receptor" (R~) strains were capable of growth. However, in the absence of histidine only R* cells grew. Since no ligand hâd been added to these plates two explanations were possibie for this result. One possibie interpretation was that the receptor bearing yeast were at a growth advantage due to Ligand Independent Receptor Mediated Activation (LIRMA). Altematively the yeast could have been synthesizing the ligand adenosine. To distinguish between these two possibilities, an enzyme which degrades the ligand, adenosine deaminase (ADA) , was added to the growing yeast and plates. In the presence of adenosine deaminase R* cells no longer grew in the absence of histidine, indicating that the yeast were indeed synthesizing ligand. This interpretation was confirmed by an A2a growth assay in liguid. In this experiment R"1" yeast (a GQSE10K străin expressing the A2a receptor) were inoculated at three densities (l x IO6 cell/ml; 3 x IO5 cells/ml; or l x IO5 cells/ml) in the presence or absence of adenosine deaminase (4 U/ml) . The stringency of the assay was enhanced with increasing concentrations (O, 0.1, 0.2 or 0.4 mM)of 3-amino-1,2,4-triazole (AT) , a competitive antagonist of imidazoleglycerol-P dehydratase, the protein product of the HIS3 gene. In the presence of adenosine deaminase and 3-amino-l,2,4-triazole yeast grew less vigorously. However in the absence of 3-amino-1, 2,4-triazole, adenosine deaminase hâd little effect. Thus adenosine deaminase itself hâd no direct effect upon the pheromone response pathway. An alternative approach to measuring growth and one that can be miniaturized for high throughput screening is an A2a receptor ligand spot assay. A GQSE10K străin expressing the A2a receptor (A2aR+) or lacking the receptor (R-) was grown overnighc in the presence of histidine and 4 U/ml adenosine deaminase. Cells were washed to remove histidine and diluted to S x 10° cells/ml. l x 10 °cells were spreac selective plates containing 4 U/ml adenosine deaminase ar.d 0.5 or 1.0 mM 3-amino-l,2,4-triazole (AT) and allowed to dry for l hour. 5 /zi of the following reagents were applied to the monolayer: 10 mM adenosine, 38.7 mM histidine, dimethylsulfoxide (DMSO) , 10 mM PIA or 10 mM NECA. Cells were grown 24 hours at 30°C. The results showed that cells without receptor could only grow when histidine was added to the media. In contrast, R* cells only grew in areas where the A2a receptor ligands PIA and NECA hâd been spotted. Since the plates contained adenosine deaminase, the lack of growth where adenosine hâd been spotted confirmed that adenosine deaminase was active. ZII. fus l LacZ Asaay To quantitate activation of the yeast mating pathway, synthesis of 3-galactosidase through fuslLacZ was measured. Yeast strains expressing G„£10K, G^3D229S or G03E10K+D229S were transformed with a plastnid encoding the human A2a receptor (R+) or with a plasmid lacking the receptor (R-) . Transformants were isolated and grown overnight in the presence of histidine and 4 U/ml adenosine deaminase. l x 10 cells were diluted to l x 10 cells/ml and exposed to increasing concentrations of NECA for 4 hours, followed by determination of the 0-galactosidase activity in the cells. The results demonstrated that essentially no (3-galactosidase activity was detected in R- strains, whereas increasing amounts of 0-galactosidase activity were detected in R+ strains expressing either G.„E10K, G3SD229S or G,„E10K+D229S as the concentration of NECA increased, indicating a dose dependent increase in units of (3-galactosidase detected in response to exposure to increased ligand concentration. This dose dependency was only observed in cells expressing the A2a receptor. Furthermore the most potent Gaj construct for the A2a receptor was GOJE10K. The G„D229S construct was the second-most potent G,, construct for the A2a receptor, while the G3SE10Kt-D229S construct was the least potent of the three GaJ consrruccs tested, alchough even the G3.ElOK-r-D225S construct stimuiated readily detectable amounts of 5-galactosidase activity. i For a furchcr description of the assays identifică, see U.S. Application Serial No. 09/088985, entitled "Funcţional Expression of Adenosine Receptors in Yeast", filed June 2, 1998 (Attomey Docket No. CPI-093), the entire contents cf which are hereby incorporated herein by reference. Pharnacological Characterization of the Human Adenosine Receptor Subtypes Material and Methoda Materials. [ H] -DPCPX [Cyclopentyl-l,3-dipropylxantine, 8- [dipropyl-2,3-3H(N)J (120.0 Ci/mmol); [3H]-CGS 21680, [carboxyethyl-3H (N)] (30 Ci/mmol) and ["*!] -AB-MECA (i I]-4-Aminoben2yl-5'-N-Methylcarboxamideoadenosine) (2,200 Ci/mmol) were purchased f rom New England Nuclear (Boston, MĂ). XAC (Xantine amine congener); NECA (5'-N-Ethylcarboxamidoadenosine); and IB-MECA from Research Biocheraicals International (RBI, Natick, MĂ). The Adenosine Deaminase and Complete protease inhibitor cocktail tablets were purchased from Boehringer Mannheim Corp. (Indianapolis, IN). Membranes from HEK-293 cells stably expressing the human Adenosine 2a [RB-HA2a]; Adenosine 2b [RB-HA2b] or Adenosine 3 [RB-HA3] receptor subtypes, respectively were purchased from Receptor Biology (Beltsville, MD). Cell culture reagents were from Life Technologies (Grand Island, NY) except for serum that was from Hyclone (Logan, UT) . Yeast strains: Saccharomyces cerevisiac strains CY12660 [farl*1442 tbtl-l fusl-HIS3 câni ste!4::trpl::LYS2 ste3*1156 gpal (41)-Gai3 Iys2 ura3 Ieu2 trpl: his3; LEU2 PGKp-MfalLeader-hAlR-PHOSterm 2mu-orig REP3 Ampr) and CY8362 [gpalp-rGasElOK farl1442 tbtl-l fusl-HIS3 câni ste!4::trpl: LYS2 ste3*1156 Iys2 ura3 Ieu2 trpl his3; LEU2 PGKp-hA2aR 2mu- ori REP3 Ampr] were developed as described above. Yeast culcare: Transfarmed yeast were grown in Leu-Trp [LTj media (pH 5.4) supplemented with 2% glucose. For the preparation of membranes 250 ml of LT medium were inoculated with start titer of 1-2 x 10 cells/ml from a 30 ml overnight cuiture and incubated at 30°C under permanent oxygenation by rotation. After 16 h growth the cells were harvested by centrifugation and membranes were prepared as described below. Maim&lian Tissue Culcure: The HEK-293 cells stably expressed human Adenosine 2a receptor subtype (Cadus clone # 5) were grown in Dulbeco's minimal essential media (DMEM) supplemented with IOV fetal bovine serum and IX penicillin/streptomycin under selective pressure using 500 mg/ml G418 antibiotic, at 37°C in a humidified 5% C02 attnosphere. yeasc Cel J Membrane Prepara tions: 250 ml cultures were harvested after overnight incubation by centrifugation at 2,000 x g in a Sorvall RT6000 centrifuge. Cells were washed in ice-cold water, centrifuged at 4°C and the pellet was resuspended in 10 ml ice-cold lysis buffer [5 mM Tris-HCl, pH 7.5; 5 mM EDTA; and 5 mM EGTA] supplemented with Protease inhibitor cocktail tablets (l tabiet per 25 ml buffer). Glass beads (17 g; Mesh 400-600; Sigma) were added to the suspension and the cells were broken by vigorous vortexing at 4°C for 5 min. The homogenate was diluted with additional 30 ml lysis buffer plus protease inhibitors and centrifuged at 3,000 x g for 5 min. Subsequently the membranes were peleted at 36,000 x g (Sorvall RC5B, type SS34 rotor) for 45 min. The resulting membrane pellet was resuspended in 5 ml membrane buffer [50 mM Tris-HCl, pH 7.5; 0.6 mM EDTA; and 5 mM MgCl2] supplemented with Protease inhibitor cocktail tablets (l tabiet per 50 ml buffer) and stored at -80 °C for further experiments, Marroalian Cell Membrane Prepara zions: HEK-293 cell membranes were prepared as described previously (Duzic E er aJ. .- J. Biol. Chen»., 267, 9844-9851, 1992) Briefly, cells were washed with PBS and harvested with a rubber policeman. Cells were pelted at 4°C 200 x g in a Sorvall RT6000 centrifuge. The pellet was resuspended in 5 ml/dish of lysis buffer at 4CC (5 mM Tris-HCl, pH 7.5; 5 mM EDTA; 5 rnM EGTA; 0.1 mM Phenylmethylsulfonyl fluoride, 10 mg/ml pepstatin A; and 10 mg/ml aprotinin) and homogenized in a Dounce homogenizer. The cell lysate was then centrifuged at 36,000 x g (Sorvall RC5B, type SS34 rotor) for 45 min and the pellet resuspended in 5 ml membrane buf fer [50 mM Tris-HCl, pH 7.5; 0.6 mM EDTA; 5 mM MgCl2; 0.1 mM Phenylmethylsulfonyl fluoride, 10 mg/ml pepstatin A; and 10 mg/ml aprotinin) and stored at -80 °C for further experiments. The Bio-Rad protein assay kits, based on the Bradford dye-binding procedure, (Bradford, M.: Anal. Biochem. 72:248 (1976)) were used to determine total protein concentration in yeast and mammalian membranes. Adenosine l receptor subtype saturation and competi tion radioligand binding: Saturation and competition binding on membranes from yeast cell transformed with human A! receptor subtype were carried out using antagonist [ H] OPCPX as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl2; 1.0 mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and l protease inhibitor cocktail tabiet/50 ml] at concentrations of 1.0 mg/ml. In saturation binding membranes (50 M9/well) were incubate with increasing concentrations of [ H] DPCPX (0.05 - 25 nM) in a final volume of 100 1 °f binding buffer at 25°C for l hr in the absence and presence of 10 MM unlabeled XAC in a 96-well microtiter plate. In competition binding membranes (50 g/well) were incubate with [3H] DPCPX (1.0 nM) in a final volume of 100 ml of binding buffer at 25°C for l hr in the absence and presence of 10 /iM unlabeled XAC or increasing concentrations of competing compounds in a 96-well microtiter plate. Adenosine 2a receptor subtype competition radicligand binding: Competition binding on membranes from HSK293 cell stably expressing the human A2a receptor subtype were carried out using agonist [ H] CGS-21680 as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl2; 1.0 mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and l protease inhibitor cocktail tabiet/50 ml] at concentrations of 0.2 mg/ml. Membranes (10 /ug/well) were incubate with [3H] CGS-216BO (100 nM) in a final volume of 100 ml of binding buffer at 25°C for l hr in the absence and presence of 50 ;zM unlabeled NECA or increasing concentrations of competing compounds in a 96-well microtiter plate. Adenosine 3 receptor competition radioligand binding: Competition binding on membranes from HEK293 cell stably expressing the human A3 receptor subtype were carried out using agonist [ I] AB-MECA as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl2; l.O mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and l protease inhibitor cocktail tabiet/50 ml] at concentrations of 0.2 mg/ml. Membranes (10 T T C jig/well) were incubate with [I] AB-MECA (0.75 nM) in a final volume of 100 ni of binding buffer at 25°C for l hr in the absence and presence of 10 MM unlabeled IB-MECA or increasing concentrations of competing compounds in a 96-well microtitefcr plate. At the end of the incubation, the A:, A2i and A3 receptor subtypes radioligand binding assays was terminated by the addition of ice-cold 50 mM Tris-HCl (pH 7.4) buffer supplemcnted with 10 mM MgCl2/ followed by rapid filirarior. over glass fiber filters (96-well GF/B UniFilters, Packard! previously presoaked in 0.5* polyethyienimine in a Filtermate 196 cell harvester (Packard). The filcer plates were dried coaced with 50 ni /well scintillation fluid (MicroScir.t-20, PacJcard) and counted in a TopCount (Packard) . Assays were performed in triplicate. Non-specific binding was 5.6 r 0.5%, 10.8 t 1.4 and 15.1 t 2.6 of the total binding in a AIR, A2aR and A3R binding assay, respectively. Adenosine 2b receptor subtype competition radioligand binding: Competition binding on membranes from HEK293 cell stably expressing the human A2b receptor subtype were carried out using AI receptor antagonist [H] DPCPX as a radioactive ligand. Merabranes was diluted in binding buffer [10 mM Hepes-KOH, pH 7.4; containing 1.0 raM EDTA; 0.1 mM Benzamidine and 2 U/ml adenosine deaminase] at concentrations of 0.3 mg/ml. Membranes (15 ^g/well) were incubate with [3H] DPCPX (15 nM) in a final volume of 100 pi of binding buffer at 25°C for l hr in the absence and presence of 10 nM unlabeled XAC or increasing concentrations of competing compounds in a 96-well microtiter plate. At the end of the incubation, the assay was terminated by the addition of ice-cold 10 mM Hepes-KOH (pH 7.4) buffer followed by rapid filtration over glass fiber filters (96-well GF/C UniFilters, Packard) previously presoaked in 0.5% polyethyienimine in a Filtermate 196 cell harvester (Packard). The filter plates were dried coated with 50 pl/well scintillation fluid (MicroScint-20, Packard) and counted in a TopCount (Packard). Assays .were performed in triplicate. Non-specific binding was 14.3 * 2.3% of the total binding. Specific binding of [3H] DPCPX; [3H] CGS-21680 and [125I] AB-MECA was defined as the difference between the total binding and non-specific binding. Percent inhibition of the compounds was calculated against total binding. Competition data were analyzed by iterative curve fitting to a one site model, and Table 5 Ki values for membranes from yeast cells transformed with human A: receptor subtype (Table Removed) Tables 6 through 12 demonstrate the efficacy and structure activity profiles of deazapurines of the invention. Tables 13 and 14 demonstrate select ivi ty can be achieved for human adenosine receptor sites by modulation of the functionality about the deazapurine structure. Table 14 also demonstrates the surprising discovery that the coitipounds set forth therein nave subnanomolar activi ty and higher select ivity for the A2b receptor as compared to the compounds in Table 13.Kt values were calculated from IC50 values (Cheng and Pruscf, Biochem. Pharmacol. 22, 3099-3109, 1973) using the GraphPad Prizia 2.01 software. Rasults primary function of certain cell surface receptors is to recognize appropriate ligands. Accordingly, we determined ligand binding affinities to establish the funcţional integrity of the Adenosine l receptor subtype expressed in yeast. Crude membranes prepared f rom Saccharomyces cerevisiae transformed with human Adenosine l receptor subtype construct exhibited specific saturable binding of [3H] DPCPX with a KD of 4.0 * 0.19 nM. The KD and Bmax value were calculated from the saturation isotherm and Scatchard transformation of the data indicated a single class of binding sites. The densities of adenosine binding sites in the yeast membrane preparations were estimated to 716.8 + 43.4 fmol/mg membrane protein. The pharmacological subtype characteristics of the recombinam: yeast celîs transformed with human Aa receptor subtype were investigated with subtype selective adenosine ligands (XAC. DPCPX; CGS-15943; Compound 600; Compound 1002; NECA, (R)-PIA; IB-MECA and Alloxazine) that competed with [3H] DPCPX in the expected rank order. Displacement curves recorded with these compounds show the typical steepness with all the ligands, and the data for each of the ligands could be modeled by a one-site fit. The apparent dissociation constants estimated for the individual compound from the curves (Table 5) are consistent with value published for the receptor obtained from other sources. TABLE6 Table Removed) (Table Removed) :2-thienyl-2-yl; -C1-H; water solubic: R, and R, are hydrogen:' R, îs 3-fluorophenyl: • " R, is 3-chlorophenyl;7 R, îs 4-pyridyl:' % acuvity :2> 10 Table 14: Profile of Selective A2b Antagonists (Table Removed) TABLE 15. Adenosine A: Receptor Selective Cotr.pour.ds at leasr 10 times more selective than other three subtvoes. (Table Removed) Paaes 176-201 reiate to compounds soecific to the A-. recestcr Summary of the Invention The present invention is also based on compounds which selectively bind to adenosine A2a receptor, thereby treatinc a disease associated with A2a adenosine receptor in a subject by administering to the subject a therapeuticaliy effective arr.ount of such compounds. The disease to be treated are associated with, for example, a central nervous system disorder, a cardiovascular disorder, a renal disorder, an inflammatcry disorder, a gastrointestinal disorder, an eye disorder, an allergic disorder or a respiratory disorder. This invention also features a compound having the structure: (Figure Removed) wherein NRjRz is a substituted or unsubstituted 4-8 membered ring; wherein -A*- is a substituted or unsubstituted four to six membered ring;Rwherein -Rt- is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is C (-Rr) (-R*) XR, wherein X is O, S, or NR wherein ~Rr and -R are each independently H or alkyl, wherein -R- and -R-- are each independently alkyl or cycloalkyl, or -R* and the nitrogen together forrc a substituted or unsubstituted ring of between 4 and 7 members. wherein R is — i-s- K, alkyl, substituted alkyl, or cycloalkyl; with the proviso that NRiR: is not 3-aceramido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl, or pyrrolidino; with the3 proviso that NRiR: is 3-hydroxymethyl piperadino only when -A îs 4-pyridyl. This invention also features a method for inhibiting the activity of an A2a adenosine receptor in a cell, which comprises contacting said cell with the above-mentioned ccmpounds . This invention also provides a compound having the structure: (Figure Removed) wherein NR[R, is a substituted or unsubstituted 4-8 membered ring; l wherein A-f is a substituted or unsubstituted four to six membered ring; wherein -R«- is H, alkyi, substituted alkyl, aryl, arylalkyl, amino, substituted arvl, wherein said are each independently H or alkyl,f wherein -fU- and -R- are each indeoendently alkyl or nitrogen together form a substituted or unsubstituted ring of between 4 and 7 menbers. wherein -Rs- îs H, aikyl, substituted alkyl, or cycloalkyl; with the proviso that NRiR: is not 5-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl, or pyrroiidino; with the proviso that NRiRj is 3-hydroxymechyl piperadino only ? when As is 4-pyridyl. In one embodiment of the compound, -A*- is a substituted or unsubstituted four to six membered ring, phenyl, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1,2,4-triazole, pyridine, 2(1H)-pyridone, 4(1H)-pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, IH-indole, indoline, benzopyrazole, l,3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido[2,3-b]pyrazine, pyrido[3,4-bjpyrazine, pyrido [3, 2-c] pyridazine, purido [ 3, 4 -b] -pyridj|ne, IH-pyrazole[3,4-d]pyrimidine, pteridine, 2(1H)-quinolone, l (2H)-isoquinolone, l,4-benzisoxazine, benzothiazole, cuinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, •benzoxazine, phthalazine, cinnoline, or having a structure: (Figure Removed) wherein Y is carbon or nitrogen; wherein Ra is H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, methoxy, methyl amino, methyl thio; In another embod^ment of the compound, the compound has the structure: (Figure Removed) wherein m is l or 2; wherein RA and RB are each independently be H, -OH,/-CH20H, -CH2CH2OH, -C(-0)NHz, a heteroatom, or -C(=0)NRV' wherein/ -Rj is aryl, substituted aryl, or heteroaryl; wherein -R^ is alkyl, or X-ftf' , wherein X is O, or N and -R^ is substituted alkyl or aryl. In another embodiment of the compound, RiRzN is (D)-2-aninocarbonyl pyrrolidino, (D) -2-hydroxymethyl pyrrolidino, (D;-2-hydroxymethyl-tra;3s-4-hydroxy pyrrolidino, piperazino, or 3-hydroxymechyl piperadino. In another embodiment of the compound, the compound has the structura: (Figure Removed) wherein m is O, l, 2, or 3; wherein Y is O, S, or NR, wherein R is RA or RB; wherein RA and Rs are each independently be H, -OH, -CH20H,/-CHjCKjOH, -C(»0)NH2, a heteroatom, or -C(=0)N«^%^; wherein / -R,^'1 is aryl, substituted aryl, or heteroaryl; wherein -R^ is alkyl, or XRf, wherein X is O, or N and «^ is substituted alkyl or aryl. *u In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (igure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) (Compound 1604) (Figure Removed) In another embodiment of the compound, the compound has the structure: In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structura: (Figure Removed) In yet another embodiment of the compound, the compound has the structure: (Figure Removed) (Figure Removed) In a further embodiment of the compound, the compound has the structure: This invention further provides a compound having the structure (V) : wherein-R-is H, or methyl. In one embodiment of the compound V, the compound nas the structure: (Figure Removed) In another embodiraent of the compound V, the compound has the structure: (Figure Removed) This invention also provides a method for treating a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of compounds IV, or V. In one embodiment of the method, the compound treats said diseases by stimulating adenylate cyclase. In another embodiment of the method, the subject is a mammal. In another embodiment of the method, the mammal is a human. In another embodiment of the method, said A2a adenosine receptor is associated with Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. Diseases associated with adenosine Al, A2a, A2b and A3 receptors are disclosed in WO 99/06053 and WO-09822465, WO-09705138, WO- 09511681, WO-09733879, JP-09291089, PCT/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-soluble prodrug of compounds IV, or V; wherein said water-soluble prodrug that is metabolized in vivo to produce an active drug which selectively inhibit A2a adenosine receptor. In one embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pharmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier. This invention also provides a raethod for inhibiting the activity of an A2a adenosine receptor in a cell, which comprises contacting said cell with compounds IV, or V. In one embodiment of the method, the compound is 'ari antagonist of said A2a adenosine receptor. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. l In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. This invention also provides a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of compounds IV, or V. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, the subject is a human. Ir. another embodiment of the method, the compound is an antagonist of A2a adenosine receptors. This invention further provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of compounds IV, or V. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method, said compound is an antagonist of A2a adenosine receptors. This invention also provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of compounds IV, or V. In one embodiment of the method, said damage comprises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic. In another embodiment of the method, said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of A2a adenosine receptors. This invention also provide a pharmaceutical composition comprising a therapeutically effective amount of compounds IV, or V and a pharmaceutically acceptable carrier. In one embodiment of the pharmaceut_cal composition, said therapeutically effective amount is effective to treat Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a surgical irrigating solution. This invention also provides a combination therapy for Parkinson's disease comprising compounds IV and V, and any of the dopamine enhancers. This invention further provides a combinational therapy for cancer comprising compounds IV and V, and any of the cytotoxic agents. This invention further provides a combinational therapy for glaucoma, comprising compounds IV or V, and a prostaglandin agoni-st, a muscrinic agonist, or a K-2 antagonist. This invention also provides a packaged pharmaceutical composition for treating a disease associated with A2a adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of compounds IV, or V; and (b) instructions for using said compound fer treating said disease in a subject. This invention also provide a method of preparing compound IV, comprising the steps ofreactmg (Figure Removed) wherein P is a removable protecting group; b) treating the product of step a) under cyclization conditions to provide (Figure Removed) c) treating the product of step b) under suitable conditions to provide Figure Removed) treating the chlorinated product of step c) with NHRiR2 to provide (Figure Removed) wherein NRtR, is a substituted or unsubstituted 4-8 membered ring; & wherein A* îs a substituted or unsubstituted four to six membered ring; wherein ftr-is H, alkyl, substituted alkyl, aryl, arylalkyl, amine, substituted aryl, wherein said substituted alkvl is /?7 ty &? fio XV ' £ -C (-fir) (-£*•) XR*, wherein X is O, S, or N-R-r, wherein •««- and -R«- &l £lC are each independently H or alkyl, wherein -R*- and -R* are A,^, A, o each independently alkyl or cycloalkyl, or -R*., -R* and the nitrogen together form a substituted or unsubstituted ring of between 4 and l members. wherein -R-* is H, alkyl, substituted alkyl, or cycloalkyl; with the proviso that NRiRz is not 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl, or pyrrolidino; with the proviso that NRiR? is 3-hydroxymethyl piperadino only when A*- is 4-pyridyl. This invention further provides a method of preparing compound V, comprising the steps of (Figure Removed) a) reacring wherein P is a removable protecting group; b) treating the product of step a) under cyclizarion conditions to provide (Figure Removed) c) treating the produc: of step b) under suitable conditions to provide (Figure Removed) d) treating the chlorinated product of step c) first with dimethylamine and formaldehyde, then with N-methyl benzyiamine and finalry with NH2R.I to provide (Figure Removed) wherein Ri is acetanido ethyl; wherein -Af is 4-pyridyl; wherein -ft-^is H, or methyl; wherein -Rs- is N-methyl-N-benzyl aminomethyl . As used herein, "A compound is A2a selective." means that a compound has a binding constant to adenosine Aza receptor of at least five time higher then that to adenosine Alt A2b, or A3. The invention is further illustrated by the following exampies which in no way should be construed as being further limiting. The contenta of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the exampies are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. This invention will be better understood from the Experimental Details which follow. However, one skilled in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. Exanple 22: Synthesis of Adenosine Aj. Antagonista, compound* 1601, 1602, and 1603. (Figure Removed) Compound 26 (10.93g, 50.76 mmol) was dissolved in DMF (67 mL). 4-Amidinopyridine hydrochloride (8.0g, 50.76 mmol) and DBU (15.4 g, 101.5 mmol) were added sequentially and the reaction was heated to 85°C. After 22 hours, the reaction was cooled to room temperature and the DMF was removed in vacuo. The dark oii was diluted with 2M HC1 (80 mL). The reaction was allowed to stand. After 2 hours, the solution was cooled to 10°C and filtered. The solid was washed with cold water and dried to yield 7.40g of a yellow solid, compound 27 (69%). 'H-NMR (200MHZ, d6-DMSO) d 6.58 (s, 1H) , 7.27 (s, 1H), 8.53 (d, 2H, J = 5.6), 9.00 (d, 2H, J = 5.2Hz), 12.35 (brs, 1H) . MS (ES) : 212.8 (MT+1) . Compound 27 (7.4 mmol, 29.8 mmol) was diluted with POC13 and heated to 105°C. After 18 hours, the reaction is cooled to room temperature and the POC13 is removed in vacuo. The thick dark oii is diluted with MeOH (75mL) followed by ether (120mL). The amorphous red solid is filtered and washed with ether to yield 3.82 g of a red solid. The crude solid, compound 28, is approximately 80% pure and used without further purification in the next reaction. 'H-NMR (200MHz, d6-DMSO) d 6.58 (s, 1H) , 7.27 (s, 1H), 8.53 (d, 2H, J = 5.6), 9.00 (d, 2H, J « 5.2Hz), 12.35 (brs, 1H). MS (ES): 212.8 (M*+l). Compound 1601: DMSO (5 mL) and D-prolinol (500mg, 4.94 mmol) were added to compound 28 (500mg, 2.17 mmol) was added. The reaction was heated to 120°C. After 18 hours, The reaction was cooled to room temperature and diluted with EtOAc and H20. The layers were separated and the aqueous layer was extracted with EtOAc (2x). The combinqd organic layers were washed with H2O (2x), brine, dried over MgSO2 filtered and concentrated to yield 200mg of a tan solid. The solid was recrystallized from EtOAc to yield 82 mg of a tan solid (13%). 1H-NMR (200 MHz, d6-DMSO) d 2.05 (m, 4H), 3.43 (m, 1H) , 3.70 - 4.00 (m, 3H), 4.50 (brs, 1H), 4.92 (brs, 1H), 6.62 (m, 1H), 7.22 (m, 1H) , 8.22 (d, 2H, J - 6.0 Hz), 6.64 (d, 2H, J = 6.2 Hz), MS (ES) : 296.0 (MT+1), mp = 210 - 220°C (decomp.). Compound 1602: Chromatography (silica, 9:1 CHCl3/MeOH) yielded 10 mg of a tan solid (2%).1H-NMR (d6-DMSO) d 2.00 - 2.50 (m, 4H), 4.05 (m, 1H), 4.21 (m, 1H), 6.71 (d, 1H, J = 3.2 Hz), 7.18 (d, 1H, J = 3.2 Hz), 8.37 (d, 2H, J = 4.8 Hz), 8.56 (d, 2H, J = 5 .0 Hz). MS (ES) : 309.1 (M*+l). Compound 1603. Chroraatography (silica, 20:1 Hexanes /EtOAc) yielded 135 mg of a tan solid (53%). 'H-NMR (d6-DMSO) d 2.00 (m, 4H) , 3.43 (brs, 1H), 3.74 (brs, 2H), 3.87 (brs, 1H), 4.49 (brs, 1H), 4.93 (m, 1H) , 6.56 (m, 1H), 7.12 (m, 1H), 7.40 (m, 3H), 8.34 (m, 2H), 11.62 (brs, 1H). MS (ES): 295.1 (M*+l). Compound 1605. Into a 50mL RBF 60mg of 2- (4' -pyridyl) -4-Chloropyrimidinopyrrole HCl salt was dissolved in 2mL anhydrous DMSO. 3-(R)-Hydroy-(D)-prolinol TFA salt (380mg) and 500mg sodium bicarbonate were added thereto. The mixture was then flashed with nitrogen gas for 5min and heated to 130°C. After 2 hours, the reaction was cooled to .room temperature and the DMSO was removed in vacuo. The residue was partitioned between EtOAc (15mL) and saturated sodium bicarbonate aqueous solution (15mL). The organic layer was separated and washed with brine (15mL) and dried over Na2SO«. After removal of solvent, the crude product was purified by preparative TLC (CH2Cl2/MeOH = 95/5) to yield 35 mg (50%). 'H-NMR (2jOOMHz, CDC13) ( 2.3-2.5 (1H), 3.4-3.8 (3H), 4.4-4.6 (2H), 6.4 (1H); 7.1 (1H); 8.2 (d, 2H); 8.7 (d, 2H); 11.0 (1H). MS (ES): 312 (NT+1). Example 23: Synthesis of Adenosine A;. Antagonist, compound 1606. (Figure Removed) Compound 28 (200mg) was treated with DMF (30mL), (, (-dimethylglycine methyl ester (73mg HC1 salt in 2mL water) and SOOmg sodium bicarbonate. After 18 hours, the DMF was removed in vacuo. The residue was partitioned between EtOAc (30mL) and saturated sodium bicarbonate aqueous solution (15mL) . The organic layer was washed with brine (15mL), dried over sodium sulfate, filtered and concentrated. Chromatography (silica, 10:4 hexanes/EtOAc) yielded 150mg of pure product, compound 29 (69%). 1H-NMR (200MHZ, CDC13) , ( 1.4 (s, 6H) , 3.8 (s, 3H) ; 3.9 (s, 2H); 6.4 (s, 1H) ; 7.4-7.5 (m, 3H) ; 8.4 (m, 2H) ; 9.8 (s, 1H) . Compound 1606: Procedura is the same as Compound 1605 (72%) . :H-NMR (200MHz, CDC13), ( 1.3 (s, 6H), 1.7-1.9 (m, -2H); 2.05-2.30 (m, 2H) ; 3.6-4.1 (m, 11H); 4.80-4.95 (m, 1H) ; 6.4 (s, 1H); 7.4-7.6 (m, 3H) ; 8.3-8.4 (d, J - 8.5 Hz, 2H) , 10 (s, 1H). MS (ES): 424.0 The following compounds can be synthesized in the same manner. Compound 1600: (51%). MS (ES): 326.0 (M*+l).Compound 1607: 1H-NMR (200MHz, CDC13) , ( 1.40 - 1.80 (m, 5H) , 2.80 - 3.50 (m, 3H) , 4.60 - 4.80 (m, 3H) , 6.66 (d, 1H, 'J -6.2HZ), 7.26 (m, 1H), 8.21 (d, 2H, J = 6.3Hz), 8.65 (d, 2H, J - S.BHz), 11.90 (s, 1H) . MS (ES): 310.1 (M'+l). Compound 1608: (64%). aH-NMR (200MHz, d6-DMSO) , ( 1.75 (s, 3H), 2.11 (s, 3H), 2.29 (s, 3H), 3.56 (m, 6H), 7.23 - 7.41 (m, 5H] , 8.00 (brs, 1H), 8.23 (d, 2K, J - 6.0Hz), 8.63 (d, 2H, J = 5.4 Hz), 8.82 (brs, 1H), 11.56 (brs, 1H). MS (ES): 444.0 (M'+l). Compound 1604: :H-NMR (200MHz, CD3OD) ( 3.40 (m, 4H) , 4.29 (m, 4H), 6.99 (s, 1H), 7.5 - 7.2 (m, 3H) , 7.90 (d, 2H), 8.39 (d, 2H), 8.61 (d, 2H). MS (ES): 357.0 (M* +1). TABLE 16. Adenosine A2a Receptor Selective Compounds At least 5 times more selective than other three subtypes (Table Removed) Paoes 202-256 reiate tocompounds specific te the A-, receptor Summarv of the Invention The presant invention is also based on compounds which selectively bind to adenosine A3 receptor, thereby treating a disease associated with A3 adenosine receptor in a sub-ect by administering to the subject a therapeuticaily effective amount of such compounds. The disease to be treated are associated with, for exampie, asthma, hyperser.sitivity, rhinitis, hay fever, serum sickness, allergic vasculitis, atopic dermaytitis, dermaatitis, psoflsis, eczema, idiopathic pulmonary fibrosis, eosinophil/ic chlorecystitis, chronic airway inflammation, hypereosinophilic syndromes, eosinophilic gastroenteritis, edema, urticaria, eosinophilic myocardial disease, episodic angioedema with eosinophilia, inf lanunatory bowel disease, ulcerative colitis, allergic granulomatosis, carcinomatosis, eosinophilic granuloma, familial histiccytosis, hypertension, mast cell degranulation, tumor, cardiac hypoxia, cerebral ischemia, diuresis, renal failure, neurological disorder, mental disorder, cognitive disorder, myocardial ischemia, bronchoconstriction, arthritis, autoimmune disease, Crohn's disease, Grave's disease, diabetes, multiple sclerosis, anaemia, psoriasis, fertility disorders, lupus erthyematosus, reperfusion injury, brain arteriole diameter, the release of allergic mediators, scleroderma, stroke, global ischemia, central nervous system disorder, cardiovascular disorder, renal disorder, inflammatory disorder, gastrointestinal disorder, eye disorder, allergic disorder, respiratory disorder, or immunological disorder. This invention also features a compound having the structura: (Table Removed) wherein Ri is H and R: is cyclopropyl methylamino carbonylechyl, cis-3-hydroxy cyclopentyl, acetamido butyl, methylamino carbonylamino butyl, ethylamino carbonylamino propyl, methylamino carbonylamino propyl, 2-acetyl amino- 3-rnethyl butyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3- hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, l-(R)-phenyl-2- hydroxyethyl, N-methylaminocarbonyl pyridyl-2- methyl, or Ri, Rj and the nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino,' 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein RJ is a substituted or unsubstituted four to six menbered ring, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, l,2,4-triazole, pyridine, 2(1H)- pyridone, 4 (1H)-pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, cxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran,benzothiophene, indole, 2,3-dihydroindole, IH-indole, indoline, benzopyrazole, l, 2-ber.:odioxole, benzoxazoie, purine, coumarin, chromone, quincline, tetrahydroquinoiine, isoquinoline, bennraidazole, quinazoline, pyrido[2,3-b]pyrazine, pyriao[3, 4-b]pyrazine, pyrido[3,2-c]pyridarine, purido f 3, 4-b] -pyridine, l.H-pyrazole[3,4-dJpyrimidine, pteridine, 2(1Hj-quinolone, l(2H)-isoquinolone, l,4-benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinolir.e-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phthalazine, or cinnoline. wherein -Rs- is H, alkyl, substituted alkyl, or cycloalkyl; A wherein -R* is H, alkyl, substituted alkyl, aryl, or substituted aryl. This invention also features a method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting said cell with the above-mentioned compounds. typical practice and is known to those skilled in the art. Typical synthetic schemes for the preparation of deazapurine intermediates of the invention are outlined below in Scheme I. This invention also provides a method of preparing compound IV, comprising the steps of (Figure Removed)) b) wherein P is a removable proteciing group; treating the product of step a) under cyclizatton conditions to provide (Figure Removed) c) treating the product of step b) under suitable conditions to provide (Figure Removed) d) treating the chlorinated product of Step c) with NHRiRj to provide (Figure Removed) wherein R: is K and R: is cyclopropyl methyianunc carbonylethyl, cis-3-hydroxy cyciopenryl, acetamido butyl, methylamino carbonylaninc butyl, erhylamino carbonylamino propyl, methylamino carbonylaminc propyl, 2-acetyl aminc- 3-methyl butyl, K,N-diethylamino carbonylamino ethyl, thioacetarr.ido ethyl, 3-amino acetyloxy cyclopentyl, 3- . hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, l-(R)-phenyl-2- hydroxyethyl, N-methylam.nocarbonyl pyridyl-2- methyl, or Ri, RJ and the nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein Ra is a substituted or unsubstituted four to six membered ring;& wherein is H, alkyl, substituted alkyl, or cycloalkyl; wherein ft- is H, alkyl, substituted alkyl, aryl, or substituted aryl. This invention also provides a method of preparing compound of V, comprising the steps of (Figure Removed) b) wherein P is a removable protecting croup; treating the product of step a) under cyclization conditions to provide (Figure Removed) c) treating the product of step b) under suiuble conditions to provide (Figure Removed) ; and d) treating the chlorinated product of step c) with NH2CH2(CH2)mCH2NHC(-O)Ri to provide NH2CH2(CH2)mCH2NHC(-O)R l wherein m is O, l, or 2; wherein R: is cyclopropyl methyl, methyl, methylamino, or aminomethyl; wherein -R- i s aryl, substituted aryl, heteroaryl; wherein -Rs- is H, alkyl, substituted alkyl, or cycloalkyl; wherein -R, is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C (-R (RNR Rs, wherein -R- and -Rw are , each H or alkyl, wherein -R*- and -Re- are each alkyl or cycloalkyl, or -R -R- and the nitrogen together form a & f\ cycloalkyl, or -R, -R»- and the nitrogen ring system of between 4 and 7 members. This invention further provided a method of preparing compound VI, comprising a) reacting b) (Figure Removed) to provide wherein P is a removable protecting group; b) treating the product of step a) under cyclization conditions to provide (Figure Removed) c) treating the product of step b) under stiitable conditions to provide d) treating the chlorinated product of step c) with HN to provide(Figure Removed) wherein ^R-f is unsubstituted aryl. -wherein .Rr is H, alkyl, substituted aikyl, or cycloalkyl; wherein &f H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substi-uted aryl, wherein said substiiuced alkv" is wherein -R- and -Re-are each alkyl cr cycloalkyi, or -ftr, -R» and the nitrogen together form a ring system of between 4 and 7 members . This invention also provides a compound having the structure: (Figure Removed) wherein Ri is H and Rz is cyclopropyl methylamino carbonylethyl, cis-3-hydroxy cyclopentyl, acetamido butyl, methylamino carbonylamino butyl; ethylamino carbonylamino propyl, methylamino carbonylamino propyl, 2-acetyl amino-3-methyl butyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3-hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2-imidazolidinone echyl, l-aminocarbonyl-2-methyl propyl, 1-aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2-imidazolyl ethyl, acetamido ethyl, l-(R)-phenyl-2-hydroxyethyl, N-methylaminocarbonyl pyridyl-2- methyl, or R;, R: and rhe nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonyimethyl pyrrolidino, 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein R: îs a subsrituted or ur.substi tutec benzene, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1,2, 4-triazole, pyridine, 2 (1H) -pyridone, 4 ( 1H) -pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazcle, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, 1H- indole, indoline, benzopyrazole, l, 3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido[2, 3-b] pyrazine, pyrido[3, 4-b] pyrazine, pyrido[3,2-c]pyridazine, purido (3, 4-b] -pyridine, 1H-pyrazole [3, 4-d]pyrimidine, pteridine, 2 (1H) -quinolone, l (2H) -isoquinolone, l, 4-benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phthalazine, or cinnoline. h . wherein is H, alkyl, substituted alkyl, or cycloalkyl; wherein JRf is H, alkyl, substituted alkyl, aryl, or substituted aryl .In one embodiment of the compound, structure: (Figure Removed) In another embodiment of the compound. R: is pher.yl. In another embodiment of the compound, hydrogen or ethyl. A-In another embodiment of the compound, -ju- i s hydrogen, methyl, phenyl, 3-chlorophenyloxy methyl, or trans-2- phenylamino methyl pyrrolidino methyl. This invention further provides a compound having the structure: (Figure Removed)wherein m is O, l, or 2; wherein Ri is cyclopropyl methyl, methyl, methylamino, or aminomethyl; wherein -Rr is aryl, substituted aryl, or heceroarvl; wherein 4Z* i s H, alkyl, substituted alkyl, or cycloalkyl;wherein -R- is H, alkyl, substicuted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C (•£*} (-Rw) NR-fft-i, wherein 9 and -Rt are .I each H or alkyl, wherein -fi* and -fir are each alkyl or r^tţ '\fQ cycloalkyl, or -R*, -fi» and the nitrogen togerher form a ring system of between 4 and 7 menbers. /T In one embodiment of compound V, m is O and -R* is phenyl. In another embodiment of compound V, m is l and-R* is phenyl. In another embodiment of compound V, m is 2 and -te is phenyl. In another embodiment of compound V, Rs and Re are methyl. In another embodiment of compound V, Rs and Re are methyl. In another embodiment of compound V, Rs and Re are methyl. In another embodiment of compound V, the compound has the structure: (Figure Removed) In another embodiment of compound V, the structure: compound nas the (Figure Removed) In another embodiment of compound V, the compound has the structure: (Figure Removed) In another embodiment of compound V, the compound has the structure: (Figure Removed) In another embodiment of compound V, the structure: Figure Removed) This invention further provides a compound having the structure: (Figure Removed) ThiS invention also provides a compound having the structura; (Figure Removed) wherein -R is unsubstitutec aryl. wherein $4 i s H, alkyl, substituted alkyl, or cycloalkyl; wherein -R* H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein sr.id substituted alkyl is wherein -R- and -R are each alkyl or cycloalkyl, or -Kr, -R» and the nitrogen together form a ring system of between 4 and 7 members. In one embodiment of compound VI, the compound has the structure: (Figure Removed) In one embodimenc of compound 1309, the structure: compound nas the (Figure Removed) In another embodiment of compound 1309, the structure:compound nas the (Figure Removed) This inventior. also provides a compound having the structura (Figure Removed) wherein R- is 3-hydroxy cyclopentyi ethylamino carbonylamino propyl, N, N-diethylamino carbonylsmino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3-hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2-imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1-aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2-imidazolyl ethyl, acetamido ethyl, l- (R) -phenyl-2-hydroxyethyl, or N-methylaminocarbonyl pyridyl-2- methyl; wherein and $4 are independently H, substituted or unsubstituted alkyl, or aryl. In one embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has thestructure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) in another embodiment of the compound, the compound has the ;tructure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structura: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiraent of the compound, the compound has the structure: In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) This invention also provides 3 ccmpour.c having the structura: (Figure Removed) wherein R:, R and the nitrogen together are 3-hydroxy pyrrolicino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl pyrroiidino, or 3-hydroxymethyl piperadino; wherein Rf and Rf are independently H, substituted or unsubstituted alkyl, or aryl. In one embodiment of the compound, the compound nas the structure : (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: In another embodiment of .the compound, the compound has the structura: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) In another embodiment of the compound, the compound has the structura: (Figure Removed) In another embodiment of the compound, the compound has the structure: (Figure Removed) This invention also provides a method for treating a disease associated with A3 adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of any of the compounds IV, V, VI, VI, or VIII. In one embodiment of the method, the sucject is a mammal. In another embodiment of rhe method, the mammal is 2 human. In another embodiment of the method, said A3 adenosine receptor is associated with a central nervous system discrder, a cardiovascular disorder, asthma, hypersensicivity, rhinitis, hay fever, serum sickness, allercic vasculitis, atopic dermaitaitis, dermaaititis, psorasis, eczema, idiopathic pulmonary fibrosis, eosinophil/ic cnlorecystitis, chronic airway inflairiT.ation, hypereosinophilic syncirones, eosinophilic gastroenceritis, ederna, urticaria, eosinophilic myocardial disease, episodic angioedema with eosinophilia, inflammatory bowel disease, ulcerative colitis, allergic granulomatosis, carcinomatosis, eosinophilic granuloma, familial histiocytosis, hypertension, mast cell degranulation, rumor, cardiac hypoxia, cerebral ischemia, diuresis, renal failure, neurological disorder, mental disorder, cognitive disorder, myocardial ischemia, bronchoconstriction, arthrit;.s, autoimmune disease, Crohn's disease, Grave's disease, diabetes, multiple sclerosis, anaemia, psoriasis, fertility disorders, lupus erthyematosus, reperfusion injury, brain arteriole diameter, the release of allergic mediators, scleroderma, scroke, global ischemia, central nervous system disorder, cardiovascular disorder, renal disorder, inflammatory disorder, gastrointestinal disorder, eye disorder, allergic disorder, respiratory disorder, or immunological disorder. Diseases associated with adenosine Al, A2a, A2b and A3 receptors are disclosed in WO 99/06C53 and WO-09622465, WO-OS705138, WO-09511681, WQ-09733379, JP-09291089, PCT/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-solubie prodrug of any of the compounds IV, V, VI, VII, or VIII; wherein said water-solubie prodrug that is metabolized in vivo to an active drug which selectively inhibit A3 adenosine receptor. In one embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pnarmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier. This invention also provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting said cell with any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, the compound is an antagonist of said A3 adenosine receptor. In another embodiment of the pharmaceutical composition, said pharmaceutical composition -is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. This invention also provides a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of any of the compounds IV, V, VI, Vii, or VIII. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of A3 adenosine receptors. This invention further provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method,, said compound is an antagonist of A3 adenosine receptors. This invention also provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, said damage comprises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic. In another embodiment of the method, said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of A3 adenosine receptors. This invention also provide a pharmaceutical composition comprising a therapeutically effective amount of any of the compounds IV, V, VI, VII, or VIII and a pharmaceutically acceptable carrier. In one embodiment of the pharmaceutical composition, said therapeutically effective amount is effective to treat a respiratory disorder or a gastrointestinal disorder. In another embodiment of the pharmaceutical composition, said gastrointestinal disorder is diarrhea. In another embodiment of the pharmaceutical composition, said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a syscemic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a surgical irrigating solution. This inventio also provides a packaged pharmaceutical composition for treating a disease associated with A3 adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of any of the cornpounds IV, V, VI, VII, or VIII; and (b) instructions for using said compound for treating said disease in a subject. Compounds represented by the formula IV, V, VI, VII, and VIII can be synthesized by the Schemes I-IX. As used herein, "A compound is A3 selective." means that a compound nas a binding constant to adenosine A3 receptor of at least ten time higher then that to adenosine A,, A2a/ or A2b. The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, ciced throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. A skilled artisan will know that metabolism of the compounds disclosed herein in a subject produces certain bioiogically active metabolites which can serve as drugs. This invention will be better understood frora the Experimental Details which follow. However, one skilled in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. Example 24: Adenosine A3 Antagonist Experimentala Compound 1700 (Table 17 below): MS (ES): 366.1 (M*+l). Compound 1710 (Table 17 below): MS (ES;: 381.1 (M*+l). Compound 1316 (Table 17 below): MS (ES): 353.2 (M*+l). Compound 1703 (Table 17 below): MS (ES): 357.1 (M'+l). Compound 1719 (Table 17 below): 'H-NMR (200MHz, d6-DMSO) ( 1.75 (m, 2H), 3.11 (m, 2H) , 3.35 (s, 3H) , 3.59 (m, 2H) , 5.72 (m, 1H), 5.96 (m, 1H), 6.55 (s, 1H) , 7.15 (s, 1H), 7.49 (m, 2H), 8.32 (m, 2H). Compound 1704 (Table 17 below): MS (ES): 367.0 (M'+l). Compound 1706 (Table 17 below): 'H-NMR (200MHz, CDC13) d 1.22 (m, 2H), 1.60-2.40 (m, 4H) , 4.53 (m, 1H), 4.94 (m, 1H) , 5.70 (d, 1H, J = 8.2 Hz), 6.35 (d, 1H, J 2.8 Hz), 6.97 (d, 1H, J = 2.0 Hz), 7.50 (m, 3H), 8.40 (m, 2H), 10.83 (brs, 1H). Compound 1707 (Table 17 below): MS(ES): 347.0 (M*-H). (Table Removed) MS (ES) : 477.1 (M'+l). Compound 1717 (Table 17 below) : H-NMR (200MHz, CD?OD) d 1.69 (m, 1H), 2.26 (m, 1H), 2.42 (d, 2H, J = 7.4Hz), 2.72 (m, 1H), 3.53 (m, 1H), 3.83 (m, 1H) , 4.02 (m, 1H), 4.14 (dd, 1H, J = 10.6, 7.0HZ), 5.14 (2, 2H) , 6.69 (s, 1H) , 6.96 (m, 2H), 7.06 (m, 1H), 7.25 (dd, 1H, J-S.OHz), 7.39 (m, 3H), 8.35 (m, 2H) . MS (ES) : 462.2 (M*+l) . Compound 1718 (Table 17 below) : -NMR (200MHz, CD3OD) d 1.40 - 2.00 (m, 5H), 3.52 (d, 2H, 7.6Hz), 3.80 - 4.00 (m, 1H), 4.00 - 4.20 (m, 3H), 4.50 (m, 2H) , 6.36 - 6.50 (m, 2H) , 6.54 (s, 1H), 6.84 - 6.92 (m, 1H), 7.05 (t, 1K, J - 8.2Hz), 7.30 - 7.45 (m, 3H), 8.24 (d, 2H, J = 9.8Hz). MS (ES): 449.0 (M+l).TABLE 17. Adenosine A3 Receptor Selective Compounds at least io times more selective than other three subtypes. (Table Removed) This invention provides a compound having the structure: (Figure Remove) This invention also provides a compound having the structure (Figure Removed) This invention further provides a compound having th This invention also provides a compound having the structure: (Figure Remove) This invention further provides a compound having the structure: (Figure Remove) This invention also provides a compound having the structure: (Figure Remove) This invention also provides a compound having the structure: This invention further provides a compound having the structure: (Figure Remove) This invention also provides a compound having the structure: (Figure Remove) This invention further provides a compound having the structure: (Figure Remove) This invention further provides a compound having the structure: (Figure Remove) 1515 This invention also provides a compound having the structure (Figure Remove) 1517 This invention further provides a compound having the structure: (Figure Remove) This invention also provides a compound having the structure: (Figure Remove) This invention further provides a compound having the structure: (Figure Remove) In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above method, wherein the subject is a mammal. In a further embodiment the invention provides the above method, wherein the mammal is a human. In a further embodiment the invention provides the above method, wherein said Ai adenosine receptor is associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, or ulcerative condition.In a further embodiment the invention provides a water-soluble prodrug of compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, wherein the water-soluble prodrug is metabolized in vivo to produce an active drug which selectively inhibits Ai adenosine receptor. In a further embodiment the invention provides, wherein said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. In a further embodiment the invention provides a pharmaceutical composition comprising the above prodrug and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a method for inhibiting the activity of an Ai adenosine receptor in a cell, which comprises contacting the cell with compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a cell, wherein the compound is an antagonist of the Ai adenosine receptor. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a cell, wherein the cell is human cell. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a human cell, wherein the compound is an antagonist of Ai adenosine receptors.In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein said disease is aschma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein said disease is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder and wherein the subject is a human. In a further embodiment the invention provides a method for treating the above disease, wherein said compound is an antagonist of Ai adenosine receptors. In a further embodiment the invention provides a combination therapy for asthma, comprising the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, and a steroid, p2 agonist, glucocorticoid, lucotriene antagonist, or anticolinergic agonist. In a further embodiment the invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a method for treating a respiratory disorder with the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514|, 1516, 1517, 1518, 1519, or 1520, wherein said respiratory disorder is aschma, allergic rhinitis, or chronic obstructive pulmonary disease. In a further embodiment the invention provides the above pharmaceutical composition (s) , wherein said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In a further embodiment the invention provides the above pharmaceutical composition (s) , wherein said pharmaceutical composition is a systemic formulation. In a further embodiment the invention provides the above pharmaceutical composition(s) , wherein said pharmaceutical composition is a surgical irrigating solution. In a further embodiment the invention provides a packaged pharmaceutical composition for treating a disease associated with Ai adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520; and (b) instructions for using said compound for treating said disease in a subject. In a further embodiment the invention provides a pharmaceutically acceptable salt of the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above pharmaceutically acceptable salt, wherein the pharmaceutically acceptable salt of the compound 1509, 1511, 1515, 1518, or 1519 contains a cation selected from the group consisting of sodium, calcium and ammonium. In yet a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein the Ai adenosine receptor is associated with congestive heart failure. Exemplification Example 21: Synthesis of i-[6-(4-Hydroxy-4-phenyl-piperidin-l- yl-methyl)-2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidine-2-carboxylic acid amide (1505). Compound 1505 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with L-prolineamide and 4-phenyl-piperidin-4-ol to obtain: (Figure Remove) (d6-DMSO) d 1.53 (s, 1H) , 1.60 (s, 1H) , 1.84-2.30 (m, 6H), 2.66 (m, 2H), 3.60 (s, 2H) , 3.88 (m, 1H), 4.02 (m, 1H), 4.66 (d, 1H, J - 6.8Hz), 4.73 (s, 1H), 6.44 (s, 1H), 6.94 (s, 1H), 7.12 - 7.50 (m, 10H) , 8.35 (m, 2H) , 11.6 (brs, 1H); MS (ES) : 305.1 (M*+l); mp = 234-235°C. Example 22: Synthesis of [N-(2-Phenyl-7H-pyrralo [2, 3-d]pyrimidin-4-yl) (L)-prolinamide (1506) Compound 1506 was synthesized using synthesis scheme VII with L-prolineamide to obtain: (Figure Remove) LH-NMR (DMSO-dJ d 2.05 (m, 4H) , 3.85 (m, 1H) , 4.05 (m, 1H) , 4.70 (d, 1H, J-8.0Hz), 6.58 (brs, 1H), 6.95 (brs, 1H), 7.15 (d, 1H, J=3.4Hz), 7.40 (m, 3H) , 7.50 (brs, 1H), 8.40 (m, 2H), 11.6 (brs, 1H); MS (ES): 308.3 (M*-H). mp= 236-238°C. Example 23: Synthesis of [N- (2-phenyl-6-methoxymethyl-7tf- pyrrolo[2,3-d]pyrimidin-4-yl)-(L)-prolinamide (1507) Compound 1507 was synthesized using precursor compound 23 of synthesis scheme IX to obtain: (Figure Remove) Eromide 23 (4.23g, lOmmol) is dissolved in anhydrous methanol (60mL) and DCM (120mL) and treated with AgO:CCF; under N: at rt for Ih. The solid is removed by filtration and washed with DCM (2x20mL). The filtrate is concentrated in vacuo. The residue is redissolved in DCM (80mL). The resulted solution is then washed with saturated NaHC03 solution and brine, dried over MgSO,, filtered and concentrated to give 3.71g (4, 99%) off white solid. 'H-NMR (CDC13) d 1.75 (s, 9H) , 3.51 (s, 3H) , 4.83 (s, 2H), 6.70 (s, 1H), 7.47 (m, 3H) , 8.52 (m, 2H) . (Figure Remove) Aryl chloride 4 (2.448g, 6.55mmol), DMSO (15mL), L-prolineamide (4.0g, 35.0nunol) and NaHC03 (2.9g) are combined and heated to 120°C under nitrogen. After 4h, the reaction is cooled to room temperatura and diluted with water (60ml). The resulted slurry is extracted with DCM (lOx) . The combined organic layers are washed with saturated NaHC03 solution' and brine, dried over MgSO«, filtered and concentrated to give 2.48g brown solid. Pure product (1.86g, 81%) is obtained after flash column as white solid. White crystals are gotten from THF/hexane. M.p. - 213-215°C. 'H-NMR (CDC13) d 2.15 (m, 3H) , 2.52 (m, IH) , 3.26 (s, 3H), 3.92 (m, IH), 4.10 (m, IH), 4.42 (s, 2H), 5.08 (d, 1H, J=8.2Kz), 5.49 (brs, IH), 6.48 (s, IH), 7.08 (brs, IH), 7.42 (m, 3H), 8.38 (m, 2H), 9.78 (brs, IH); MS (ES): 352.2 (M*+l). Exanple 24: Synthesis of 4-Hydroxy-l-(2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidine-2-carboxylic acid amide (1508) Compound 1508 was obtained with synthesis scheme VII using cis-hydroxy prolineamide to obtain: (Figure Remove) 'H-NMR (d6-DMSO) d 1.90 (m, 1H), 3.85 (d, 1H, J = 9.2Hz), 4.08 (m, 1H), 4.37 (s, 1H), 4.67 (dd, 1H, J = 8.8, 4.0Hz), 5.30 (s, 1H) , 6.55 (s, 1H), 7.15 (s, 2H) , 7.37 (m, 3H), 7.64 (s, 1H) , 8.37 (m, 2H), 11.65 (brs, 1H); MS (ES): 324.2 (M*+l); mp - 268-271°C. Example -25: Synthesis of 3-[4-((S)-2-Carbamoyl-pyrrolodin-l-yl) -2-phenyl-7H-pyrrolo [2, 3-d] pyrimidin-6-yl] -propionic acid (1509) Compound 1509 was obtained using precursor compound 23 of synthesis scheme IX to obtain: (Figure Remove) The tert-butoxycarbonyl protected aryl broir.ide 23 (4.0g, 9.5mmol), dry DMSO (25ml), NaH2P04 (454mg, 3.79mmol) and Na3HPO (1.62g, 11.4nunol) were combined and heated to 50°C under argon for approximately 3.5h. The mixture was then poured into water (200ml) and extracted with three lOOml portions of EtOAc. The combined organic layers were thoroughly washed with water, brine, dried over MgS04, filtered and concentrated to give a yellow solid which was purified by triturating with ethar.ol. to give 1.55g of a pale yellow solid (7). The mother liquor was purified by flash chromatography (10% EtOAc ir. hexane) to give an additior.al 454mq (60%). JH-NMR (CDC1,) d 1.77 (s, 9H) , 7.25 (s, 1H), 7.48 (m, 3H), 8.52 (m, 2H) 10.39 (s, 1H); m.p.» 156°C (dec). (Figure Remove) Aldehyde 7 (600mg, 1.7mmol) was dissolved in dry THF (20ml) and cooled to 0°C under argon. To this was added a 0°C solution of (tert-butoxycarbonylmethylene) -triphenylphosphorane (694mg, l.Smmol) in lOml of dry THF dropwise through a cannula. After 3h the mixture was concentrated and purified by triturating with ethanol to give 565mg (73%) of a white solid (8). 'HNMR (CDC13) d 1.58 (s, 9H), 1.79 (s, 9H), 6.46 (d, 1H). 6.95 (s, 1H), 7.48 (m, 3H), 8.09 (d, 1H), 8.56 im, 2H). (Figure Remove) A solution of compound 8 (565mg 1.2mmol) in 5ml THF was diluted to lOOml with EtOAc. After adding SOOmg of catalyst (5% wt Pd, 50% H:0) and purging with argon, the mixture was hydrogenated under atmospheric pressure. After 8h the mixture was filtered, concentrated and purified with flash chromatography (10% EtOAc in hexane) to isolate 200mg (35%) of 9 as a clear oii that crystallized upon standing. :HNMR (CDC1,) d 1.42 (s, 9H), 1.75 (s, 9H) , 2.65 (t, 2H), 3.32 (t, 2H) , 6.41 (s, 1H) 7.45 (m, 3H), 8 .51 (m, 2H) . (Figure Remove) Aryl chloride 9 (200mg, 0.44mmol), DMSO (lOml) and L-prolinamide (440mg, 4.4mmol) were combined and heated to 85°C under argon. After 14 hours the mixture is cooled to room temperature and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer washed with EtOAc (3x). The combined organic layers were thoroughly washed with water (3x), brine, dried over MgSO,, filtered and concentrated to give 10 as a yellow film which was purified by flash chromatography (2.5% MeOH in CH:C12) . 185mg (97%). MS (ES) : 435.8 (M' + l) . (Figure Remove) Ester 10 (30mg, înmoi) in 5ml dioxane was hydrolyzed by adding O.5ml concentrated HCI. After 3 hours the mixture was concentrated in vacuo and recrystalized in EtOH/ EtOAc to obtain 1509 as a white solid (20mg, 61%) . MS (ES): 380 (M*+l) . Example 26: Synthesis of [N-(2-phenyl-6-aminocarbonyl methoxymethyl-7tf-pyrrolo[2, 3-d] pyrimidin-4-yl) - (L) -prolinamide (1510) Compound 1510 was obtained using precursor compound 23 of synthesis scheme IX to obtain: (Figure Remove) Bromide 23 (1.27g, 3mmol) and molecular sieve (5g) are stirred in anhydrous methyl glycolate (5.8g, 60mmol) and DCM (40mL). The solution is treated with AgOTf under N, and allowed to ştir for 3h. The solid is removed by filtration and washed with DCM (2x20mL). The filtrate is concentrated : n vacuo. The residue is redissolved in DCM (80mL). The resulted sclution is then washed with water, saturated NaHC03 solution and brine, dried over MgSOt, filtered and concentrated to give 1.35g (99%) off white solid (12). 'H-NMR (CDC13) d 1.75 (s, 9H) , 3.80 (s, 3K) , 5.0 (s, 2H), 6.78 (s, 1H), 7.47 (m, 3H), 8.52 (m, 2H). (Figure Remove) Aryl chloride 12 (177mg, 0.41mmol), DMSO (lOmL), L-prolinamide (466mg, 4mmol) and NaHC03 (500mg) are combined and heated to 120°C under nitrogen. After 4h, the reaction is cooled to room temperature and diluted with water (60ml). The resulted slurry is extracted with DCM (5x30mL). The combined organic layers are washed with saturated NaHC03 solution and brine, dried over MgSO«, filtered and concentrated to give brown solid. Pure product (154mg, 92%) is obtained after flash column as white solid (13). 'H-NMR (CDC13) d 2.15 (m, 3H) , 2.52 (m, 1H) , 3.55 (s, 3H), 4.58 (s, 2H), 5.08 (s, 1H, ), 5.85 (brs, 1H), 6.48 (s, 1H), 7.08 (brs, 1H), 7.42 (m, 3H) , 8.40 (m, 2H), 10.58 (brs, 1H) ; MS (ES) : 410.1 (M'-t-l) .(Figure Remove) Methyl ester 13 (124mg, 0.3mmol) is dissoived in HOCH3 (15mL). Ammonia is bubbled through the solution for 0.5h. The reaction mixture is then stirred for another 3h at rt. After removal of solvent lllmg of a white solid (1510, .93%) is obtained. 'H-NMR (CDC13) d 1.82 (m, 3H) , 2.20 (m, 1H), 2.80 (m, 1K) , 3.10 (m, 1H), 3.63 (dd, 2H, Ji = 13.8Hz, J,=19.4Hz), 3.87 (m, 1H) , 4.07 (m, 1H), 4.97 (m, 1H), 5.96 (m, 2H) , 6.35 (s, 1H), 6.86 (brs, 1H), 7.11 (brs, 1H), 7.37 (m, 3H) , 8.28 (m, 2H), 11.46 (brs, 1H) ; MS (ES): 394.8 (M*+l). Example 27: Synthesis of [4- (2-Carbamoylpyrrolidin-l-yl)-2-phenyl-7#-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid] (1511) Compound 1511 was synthesized using precursor compound 15 of synthesis scheme VII to obtain: (Figure Remove) To a suspension of sodium hydride (780mg of a 60% oii suspension, 19.5rtunoi) in dry DMF (20mL), cooled by an ice/water bath, under nitrogen, is added a soluticn of the pyrrolopyrimidine 15 (2.00g, 7.52mmol) in DMF (IQmL) over 5 min. After 15 min, benzer.esulf onyl chloride (1.2inL, 9.40mmol) is added, then the cooling bath is removed. After 4h, the reaction mixture is poured into a mixture of ice and sat. NaHC03 sol., the precipitated solid is filtered of f and triturated with acetone (3 ) and methanol (2 ), yielding 2.37g of a beige solid. This solid (16) contains approx. 10mol-% DMF (based on that 83% yield) and can be used in the next step; a pure sample can be obtained by chromatography on silica gel using acetone as eluent. 1H-NMR (CDC13) : d 6.70 (d, J = 4.2Hz, 1H) , 7.47-7.63 (m, 6H), 7.76 (d, J= 4.2Hz, 1H), 8.24-8.32 (m, 2H) , 8.48-8.56 (m, 2H) ; IR (solid): n = 3146 cm'1, 1585, 1539, 1506, 1450, 1417, 1386, 1370, 1186, 1176, 1154, 1111, 1015, 919, 726, 683, 616, 607; MS (ES): 372/370 (MH*J; mp = 226-227 °C. (Figure Remove) To a solution of the W-sulfonyl compound 16 (337mg, 0.911mmol) in dry THF (34mL), cooled by dry ice/acetone, is added LDA'THF (l.OmL, l.5M solution in cyclohexane, l.5mmol). After 45min, carbon dioxide is bubbled into the solution for 5min, then the cooling bath is removed. When the solution has reached ambient temp., the solvents are evaporated, yielding 398rag of the salt 17, containing 0.5 equiv. of (iPr) 2NCO:Li, as yeilow solid. The salt is used without purificaticn in the next step. '"H-NMR (D6-DMSO) : d = 6.44 (s, 1H), 7.50-7.75 (m, 6H), 8.33-8.40 (m, 2H) , 8.53 (dd, J - 8.0, l.SHz, 2H). (Figure Remove) A solution of the lithium salt 17 (50mg) and L-prolinamide (122mg, 1.07mmol) in DMSO (l.5mL) is heated under nitrogen to 80 °C for 15.5h. 4% aq. acetic acid (lOmL) is added to the cooled solution, and the mixture is extracted with EtOAc (5'lOmL). The combined organic layers are washed with 4% aq. acetic acid (lOmL), water (lOmL) and brine (lOmL) and are dried over MgS04. Filtration and concentration gives 40mg of 18 as a yellowish solid, which is used without purification in the next step. XH-NMR (CD3OD) : d - 1.95-2.36 (m, 4H) , 3.85-3.95 (m, 1H), 3.95-4.17 (m, 1H), 4.72 (brs, 1H), 7.14 (s, 1H), 7.35-7.45 (m, 3H), 7.45-7.70 (m, 3H), 8.33-8.50 (m, 4H). (Figure Remove) A solution of sodium hydroxide in methanol (l.SmL, 5M, 7.5nunol) is added to a solution of the pyrroiopyrimicine 18 (40mg, 0.081mmol) in methanol (2mL). After 2h, the pH is adjusted to 5, most of the methanol is evaporated, the mixture is extracted with EtOAc (5 lOmL), the combined organic layers are washed with brine and dried over MgSO«. Filtration and concentration yields 24mg of a pale yellow solid, which is triturated with toluene/EtOAc/MeOH to yield 15.6mg (55%) of the acid 1511 as slightly yeliowish solid. 'H-NMR (CD3OD) : d = 2.05-2.20 (m, 4H), 3.95-4.10 (m, 1H), 4.15-4.25 (m, 1H), 4.85 (brs, 1H) , 7.14 (s, 1H) , 7.35-7.42 (m, 3H), 8.38-8.45 (m, 2H); IR (solid): n = 3192 cm'1, 2964, 2923, 2877, 1682, 1614, 1567, 1531, 1454, 1374, 1352, 1295, 1262, 1190, 974, 754, 700; MS (ES): 352 (M'+l); m.p. = 220 °C (decomp.). Example 28: Synthesis of l- (6-methyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-4-yl)-(S)-pyrrolidine-2 -carboxylic acid amide (1512) Compound 1512 was synthesized by the following steps: (Figure Remove) Aryl chloride 20 (3g, 10.7 mmol), DMSO (50ml) and (S)-prolinamide were combined and heated to 85°C under argon. After stirring overnight (14hrs), the mixture was cooled to room temperatura and poured into SOOml of wacer. This was extracted with three 200ml portions of EtOAc. The combinec organic layers were thoroughly washed with water (3 x 300 ml) , brine, dried over MgS04, filtered and concentrated to give a dark brown solid. The solid was recrystallized twice from EtOAc to yield 1.95g (57%) of a tan solid (1512). :HNMR (DMSO-dJ d 1.8-2.2 (m, 4H), 2.3 (s, 3H), 3.8 (m, 1H), 4.0 (m, 1H) , 4.6 (d, 1H) 6.2 (s, 1H), 6.9 (s, 1H), 7.2 (m, 3H), 7.3 (s, 1H), 8.4 (m, 2H) , 11.5 (s, 1H); MS (ES) : 322 (M*+l) Example 29: Synthesis of l-[6-(2-Hydroxy-ethoxymethyl) -2-phenyl-7H-pyrrolo [2, 3-d] pyriraidin-4-yl] -pyrrolidine-2-carb oxylic acid amide(1513) Compound 1513 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with L-prolineamide and ethane-1,2-diol to obtain: (igure Remove) Example 30: Synthesis of 4-(6-Imidazol-l-ylmethyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-cyclohexanol (1514) . Compound 1514 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with N-6 amino cyclohexanol and imidazole to obtain: (Figure Remove) (Figure Remove) MS (ES): 389 (M'+l) Example 31: Synthesis of 4-(4-Hydroxy-cyclohexylamino) -2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (1515) Compound 1515 was synthesized in a manner similar to that of Example 27 using synthesis scheme i IX with N-6 amino cyclohexanol to obtain: (Figure Remove) Example 32: Synthesis of 4-[6-(2-Hydroxy-ethoxymethyl} -2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino]-cyclohexanol (1516) Compound 1516 was synthesized in a manner similar to that of Compound 1513 using synthesis scheme IX with N-6 amino cyclohexanol to obtain: (Figure Remove) Example 33: Synthesis of 4-(4-Hydroxy-cyclohexylamino) -2-phenyl-lH-pyrrolo[2, 3-d]pyrimidine-6-carboxylic acid methyl ester (1517) (Figure Remove) A solution of the lithiura salt 17 (O.ISmmol) in dry DMF (4mL) îs stirred with methyl iodide (O.lmL, 1.6mmol) at 20 °C under argon for 3h. DMF is evaporated, and aqueous anunonium chloride solution is added (15mL). The mixture is extracted with EtOAc (3'15mL), the combined organic layers are washed with water (2'lOmL) and brine (lOmL) and are dried over MgSO«. Filtration and concentration gives 21mg (38%) of the methyl ester 22. (Figure Remove) A solution cf the merhyl ester 22 (24.5mg, 0.057mmol) and 4-trans-aminocyclohexanol (66mg, 0.57mmol) in DMSO (1.5mL) is heated under nitrogen to 80 °C for 5h, then the heating is stopped, and stirring at 20 °C is continued for 13.5h. 4% aq. acetic acid (lOmL) is added to the cooled soluticn, and the mixture is extracted with EtOAc (3'10mL). The combined organic layers are washed with 4% aq. acetic acid (lOmL), water (lOmL) 2N NaOH (lOmL), water (lOmL), and brine (lOmL) and are dried over MgSO<. to a solution of the crude material obtained af ter> filtration and concentration (1H NMR indicates about 50% removal of the benzenesulfonyl group) in THF (2mL) is added a solution of NaOH in MeOH (O.SmL of 5w solution, 2.5mmol) at ambient temperature. After 20min, water and sat. NaHC03 sclution (5mL each) are added, and the mixture is extracted with EtOAc (4"15mL). The combined organic layers are washed with 2N NaOH (lOmL), water (lOmL), and brine (lOmL) and are dried over MgS04. Chromatography of the crude material obtained after filtration and concentration on silica gel, eluting with hexanes/EtOAc 1:1 ® 1:2 yields 8.6mg (41%) of 1517 as a white solid, mp. 225-227 °C. 'H-NMR (CD3OD) : d = 1.38-1.62 (m, 4H), 1.95-2.10 (m, 2H), 2.10-2.25 (m, 2H), 3.55-3.70 (m, 1H), 3.91 (s, 3H), 4.20-4.35 (m, 1H) , 7.32 (s, 1H), 7.35-7.47 (m, 3H) , 8.35-8.42 (m, 2H) ; IR (solid): n - 3352 cm'1, 3064, 2935, 2860, 1701, 1605, 1588, 1574, 1534, 1447, 1386, 1333, 1263, 1206, 1164, 1074, 938, 756, 705; MS (ES): 367 (MH*). Example 34: Synthesis of [4- (2-Carbamoyl-pyrrolidin-l-yl) -2-phenyi-7H-pyrrolo [2, 3-d]pyrimicin-6-ylmethoxy] -acetic acid methyl ester (1518) Compound 1518 was synthesized in a manner similar to example 26 using precursor compound 12 to obtain: (Figure Remove) Eample 35: Synthesis of [4-(2-Carbamoyl-pyrrolidin-l-yl) -2-phenyl-7H-pyrrolo [2, 3-d] pyrimidin-6-ylmethoxy] -acetic acid (1519) Compound 1519 was synthesized in a manner similar to compound 1518 wherein the methyl ester group was hydrolized with a base to obtain: (Figure Remove) MS (ES): 396 (M*+l) Example 40: Synthesis of 4-(4-Hydroxy-cyclohexylamino) -2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid amide (1520) (Figure Remove) Gaseous ammonia is condensed into a solution of the pyrrolopyrimicine 23 (7.8mc, 0.02lmmol) in methanol (6mL), cooled by dry ice/acetone, until a total volume of 12mL is reached. After stirring for lOd at 20 °C, the solventa are evaporated, and the residue is purified by preparative TLC on silica gel, eluting with 5% MeOH in CH,C12. The material thus obtained is triturated with ether to yield 6. 5rng (88%) of the anide 1520 as white solid, mp. 210-220 °C (decomp.). :H-NMR (CD3OD) : d = l .40-1.60 (m, 4H) , 2.00-2.15 (m, 2H) , 2.15-2.25 (m, 2H), 3.55-3.70 (m, 1H) , 4.20-4.35 (ir., 1H) , 7.16 (s, 1H), 7.35-7.47 (m, 3H) , 8.34-8.40 (m, 2H) ; IR (solid): n = 3358 cm'1, 3064, 3025, 2964, 2924, 2853, 1652, 1593, 1539, 1493, 1452, 1374, 1326, 1251, 1197, 1113, 1074, 1028, 751, 699; MS (ES): 352 (MJT) . Ac'ivitv of Compounds Adenosine l (Aa) receptor subtype saturation and competition radio ligand binding were carried out for compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, and 1520 as described herein and inter alia, on pages 152-153 of this specification. AII of the above-referenced compounds equaled or surpassed the Aj receptor binding affinity of reference compounds 1318 or 1319 as described herein and, inter alia, in Table 13, on page 171 of the specification. The water solubilities of the above compounds listed in Table 1319 due to their cLogP values, which were calculated using the computer program CS ChemDraw, ChemDraw Ultra ver. 6.0 ©1999 as provided by CambridgeSoft Corporation, 100 Cambridge Park Drive, Cambridge, MĂ 02140. The compounds specific to the A, receptor listed in Table 18 hâd lower cLogP values, between about l.5 to about 3.4, as compared to reference compounds 1318 or 1319 with a cLogP value about 3.8. It was not predicted that the more polar Aj receptor compounds listed in Table 18 having lower cLogP values than the reference compounds 1318 or 1319 would still retain the potency and A! receptor binding selectivity as compared to those reference compounds. (Table Removed) Paaes 288-293 reiate to additional compounds specific to A-. receptor This invention provides a compound having the structura: (Figure Removed) This invention also provides a compound having the structure: (Figure Removed) In a further embodiment the invention provides a method for treating a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject are therapeutically effeccive amount of compounds 1609 or 1610. The invention also provides the' above method, wherein the subject is a mammal. The invention further provides the above method, wherein the mammal is a human. The invention also provides the method for treating a disease associated with A2a adenosine receptor in a subject, wherein the A2a adenosine receptor is associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, senile dementia, or Parkinson's disease. The invention provides the above method, wherein the compound treats the diseases by stimulating adenylate cyclase. The invention also provides a water-soluble prodrug of the compound 1609 or 1610, wherein the water-soluble prodrug is metabolized in vivo to an active drug to selectively inhibit an A2a adenosine receptor. The invention also provides a water-soluble prodrug of the compound 1609 or 1610, wherein the prodrug is metabolized in vivo by esterase catalyzed hydrolysis. The invention also provides a pharmaceutical composition comprising the water-soluble prodrug of the compound 1609 or 1610, and a pharmaceutically acceptable carrier. The invention also provides a msthod for inhibiting the activity of an A2â adenosine receptor in a cell, which comprises contacting the cell with compound 1603 or 1610. The invention also provides a method for inhibiting the activity of an A2â adenosine receptor in a cell, which comprises contacting the cell with compound 1609 or 1610, wherein the compound is an antagonist of said A2a adenosine receptor. The invention also provides the above method, wherein the cell is a human cell. The invention also provides the above method, wherein the cell is a human cell and the compound is an antagonist of A2a adenosine receptors. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1609 or 1610 and a pharmaceutically acceptable carrier. The invention also provides the above pharmaceutical composition, wherein the therapeutically effective amount is effective to treat Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is an ophthalmic formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is a systemic formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is a. surgical irrigating solution. The invention also provides a combination therapy for Parkinson's disease, comprising the compounds 1609 or 1610, and any of the dopamine enhancers. The invention also provides a combination therapy for cancer, comprising the compound 1609 or 1610, and any of the cytotoxic agents. The invention also provides a combination therapy for glaucoma, comprising the compound 1609 or 1610, and a prostaglandin agonist, a muscrinic agonist, or a P-2 antagonist. The invention also provides a packaged pharmaceutical composition for treating a disease associated with A2a adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound 1609 or 1610; and(b) instructions for using the compound for treating said disease in a subjecc. Exemplification Exampl* 41: Synthesis of l- (6-Phenyl-2-pyridin-4-yl- 7H-pyrrolo[2,3-d]pyrimidin- Compound 1609 was synthesized by reacting L-proiinamide with the appropriate chloride intermediate described in synthesis scheme II on page 82 to obtain: (Figure Removed) 'H-NMR (d6-DMSO) d 1.95-2.15 (m, 4H) , 4.00 (brs, 1H) , 4.15 (brs, 1H), 4.72 (brs, 1H) , 6.90 (brs, 1H), 7.19 (brs, 1H), 7.30 (t, 1H, J - 7.0Hz), 7.44 (t, 2H, J = 7.0Hz), 7.59 (s, 1H), 7.92 (brs, 2H), 8.26 (d,2H, J = 6.2Hz), 8.65 (d, 2H, J = 6.2Hz); MS (ES) : 384.9 (M' + l); Mpt = 280-316°C (decomp.). Examplc 42: Synthesis of l-[6-(3-Methoxy-phenyl)-2-pyridin-4-yl-7tf-pyrrolo[2, 3-d] pyrimidin-4-yl] -pyrrolidine-2-carboxylic acid amide (1610). Compound 1610 was synthesized by reacting L-prolinamide with the appropriate chloride intermediate described in synrhesis scheme II on page 82 to obtain: (Figure Removed) d 2.07(m,4H), 3.85(s,3H), 4.02(m,lH), 4.17(m,lH], 4.75(m,lH), 6.89(m,lH), 7.00{s,lH), 7.23(s,lH), 7.35(t,lH,J=8.2Hz), 7.53(s,2H), 7.60(s,lH), 8.28(d,2H,J=5.8Hz), 8.67(d,2H,J=5.8Hz), 12.37(s,1H); MS (ES): 415.0 (MT+1). Activitv of Compounds Adenosine 2a (A2J receptor subtype competition radio ligand binding were carried out for compounds 1609 and 1610 as described herein and inter alia, on page 153 of this specif ication. Compounds 1609 and 1610 were found have A2a receptor binding affinity and selectivity.Pages 294-300 relata t-n addicinnal coinpounds specific tn A. receptor This invention also provides a compound having the structura: (Figure Removed) In a furrher embodiment the invention provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting the cell with the compound 1720. In a further embodiment the invention provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the compound is an antagonist of the A3 adenosine receptor. In a further embodiment the invention provides the above method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the cell is human cell. In a further embodiment the invention provides the above method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the cell is a human cell and wherein the compound is an antagonist of AJ adenosine receptors. In a further embodiment the invention provides a method of treating damage to the eye of a subject which comprises administering to the subject a composition comprising a therapeutically effective amount of the compound 1720. In a further embodiment the invention provides the above method, wherein the damage comprises retinal or optic nerve head damage. In a further embodiment the invention prcvides a therapy for glaucoma, comprising administering to a subject a therapeutically effective amount of the compound 1720. In a further embodiment the invention provides a therapy for glaucoma comprising one or more adenosine receptor antagonists, preferably comprising an adenosine receptor A3 antagonist (preferably an N-6 substituted 7-deazapurine, most preferably [2-(3#-Imidazol-4-yl)-ethyl]-(2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine). In an alternative embodiment the invention provides a combination therapy for glaucoma comprising an adenosine receptor A3 antagonist (preferably an N-6 substituted 7-deazapurine, most preferably [2-(3H-Imidazol-4-yl)-ethyl]-(2-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine)) and one or more other compounds selected from the group consisting of beta adrenoceptor antagonists (i.e. beta adrenergic antagonists or b-blockers) (e.g. timolol maleace, becaxolci, carteolol, levcbunolol, metipranolol, L-653328 (the acetate ester of L-652698), beta l adrenoceptor antagonists}, alpha-2 adrenoceptoragonists (e.g. aplaclonidine, brimonidine, AGN-195795, AGN-190837 (an analog of Bay-a-6781)) , carbonic anhydrase nhibitors (brinzolamide, dorzolamide, MK-927 (an inhibitor of te human carbonic anhydrase II isoenzyme), inhibitors of arbonic anhydrase IV isoenzyme), cholinergic agonists (e.g. mcuscarinic cholinergic agonists, carbachol, pilocarpine HC1, pilocarpine nitrate, pilocarpine, pilocarpine prodrugs (e.g. DD-22A)), prostaglandins and prostaglandin receptor agonists (e.g. latanoprost, unoprostone isopropyl, PGF2 alpha agonists, prostanoid-selective FP receptor agonists, PG agonists such as the hypotensive prostamides) , angiotensin converting enzyme (ACE) inhibitors (e.g. Spirapril, spiraprilat) , AMPA receptor antagonists, 5-HT agonists (e.g. a selective 5-HT IA receptor agonist such as MKC-242 (5-3-[ ( (25)-l,4-benzodioxan-2- ylmethyl)amino]propoxy-1,3-benxodioxole HCl), angiogenesis inhibitors (e.g. the steroid anecortave), NMDA antagonists (e.g. HU-211, memantine, the cannabinoid NMDA-receptor agonist dexanabinol, prodrugs and analogs of dexanabinol, NR2B- selective antagonists (e.g. eliprodil (SL-82.0715)), renin inhibitors (e.g. CGP-38560, SR-43845), cannabinoid receptor agonists (e.g. tetrahydrocannabinol (THC) and THC analogs, selective CB2 cannabinoid receptor agonists (e.g. L-768242, L- 759787), compounds such as anandamide that bind to both brain- specific CB1 receptors and peripheral CB2 receptors), angiotensin receptor antagonists (e.g., angiotensin II receptor antagonists (e.g. CS-088), selective angiotensin II AT-I eceptor antagonists, such as losartan potassium), hydrochlorothiaziae (HCT2), somatostatin agonists (e.g. the non-peptide somatostatin agonist NNC-26-S100), glucocorticoid antagonists, mast cell degranulation inhibitors (e.g. nedocromil), alpha-adrenergic receptor blockers (e.g. dapiprazole, alpha-2 adrenoceptor antagonista, alpha l adrenoceptor antagonists (e.g. bunazosin)), alpha-2 adrenoceptor antagonists, thromboxane A2 mimetics, protein kinase inhibitors (e.g. H7), prostaglandin F derivatives (e.g. S-1033), prostaglandin-2 alpha antagonists (e.g. PhXA-34), dopamine Dl and 5-HT2 agonists (fenoldopam), nitric-oxide- releasing agents (e.g. NCX-904 or NCX-905, nitric-oxide- releasing derivatives of timolol), 5-HT 2 antagonists (e.g. sarpogrelate), NMDA antagonists (e.g. prodrugs and analogs of dexanabinol), alpha l adrenoceptor antagonists (e.g. bunazosin), cyclooxygenase inhibitors (e.g. diclofenac, or the non-steroidal compound nepafenac), inosine, dopamine D2 receptor and alpha 2 adrenoceptor agonists (e.g. talipexole), dopamine Dl receptor antagonist and D2 receptor agonists (e.g. SDZ-GLC-756), vasopressin receptor antagonists (e.g. vasopressin V2 receptor antagonists (e.g. SR-121463)), endothelin antagonists (e.g. TBC-2576) , l-(3-hydroxy-2- phosphonylmethoxypropyi; cytosine (HPMPC) and related analogs and prodrugs, thyroid hormone receptor ligands (e.g. KB- 130015), muscarinic Ml agonists, NMDA-receptor antagonists (e.g. the cannabinoid NMDA-receptor antagonist dexanabinol), PG agonists such as the hypotensive lipids, prostamides, sodium channel blockers, NMDA antagonists, raixed-actior. ion channel blockers, beta adrenoceptor antagonist and PGF2 alpha agonist combinations (e.g. latanoprost and timolol), guanylate cyclase activators (e.g. atrial natriuretic peptide (ANP) or non-peptide mimetics, inhibitors of AN? neutral endopeptidase, nitrovasodilators (e.g. nitroglycerin, hydralazine, sodium nitroprusside) ,.. endothelin receptor modulatcrs (e.g. ET-1 or non-peptide mimetics, sarafctoxin-S6c), ethacrynic acid, other phenoxyacetic acid analogs (e.g. indacrinone, ticrynafen), actin disrupters (e.g. latrunculin), calcium channel blockers (e.g. verapamil, nifedipine, brovincamine, nivaldipine) and neuroprotective agents. A combination therapy for glaucoma, comprising the compound of 1702, and one or more compounds selected f rom the group consisting of beta adrenoceptor antagonists, alpha-2 adrenoceptor agonists, carbonic anhydrase inhibitors, cholinergic agonists and prostaglandin receptor agonists. In a further embodiment the invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1720 and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a packaged pharmaceutical composition for treating a disease associated with A3 adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound 1720; and (b) instructions for using said compound for treating said disease in a subject. In a further embodiment the invention provides a method of making a coraposition which comprises the compound 1720, the method comprising admixing the compound 1702 with a suitable carrier. In a further embodiment the invention provides a pharmaceutically acceptable salt of compound 1720, wherein the pharmaceutically acceptable salt contains an anion selected f rom the group consisting of maleic, fumărie, tartaric, acetate, phosphate and mesylate. Exemplification Exanple 43: Synthesis of [2-(3#-Imidazol-4-yl)-ethyl]-(2- phenyl-7tf-pyrrolo[2,3-djpyrimidin-4-yl)-amine (1720) Compound 1720 was synthesized using precursor compound l of synthesis scheme VII to obtain: (Figure Removed) Aryl chloride l (400mg, l.SOmmol), DMSO (1.67g, IS.Ommol) are combined and heated to 120°C under nitrogen. After .5h,the reaction is cooled to room temperatura and partitioned between EtOAc and water. The layers are separated and the aqueous layer is extracted with EtOAc (3x). The combined organic layers are washed with brine (2x) , dried over MgSO„, filtered and concentrated to yield 494mg of a brown solid. The solid is washed with cold MeOH and recrystallized from MeOH to yield lS7mg (43%) of an off white solid (1720). 'H-NMR (CD3OD) d 3. 05 (t, 2H, J = 7.0Hz), 3.94 (t, 2H, J = 7.0HZ), 6.50 (d, 1H, J = 3.5Hz), 6.88 (brs, 1H) , 7.04 (d, 1H, J - 3.5Hz), 7.42 (m, 3H) , 7.57 (s, 1H), 8.34 (m, 2H) ; MS (ES) : 305.1 (M'+l); Mpt = 234-235°C. Activitv of Compounds Adenosine 3 (A3) receptor competition radio ligand binding was carried out for compound 1720 as described herein and inter alia, on pages 153-154 of this specification. Compound 1720 was found to nave an A3 receptor binding affinity greater than 10 times that of reference compound 1308 as described herein and, inter alia, in Table 13, on page 169 of the specification. Incorporation by Reference AII patents, published patent applications and ottier references cisclosed herein are hereby expressiy .incorporated harein by reference. Equivalents Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, many equivalents to specific embodiments of the invention described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims. WE CLAIM: 1. A N-6 substituted 7-deazapurine, having the structure: (Structure Removed) wherein N, Rx and R2 together form (Formula Removed) wherein m is 0, 1, 2, or 3; RA and RB are each independently be H, -OH, -CH2OH, -CH2CH2OH, -C(=O)NH2, a heteroatom, or -C(=O)NR11R11' ; wherein R11 is aryl, substituted aryl, or heteroaryl; wherein R11' is alkyl, or XRn", wherein X is 0, or N and R11" is substituted alkyl or aryl; wherein R3 is a substituted or unsubstituted four to six membered ring; wherein R5, is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R7) (R8)XRq, wherein X is 0, S, or NR10, wherein R7 and R8 are each independently H or alkyl, wherein Rg and R10 are each independently alkyl or cycloalkyl, or R9, R10 and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members; wherein R6 is H, alkyl, substituted alkyl, or cycloalkyl, wherein when NRxR2 is wherein R is RA or RB. Y is 0, S, or NR, 2. A N-6 substituted 7-deazapurine as claimed in claim 1, having the structure: (Formula Removed) wherein m is 0, 1, 2, or 3; wherein RA and RB are each independently be H, -OH, -CH20H, -CH2CH2OH, -C(=O)NH2, a neteroatom, or -C(=O) NRnRn' ; wherein R11 is aryl, substituted aryl, or heteroaryl; wherein R11' is alkyl, or XR21", wherein X is O, or N and Rn" is substituted alkyl cr a r y 1 . 3. A N-6 substituted 7-deazapurine as claimed in claim 1, having the structure: (Structure Removed) wherein m is 0, 1, 2, or 3; wherein Y is 0, S, or NR; wherein R is RA or RB; wherein RA and RB are each independently be H, -OH, -CH2OH, -CH2CH2OH, -C(=O)NH2, a heteroatom, or -C (=O) NRnRn'; wherein R11 is aryl, substituted aryl, or heteroaryl; wherein R11' is alkyl, or XR11", wherein X is 0, or N and R11" is substituted alkyl or aryl.

Documents:

in-pct-2002-00621-abstract.pdf

IN-PCT-2002-00621-DEL-Abstract-(12-12-2008).pdf

IN-PCT-2002-00621-DEL-Assignment-(23-12-2008).pdf

IN-PCT-2002-00621-DEL-Claims-(12-12-2008).pdf

IN-PCT-2002-00621-DEL-Claims-(23-12-2008).pdf

in-pct-2002-00621-del-claims.pdf

IN-PCT-2002-00621-DEL-Correspondence-Others-(12-12-2008).pdf

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in-pct-2002-00621-del-correspondence-others.pdf

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IN-PCT-2002-00621-DEL-Form-1-(12-12-2008).pdf

in-pct-2002-00621-del-form-1.pdf

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IN-PCT-2002-00621-DEL-Form-2-(12-12-2008).pdf

in-pct-2002-00621-del-form-2.pdf

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in-pct-2002-00621-del-form-3.pdf

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IN-PCT-2002-00621-DEL-GPA-(23-12-2008).pdf

in-pct-2002-00621-del-pct-101.pdf

in-pct-2002-00621-del-pct-210.pdf

in-pct-2002-00621-del-pct-401.pdf

in-pct-2002-00621-del-pct-409.pdf

in-pct-2002-00621-del-pct-416.pdf

IN-PCT-2002-00621-DEL-Petition-137-(12-12-2008).pdf

IN-PCT-2002-00621-DEL-Petition-137-(23-12-2008).pdf

IN-PCT-2002-00621-DEL-Petition-138-(12-12-2008).pdf