Title of Invention	2-SUBSTITUTED PHENYL-5,7-DIHYDROCARBYL-3,7-DIHYDROPYRROLO [2,3-d] PYRIMIDIN-4-ONE DERIVATIVES, AND A METHOD OF PREPARATION THEREOF
Abstract	The invention relates to the compounds of formula 1, their preparation and the pharmaceutical compositions containing the compounds. The invention also relates to the use of the compounds of formula I in preparing medicines, which can treat sexual dysfunction of animals including human (male and female), especially erectile dysfunction of male and the diseases in which the function of phospholipase 5 (cGMP PDE5) is involved.

Title of Invention

2-SUBSTITUTED PHENYL-5,7-DIHYDROCARBYL-3,7-DIHYDROPYRROLO [2,3-d] PYRIMIDIN-4-ONE DERIVATIVES, AND A METHOD OF PREPARATION THEREOF

Abstract

The invention relates to the compounds of formula 1, their preparation and the pharmaceutical compositions containing the compounds. The invention also relates to the use of the compounds of formula I in preparing medicines, which can treat sexual dysfunction of animals including human (male and female), especially erectile dysfunction of male and the diseases in which the function of phospholipase 5 (cGMP PDE5) is involved.

Full Text	2-substituted phenyl-5, 7-dihydrocarbyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one derivatives, the preparation and the pharmaceutical use thereof Field of invention The present invention relates to 2-substituted phenyl-5,7-dihydrocarbyl-3/7-dihydropyrrolo[ 2,3-d]pyrim idin-4-one derivatives, the process for their preparation, the composition containing them, and the use for treatment and/or prevention of sexual dysfunction and other diseases related to phospholipase 5. Background of invention Sildenafil, disclosed in WO942 8 902, is first kind of orally-administrated potent inhibitors of phospholipase 5 in treatment of the erectile dysfunction of man. By inhibiting the phospholipase 5 in corpus cavernosum, it can achieve the purpose of relaxing smooth muscle in human corpus cavernosum, improving penile hyperemia so as to result in erection. The effective rates of sildenafil in treating male sexual organs erectile dysfunction amount to 30%. Also, Pfizer Ltd. has developed a series of 1,6-dihydropyrrol [4,3-d] pyrimidin-7-one derivatives, and broadened their therapeutic area where such indi cat ions was thought to be treated by inhibiting phospholipase 5. All of these compounds are disclosed in EP0951098, WO9849116, US6251904, and WO0024745, and the latter two of patents include the compounds whose substituted phenyl on C-5 is replaced by the substituted pyridin-2-yl. On the basis of the structure of Sildenafil, DONG A PHARMA Co . Ltd. of Korea developed a series of mono substituted derivatives in the nitrogen atom of sulfonylamino group, as disclosed in WO0027848 and WO0198304. Presently, as described in WO0216364, in order to further enhance water-solubility, LG Chem . Invest. Ltd. disclosed the derivatJ ves of 1,6-dihydropyrrolo[4,3-d]-pyrimidin-7-one with polyethylene glycol. In addition, 1,5-dihydropyrrolo[3,4-d]pyrimidin-4-ones and 1,9-dihydropurin-6~ones were developed by Pfizer Ltd. for the treatment of sexual dysfunction(US6100270) . WO016082b disclosed 3,5-dihydropyrrolo[3,2-d]pyrimidin-4-ones are useful for the treatment of impotence. Recently, 3H-imidazo[5,1-f][1,2,4]triazin-4-ones was disclosed by Bayer Co. Ltd. in the patent application DE19881732. Detailed description of the invention The object of the present invention is to provide compounds for treatment of sexual dysfunction and other diseases related to phospholipase 5. Thus, according to one aspect, the invention provides novel aryl substituted 3,7-dihydropyrrolo[2,3-d] pyrimidin-4-ones and their pharmaceutically acceptable salts (also named Yonkenaf il) , the compounds are the structure of general formula ( I ) : I wherein R1 is H; Ci~C4 branched or straight chain alkyl; Ci~C,i halogenated branched or straight chain alkyl; C;^CG alkenyl; C2-C4 alkynyl; pyridyl, pyrimidinyl,imidazolyl; except H, the above substituents may be optionally substituted with one or more following groups: halogen, cyano, nitro, hydroxyl, carboxyl, guanidino, Ci~C4 alkyl, C.i~C4 alkoxyl, C1-C4 alkanoyl, C-^C^ cycloalkyl, substituted phenyl, substituted heterocyclic group, CONR5R6, NR'R^', COR7, NHSO9R8 or SO2NR9R10; R^ is H; Ci^Cs branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyi; C?-C{, aikenyl ; C-^Ca alkynyl; substituted phenyl; except. H, the above substituents may be optionally substituted w.i th one or more following groups: halogen, cyano-, nitro, hydroxy], carboxyl, guanidino-, Cj -C4 alkyl, Ci -C/j alkoxyl, Cj -Cr{ alkanoyl, C3-C5 cycloalkyl, substituted heterocyclic group, CONR6R7, NR6R7, C0?R8, NHSO2RH or SO2NRl0Rn; R3 is H; Cj-Ce branched or straight chain alkyl which may be optionally substituted with C3-C6 cycloalkyl or C1-C4 alkoxyl; C2-C4 alkenyl; C2-C4 alkynyl; R is H; C1-C6branched or straight chain alkyl which may be optionally substituted with C3-C6 cycloalkyl or Ci^C4 alkoxyl; C2~C4 alkenyl; C2^C4 alkynyl; R~ is H; C1-C4 branched or straight chain alkyl which may be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO2R8 ; C2^C4 alkenyl which may be optionally substituted with CN,CONR6R7 or CO2R8; C2-C4 alkoxyl optionally substituted with NR6Ry; (C2~C3 alkoxyl) C1-C2 branched or straight chain alkyl optionally substituted with OH or NR6R7; CONR6R7; CO,RB; halogen; NR6R7; NHSO2NR6R7; NHSO2R5; SO2NRi0Rjl; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, thienyl, or triazolyl, either of which is optionally substituted with methyl; R6 and R7 are each independently H or C1/-C4 branched or straight chain alkyl; or R6 and R' together with their attached nitrogen atom form pyrrolinyl, piper idyl , morpholinyl, 4-N(R12)-piperazinyl or imidazolyl, either of which is optionally substituted with methyl or hydroxyl; R8 is H; Cj-Cfs branched or straight chain alkyl optionally substituted with C]~C4 alkoxyl, C1-C4 alkylamino, dialkylamino; substituted phenyl and substituted heterocyclic group in which the substitut(s) on the ring of substituted phenyl and substituted heterocyclic group are defined as the above; R9 is C1-C3 alkyl optionally substituted with NR6R7; R10 and R11 are each independently H or C1/-C12 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C?-C6 alkenyl; C2~-C6 alkynyl or C-^Ce cycloalkyl; or R10 and R11take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholi nyl, 4-N (R13)-piperazinyl; or R10 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholi nyl, or 4-N (R1") -piperazinyl; the said groups are optionally substituted with OH, CN, CO2R(i, Cj-CU branched or straight chain alkyl, Cj^C^ alkoxyl, NR14Rjl or CONR14Ri5; substituted phenyl, substituted heterocyclic group, or Cx-C6 branched or straight chain aikyJ. substituted with substituted phenyl or substituted heterocyclic group, the said groups are optionally further substituted with OH, CO2R8, NR14R15, CONR14Rllj, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group; R1' is H; Ci-C6 branched or straight chain alkyl which may be optionally substituted with phenyl, C-'-C-] a 1 ky 1 substituted by hydroxyl, or Ci -C4 a.l koxyl; Ci -C3 fluoroa 1 ky 1 ; Co-Ce alkenyi; C2^C6 alkynyi; or C^C^ cycloalkyl; R! Ms H; Ci-C6 branched or straight chain alkyl; C?-C6 branched or straight chain alkyl substituted with C[~C-$ alkoxyl; C:'-Ctl branched or straight chain alkyl substituted with hydroxy.1 ; C2^C6 branched or straight chain alkyl substituted with NR14Rirr); C2^CG branched or straight chain alkyl substituted with phenyl; Ci^-C^ branched or straight chain aikyl substituted with CONR14R15; Co-C^branched or straight chain hydrocarbyl substituted with CO2RB; C2~C6 branched or straight chain hydrocarbyl having substituted phenyl or substituted heterocyclic group as substituent; COoR8, CONR^R15, CSNR14R1S or C (NH) NRi4Rlb; Ci-C3 halogenated branched or straight chain alkyl; C:.-C6 alkenyl; CS^Cf, alkynyl or C3~Ce cylcloalkyl; or polyethylene glycol group (n=2~20), which is optionally substituted with Cj-~C6 aikyl on its terminal; R]4 and R15 are each independently H; Ci~C4 branched or straight chain alkyl; C2~C4 branched or straight chain alkyl substituted with C1-C3 alkoxyl; or C2~-C4 branched or straight. chain alkyl substituted with hydroxyl; or Ri1 and Rin together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl; and the substituted phenyl refers to a phenyJ which is substituted with one or more groups selected from Cj~C] alkoxyl, halogen, cyano-, CF3, OCF'3, C1-C4 branched or straight chain alkyl on the phenyl ring; The substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxides thereof; pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituting groups on the heterocyclic ring are C-I-C well as C1-C4 branched or straight chain alkyl amino, C1-C4 alkoxylamino group. In another aspect, the invention provides processes for preparation of compounds of the formula I and intermediates used in the preparation thereof. The process for preparation of compounds of the general formula I comprises: The compounds of formula IE with a compound of formula IF wherein R , Rz, R , R and R~ are defined as previous, are reacted in an inert solvent such as dichloromethane and toluene and the like to produce the compounds of formula ID, ID Wherein R1, R2, R3, R4 and Rb are defined as previous. This reaction is carried out in the presence of an organic base such as tertiary amine, pyridine as a catalyst as well as an acid neutralizer at -20°C to 80°C. And then compounds of formula IA may be obtained by heating compounds of formula ID in an acidic aqueous solution, generally phosphoric acid aqueous solution: Wherein R1, R4-, R3, R4 and R5 are as previously defined. And then the compounds of formula I is obtained by a cyclization reaction of compounds of formula IA : Wherein R1, R2, R3, R4 and Rs are defined as previous. The cyclization reaction is similar to a convent: i ona.l method known for synthesis of pyrimidone. The reaction may be carried out by reflux in an appropriate solution under acidic, basic or neutral condition. Preferably using alkali metal salts of alcohol or amine, or an organic base, and ethanol as a solvent. Thus, for example, the cyclization reaction is carried out by refluxing in ethanol and in the presence of potassium tert-butoxide or sodium ethoxide. Also, compounds of formula I may be obtained directly by cyclization reaction of corresponding compounds of the formula ID. Generally, this reaction is carried out by heating the formula ID in a mixture of P2O5, water and tertiary amine, especially dimethyleyelohexylamine at 10CTC to 300"C . In an alternative procedure, the reaction may be carried out at room temperature or by heating in an alka line hydrogen peroxide water solution, for example a mixture of hydrogen peroxide and urea. The said reaction may also be carried out at room temperature or by heating under anhydrous or hydrous acidic-conditions generally using hydrochloric acid. The specific example of compounds of formula I wherein R' is S02NRI1Rlz' may be prepared by following process. Compounds of formula IC can be readily prepared from compounds of the formula IF and the IE wherein RJ i s H, wherein R1, R2, RJ and R4 are defined as previous. And then compounds of the formula IB are prepared by the reaction of compounds of the formula IC with chlorosulfonic acid: wherein R1, R2, R3 and R4 are defined as previous. The reaction is generally carried out by heating the formula IC in the presence of an excess amount of chlorosulf onic acid. Also, the said reaction may be performed in solvent, of dichloromethane, chloroform, and other inert or polar, non-proton solvents. In particular when the reactant has a poor solubility in chlorosulfonic acid, using above-mentioned solvents seem to be more important. The reaction can be carried out at the temperature as high ay 100°C without producing any by-products, but generally in ice bath. Acylation reaction is carried out by reacting the compounds of the formula IB with proper amines to obtain the compounds of formula I wherein R5 is SC^NR^R"12, and R11, R1'" are defined as previous. The said acylation reaction may be performed in the solvents of dichloromethane, chloroform, tertiary amine and other inert or polar non-proton solvents at -78°C to 100°C using equal or excess amounts of amines. The excess amount of amine is used not only as a reactant, but also a solvent. Either, compounds of the formula I are prepared by reacting formula IG with compounds of formula IH, compound IG is compound I wherein R3 is H: wherein R1, R2, R4 and R5 are defined as previous, wherein X represents Cl, Br or I; RJ is defined as previous. The said reactions are carried out by heating reflux in the solvents of non-polar proton solvents with organic or non-organic base as catalyst, generally alkali carbonate such as potassium carbonate in ketone solvents such as acetone. Optionally, compounds of the formula I can be converted into the corresponding salts by reacting with pharmaceutically acceptable acids. The intermediates of formula IE are prepared from corresponding aromatic carboxylic acid that .1 y commercially available and thionyl chloride, oxalyl chloride by conventional synthesis method, of acyl chloride. If using oxalyl chloride, the reaction should be carried out in the non-proton solvents such as dichloromethane, chloroform, toluene etc. at the temperature of -10°C to 60 °C for 2-10 hours using an equal or excess (no more than 4 fold) amount of oxalyl chloride in the presence of 0.0.S-1 equivalent of dimethyIformamide as a catalyst. The said reaction solutions may be directly used in the preparation of the formula ID or distilled under the reduced pressure to prepare the purified compounds. If using thionyl chloride, the reaction should be performed in the non-proton solvents such as dichloromethane, chloroform, toluene etc., or the thionyl chloride itsel.f: is used as solvent, and better, under the conditions of reflux for 0.5-3 hours. The obtained solutions may be directly used in the preparation of the formula ID, or distilled under the reduced pressure to prepare the purified compounds. Intermediates of the formula IF used may be synthesized readily from malononitrile and correspondingly substituted 2-aminoketones by conventional synthetic procedures in accordance with literatures described below: Wiley R.H., etal, J Am. Chem. Soc, 1948. 70, 2005; Johnson R.W. etal, J Heterocyclic Chem. 1997, 14, 383; and Wamhof f H.et al, Synthesis 1976, 51. The reaction may be carried out in water in the presence of alkali metal hydroxide such as potassium hydroxide or sodium hydroxide etc. as the catalyst at the temperature of 4 °C to 60 °C . The reaction solution is diluted and filtrated, and dried to obtain the product. If the 1ow water-soluble substituted 2-aminoketones is used, the reaction may be carried out either in two phases of both water and organic reagents in the presence of phase transfer catalysts, or in organic solvents in the presence of nitrogenous organic base such as pyridine, triethyl ami ne as catalyst. The resulting compounds can be purlfied by recrystallization. Another aspect of the invention relates to a pharmaceutical composition for treatment of erectile dysfunction in a male animal, including man, comprising a compound of formula I or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable diluent, excipient or carrier. Another aspect of this invention relates to a process for the preparation of a pharmaceutical composition fox treatment or prevention of erectile dysfunction in a male animal, including man, comprising formulating a compound of formula I or a pharmaceutically acceptable salt thereof with pharmaceuticaliy acceptable diluent, excipient or carrier. Although the compounds of the invention are envisaged primarily for the treatment of erectile dysfunction or male sexual dysfunction, they may also be useful for i:he treatment of female sexual dysfunction including orgasmic dysfunction related to clitoral disturbances. Thus, the aspect of this invention provides the use of a compound of formula I for curing or preventing erectile dysfunction in a male animal, including man, and PDE5-related diseases. The aforementioned PDE5-related diseases include male sexual (erectile) dysfunction, female sexual dysfunction, premature delivery, dysmenorrhea, benign prostat ic hyperplasia, bladder obstruction, incontinence, stable ox-unstable angina, hypertension, pulmonary hypertensi on, congestive heart failure, atherosclerosis, stroke, peripheral circulatory disease, low vascular patency, chronic asthma, allergic asthma, bronchitis, allergic rhinitis, glaucoma, disorder of the gastrointestinal movement, forerunner of the seizure, Kawasaki disease, tolerance of nitric acid ester, multiple sclerosis, peripheral nerve syndrome caused by diabetes, Alzheimer disease (AD), acute respiratory system failure, psoriasis, cutaneous gangrene, metastasis of cancer cell, loss of hair, nutcracker oesophagus, anal fissure, arid hypoxia-induced vasoconstriction. The compounds of the invention can exist in tautomeric forms. It is to be understood that all tautomers and other isorners of formula I as well as the mixture thereof fall into the claimed scope of this invention. The compounds of this invention may contain one or more asymmetric centers and thus can exist as epxmers or optical isomers. Furthermore, they are separated into enanti orriers by the conventional methods such as dynamic crystallization or chromatography. Besides, they are synthesized from chiral starting materials or reagents by way of asymmetric synthesis. It is to be understood that all epime rs or optical isomers as well as the mixture thereof fall into the claimed scope of this invention. The compounds of this invention may form pharmaceut i cal.i.y acceptable salts with organic or inorganic acid as weJ.l as o r n fl n i c~* c^ ^~ n ■"> ■"» ^ ■'"■ ^ "^ n ■"* 11 \s- —11 -i It is to be understood that this invention includes both mixtures and separate individual pharmaceutically acceptable salts formed by reacting the compounds of this invention with organic or inorganic alkali as well as organic or inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, tartaric acid, gluconic acid, ]actic acid, maleic acid, fumaric acid, methane-sulfonic acid, hydroxyacetic acid, succinic acid, 4-toluene sulfonic acid, galacturonic acid, glutamic acid, aspartic acid, and the like . Preferred compounds of this invention refer to the following compounds of formula I as well as the pharmaceutically acceptable salts thereof: whereinrR1 is C1-C3 branched or straight chain alky], optionally substituted with one or more groups selected from a group consisted of the following: C^C4 alkyl, 0^-0,. alkoxyl, C1-C4 alkanoyl, substituted phenyl, substituted heterocyclic group, CONR6R7 and NRt'R/; R2 is H; C1-C3 branched or straight chain alkyl optionally substituted with one or more groups selected from a group cylcoalkyl; or R10 and R11 take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4-N (R13) -piperazinyl; or Ri0 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piper idyl, morpholinyl, or 4-N (R13) -piperazinyl; the said groups are optionally substituted with OH,CN, CO;L>Rh, Ci^Ci branched or straight chain alkyl, Cj-C? alkoxyl, NR'^R1'1, or CONRi4R15; substituted phenyl, substituted heterocyclic group, or Ci-C6 branched or straight alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are further substituted with OH, CO2Rb, NRi4RJ'\ CONR14R15, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group; R12 is H; Ci^Ce branched or straight chain alkyl which may be optionally substituted with C--C3 alkyl or C1-C4 alkoxyl, the said alkyl and alkoxyl are substituted with phenyl, hydroxyl; C2^C6 alkenyl or Cj^Ce, cylcoalkyl; R13 is H; Cj-Ce branched or straight chain alkyl; C;--~Ch branched or straight chain alkyl substituted wi th C_i-C, alkoxyl; C2~C6 branched or straight chain alkyl substituted with hydroxyl; C2~C6 branched or straight chain alkyl substituted with NR14Rih; C2^C3 branched or straight chain alkyl substituted with phenyl; Ci^Ce branched or straight chain alkyl substituted with CONR^R1'1; CO.-.R8, CONR'^R1'1, CSNRi4Ri5 or C(NH) NR14R15); C.r-C3 halogenated branched or straight chain alkyl; Co-C6 alkenyl; C?-Co alkynyl or Cj-Cti cylcoalkyl; R and R15 are each independently H; Ci~C4 branched or straight chain alkyl; C2-C4 branched or straight chain alkyi substituted with C1-C3 alkoxyl; or C2~C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R1:j together with their attached nitrogen atom form pyrrol inyl, pyrrolinone group, piperidyl, or morpholinyl; The substituted phenyl refers to a phenyl group which is substituted with one or more groups selected from Cj^CU alkoxyl, halogen, CN, CF3, OCF^, or Cj -C4 branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxide thereof; or penta tornic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen and sulfur atoms; the subs tituents on the heterocyclic ring are Ci -C4 branched or straight chain alkyl, Ci^C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Ci~C,j alkoxylamino. In the more preferred embodiment, compounds of the general formula I and their pharmaceutically acceptable salts as follows: I wherein R1 is C0-C3 branched or straight chain alkyl which may be optionally substituted, with one or more qroups selected from substituted heterocyclic group and NRr'R'; R2 is H; R^ is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C1-C4 cycloalkyl; C — C] alkenyl; C?~C4 alkynyl; R4 is C2-C4 branched or straight chain alkyl, which may be optionally substituted with Cj-C^ alkoxyl; C0-C4 alkenyl; C2-C4 alkynyl; R] is SO2NR10R1J; Rb and R1 together with their attached nitrogen atom form a pyrrolinyl, piperidyl or morpholinyl; R8 is H or C1-C4 branched or straight chain alkyl; R10 and R11 are each independently H or Cx~Ci..? branched or straight chain alkyl; Cj^C^ cylcoalkyl; or R'L and RM ttike together to forma pyrrolinyl, pyrrolinone group, piperi.dyl, morpholinyl, 4-N (Rn) -piperazinyl; or Rlu arid R' ! toqe I:her with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, or 4-N (RJ3) -piperazinyl; the said groups are optional ly substituted with OH,Ci^C4 branched or straight chain alkyl, C1-C3 alkoxyl, NR14R15, or CONR14R15; substituted phenyl, substituted heterocyclic group, or CL-C6 branched or straight alkyl optionally substituted with substituted phenyl, substituted heterocyclic group, the said groups are further substituted with OH, CO2R8, NRi4R15 or CONR]V4, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl; R1- is H; Ci~C3 branched or straight chain alkyl; C-^Cj branched or straight chain alkyl substituted with C, -C -; alkoxyl; C2^C3 branched or straight chain alkyl substituted with OH; C2~C6 branched or straight chain alkyl substituted with NR14R15; C2^C^ branched or straight chain al kyl substituted with phenyl; Ci^C^ branched or straight chain alkyl substituted with CONR14RJ\- CO?R8 or CONRi4Rrj; R14 and R15 are each independently H; C1-C4 branched or straight chain alkyl; C^^-C^ branched or straight chain alkyl substituted with Ci~C3 alkoxyl; or C7-C4 branched or stra ight chain alkyl substituted with OH; or R14 and RL"* together with their attached nitrogen atom form a pyrrol inyl, pyrrol inone group, piperidyl or morpholinyl; the substituted phenyl refers to a phenyl group which is substituted with one or more substituents selected from a group consisted of Ci~C4 alkoxyl, halogen, CN, CF:i/ OCF-j, and C1-C4branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms and the oxide thereof; or pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituents on the heterocyclic ring are Cj ~C4 branched or straight chain alkyl, C.1.-C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Cj-C.i alkoxylamino. Especially preferred compounds of invention include: 2-[2-ethoxyl-5~(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-methoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3, 7-dihydropyrrolo [2, 3-d] pyrirnid.in-4-one, the monohydrochloride, dihydrochlori de and other possible hydrochloride thereof; 2-[2-n-propoxy-5-(4-ethylpiperazinyl-l-sulfonyJ)phenyl] -5-methyl-7-n-propyl-3,7-dihydropyrrolo[2 , 3-d]pyrimi din -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-allyloxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenylJ-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, and the monohydrochloride, dihydrochlori.de and 2-{2-ethoxyl-5-[3-(2-oxy-pyrrolidin-l-yl)-n-propylamino -N-sulfonyljphenyl}-5-methyl-7-n-propyl-3, 7-dihydropyrr olo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2~{2-ethoxyl-5-[2-(pyrrolidin-1-yl)-ethylamino-N-sulfon yl]phenyl}-5-methyl-7-n-propyl-3,7-dihydropyrrolo \2, 3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(morpholino-4-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3~d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2- f2~ethoxyl-5- (3- (morpholin-4-yl) -n-propylainino-N-su.il: onyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo [2,3 -d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof:; 2- [2-ethoxyl-5-(2-(morpholin-4-yl)-ethylamino-N-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(2,6-dimethylmorpholino-N-sulfonyl)pheny 1]-5-methyl-7-n-propyl-3/7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, d_i hydrochloride: and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(l-benzylpiperidyl-4-aminosulfonyl)pheny 1]-5-methyl-7-n-propyl-3, 7-dihydropyrrolo[2, 3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl~5-(2-(piperidin-1-yl)ethylamino-1-sulfonyl )phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochlori.de and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-benzylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-phenylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(piperazinyl-1-sulfonyl)phenyl]-5-methyl -7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-benzo[1,3]dioxol—5-yl-methylpiperaz in yl-1-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropy rrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[4-(3-phenyl-n-propan-l-yl)piperidyl-1-sulfonyl]phenyl-5-methyl-7-n-propy1-3, 7-dihydropyrrolo[ 2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(n-propylamino-1-sulfonyl)phenyl]-5-meth yl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2- [2-ethoxyl-5-(N,N-di(2-hydroxyethyl)aminosulfonyl)phe nyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[ 2, 3-dJpyrim idin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-methyl]aminosulfon yl}phenyl-5-methyl-7-n-propyl-3/7~dihydropyrroio[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-ethyl]aminosulfony 1}phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-n-butyl]aminosulfo nyl}phenyl-5-methy1-7-n-propyl-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2~ethoxyl-5-(p-ethoxylcarboxylphenylamino)-N-sulfony 1]phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-dJ pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hycirochloride thereof; 2-[2-ethoxyl-5-(o-benzoylphenylamino)-N-sulfonyl]phenyl -5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2- [2-ethoxyl-5- (N2-acethydrazido) -Nl-sulf onyl] phenyl - 5)-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride and dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(2-dimethylaminoethylamino)-N-sulfonyl]p henyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyri midin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -ethyl-7-n-propyl-3/7-dihydropyrrolo[2,3-d]pyrimicin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -morpholinomethyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2~ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 - (pyrimidinyl-2 ) -methyl-7-n-propyl~3, 7-dihydropyrro.lo [2 ,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; and 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenylJ-5 -methyl-7-allyl-3, 7-clihydropyrrol o [2, 3-d] pyrimidin-4-on e, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof. The compounds of general formula I can not only be prepared into orally-administrated solid formulations, such as the tablets, pills, capsules and powder, but also liquid ones, such as suspensions, solution, emulsion and syrup. All of these formulations may comprise a variety of conventional excipients, such as the wetting agents, sweet-enhancers, aromatics and preservatives, etc., they may also comprise some other conventional functional excipients, such as the fillers (starch and carbohydrates), binders (carboxymethylcellulose etc.), dispersants (calcium carbonate and sodium carbonate etc. ) , di Luents (glycero 1 ) , absorption enhancers (quaternary ammonium compounds), lubricants (stearate) and absorption agents (kaoi i n) . The compounds of the formula I can be prepared into ointment, for external use. Likewise, they can be also prepared into intravenous injections. Generally, for human, oral administration of the compounds of this invention is the preferred route, being the most convenient route and avoiding the disadvantages associated with administration in corpus cavernosum. In circumstances where the patients suffers from a swallowing disorder or from impairment of drug absorption after oral administration, the drug may be administrated parenterally, e.g. sublingually, buccally, transdermally or injection. For veterinary use, a compound of formula I or a non-toxic salt thereof is administered as a suitable acceptable formulation in accordance with common veterinary practice and the veterinary surgeon will determine the dose range and route of administration, which wi] 1 be the most appropriate for a particular male animal. Furthermore, none of any obvious sign of adverse acute toxicity is shown for the compounds of this invention tested in rat and dog, both intravenously (i.v.) and orally (p.o.) at up to 3 mg/Kg. For the situation of mice, no deaths occurred after doses of up to lOOmg/Kg i.v.. The LD Best modes for carrying out the invention Now, the preparing methods of the compounds of the present invention are further illustrated by the preparation of 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi]-h -methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride and dihydrochlori.de thereof as example. Example 1 Preparation ot 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi] -5-methyl-7-n-propyl~3, 7-dihydropyrrolo[2,3-d]pyrimidin -4-one, its monohydrochloride and dihydrochloride Route of synthesis Example 2 Experiments of penis erection In order to demonstrate efficacy of the compounds of formula I in treatment of functional impotence, the penis erection experiment was established by using the male rabbit as experimental model cross reference to Bischoff's method. (Bischoff E. ; Schneider K, International Journal of Impotence Research, 2 0 01, 13, 2 30-2 35) The hydrochloride , of 3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one derivatives was dissolved into water* and injected to conscious-rabbits intravenously (i.v.) (0.lmg-3mg/kg). Erection was accessed by comparing the length of penis before and at 0, 30, 60, 90 and 120 minutes after intravenous administration of the above-mentioned agents. The results of typica1 compounds in this erectile experiment were listed in table; the good potential in treatment of functional erectile dysfunction with the characteristics of quick onset and prolonged effectiveness, especially the compoundl-lHCl. Example 3 Experiments of the effect of single administration on the coitus function of male rats After purchasing, the male rat and the estrogenized female rat were kept in the same cage for 2 days, and the male rat would acquire the sexual experiences. Then, the female rat was taken out of the cage, and the experiments began after the male rat stayed alone in a cage for 5 days. Each tested compound was orally administered in a dosage of 24mg/kg, the positive group was administered with Sildenafi1 citrate(Viagra) in a dosage of 2 4mg/kg, and the control group was administered with saline at the equal volume ( 0.lml/lOg ) . Fifty minutes after administration, the tested male rats were placed within a observation container (both the diameter and the height of the container were 2 4cm) , and the male rats adapted the new environment for 5 minutes. After that, two estrogenized female rats were placed into the container. The sexual behavior of the male rats in 20 minutes was observed under the non-interfering condition using Panasonic WVCP410/G monitor, the latent-period of straddle, times of straddle, as well as the latent period of the coitus and times of the coitus. All the experiments were carried out at 21-24° C, and completed before 11:00 AM. The comparative results among the compounds of the invention, the blank and the positive control drug Sildenafil citrate were listed in Table 2. The experimental results showed that all the indexes of sexual function of the rats were obviously enhanced after they were administered with compound 1-HC1, namely, the latent period of straddle and coitus were remarkably shortened, and the times of the coitus was obviously increased. And the effect of the compound 1-HCl was stronger than that of the Sildenafil citrate group, especially, the times of the coitus was much more than that of the positive control group(p Table 2. Effect of 3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one derivatives on the indexes of sexual function of the male rats (average valuesistandard deviations) Groups Number the latent times of the latent. timos of of rats period of straddle period of the coi t us straddle the co;i tus (m i n) (m i n ) saline 17 8. 9 ±3. 6 9 7. 1 ±3.62 1 6.2±4 . 02 3.4 ±4 . 6 4 Compound 1 3 . "1 .1. 9 2 . 6± 1 . 13 7 . 6±2 . 70 7 . 1 ±5 . 62 1-HC1 8 . 77+" Compound S 6. 4 ±3. 07 8 . 0±3. 9 3 8. 8 ±5. 8 b 9.018 . :,0 6-KCJ Sj Idenaf 11 19 5 . 0 ± 4.74* i 2 . 7 ± 7.18 8 . 2 ± 4 . 02 ** 8 . 7 ± r>. >■! );i- c :L 1; r a t Q Compared with the group of saline, P Example 4 The bioactivity inhibiting phosphodiesterase of compounds of formula I The bioactivity inhibiting phosphodiesterase 5 (PDES) of compounds of formula 1 was measured cross the reference of methods (Hidaka H, et al Biochirn. Biochim. Biophys. Acta, 1976, 429, 485; Kim D-K, et al. , Bioorg. Med. Chem. 2001, 9, 3013) . The inhibiting activity of PDE5 was deterrni ned using SPA technique and the method of chemical fluorescence. The method was as follows: firstly, the reaction time curve and the enzyme concentration curve of PDES reaction system were determined by Microplate Scintillation & Luminescence-Counter (TopCount Counter) , by which the optimal reaction condition was determined. Under the optimized conditions, the inhibition experiments on PDES were carried out.The results showed that compound I had stronger inhibiting rate on phosphodiesterase 5 than that of sildenafil. For example, when the concentration of compound 1-HC1 was 10~Bmol/L, the inhibiting rate of compound 1-HC1 on PDES was 65.62%, but the inhibiting rate of sildenaf11 on PDE5 was 31.67% . We claim: l.A compound of the general formula 1 : wherein R1 is H; Ci~C4 branched or straight chain alkyl; C\| -C4 halogenated branched or straight chain alkyl; C2~C6 alkenyi ; C2-C4 alkynyl; pyridyl, pyrimidinyl,imidazolyl; except H, the above substituents may be optionally substituted with one or more following groups: halogen, cyano, nitro, hydroxyl, carboxyl, guanidino, C.1-C4 alkyl, C1-C4 alkoxyl, C1-C4 alkanoyl, C3-O, cycloalkyi, substituted phenyl, substituted heterocyclic group, CONR'R6, NR-R", CO?R7, NHSO2RH or SO2NR9R10; R": is H; Cj_-C3 branched or straight chain alkyl; C]~-C R3 is H; C]-C6 branched or straight chain alkyl which may be optionally substituted with C3-C^ cycloalkyl or C1-C4 alkoxyl; C2^C4 alkenyl; C2^C4 alkynyl; R is H; Ci~C6 branched or straight chain alkyl which may be optionally substituted with C3-C6 cycloalkyl or C]^C4 alkoxyl; C2~C4 alkenyl; C2~C4 alkynyl; RJ is H; C1-C4 branched or straight chain alkyl which may be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO?RM; C2-C4 alkenyl which may be optionally substituted wit.}) CN,CONR6R7 or CO2R8; C2-C4 alkoxyl optionally substituted with NR6R7; (C2-C3 alkoxyl) C1-C2 branched or straight chain alkyl optionally substituted with OH or NR6R7; CONR6R7; CO2RH; halogen; NRflR7; NHSO2NR6R7; NHSO2R9; SO2NRl0Rri; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazoiyl, thienyl, or triazolyl, either of which is optionally substituted with methyl; R6 and R; are each independently H or C1-C4 branched or straight chain alkyl; or R6 and R; together with thei r attached nitrogen atom form pyrrolinyl, piperidyl, morpholinyl, 4-N(R12)-piperazinyl or imidazolyl, either of which is optionally substituted with methyl or hydroxyl; R8 is H; Ci^Cfi branched or straight chain alkyl optionally substituted with C1-C4 alkoxyl, C1-C4 alkylamino, dialkylamino; substituted phenyl and substituted, heterocyclic group in which the substitut(s) on the ring of substituted phenyl and substituted heterocyclic group are defined as the above; R9 is C1-C3 alkyl optionally substituted with NR6R7; R10 and R11 are each independently H or Cj-C12 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C2~C6 alkenyl; C2^C6 alkynyl or C3-C6 cycloalkyl; or R10 and R!1 take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4-N (R13) -piperazinyl; or R10 and Rl1 together with their attached nitrogen atom form a pyrrolinyl, pyrrol inone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl which are optionally substituted with OH, CN, CO2Rb, Ci~C4 branched or straight chain alkyl, Ci~C3 alkoxyl, NRI4RLS or CONR^R1'1; substituted phenyl, substituted heterocyclic group, or C[-C6 branched or straight chain alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are optionally further substituted with OH, CO2R8, NRJVb, CONR14RJ5, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group; R12 is H; Ci^Cebranched or straight chain alkyl which may be optionally substituted with phenyl, C?~Ci alkyl substituted by hydroxyi, or C^Q alkoxyl; Ct ~C3 fluoroalkyl; C2-Cf, alkenyl; C2^C6 alkynyl; or C3-C6 cycloalkyl; R1 'is H; CJ-CG branched or straight chain alkyl; C2^C6 branched or straight chain alkyl substituted with C1-C3 alkoxyl; C2-C;, branched or straight chain alkyl substituted with hydroxy L ; C2--C^ branched or straight chain alkyl substituted with NR'4RJi\|; C2-C6 branched or straight chain alkyl substituted with phenyl; Ci^Cg branched or straight chain aikyi substituted with CONR14R15; C-2^C6 branched or straight chain hydrocarbyl substituted with CO2R8; C2-C6 branched or straight chain hydrocarbyl having substituted phenyl or substituted heterocyclic group as substituent; CO-R8, CONRMR15, CSNRI4R15 or C (NH) NR14R15; C^^ halogenated branched or straight chain alkyl; C2~C6 alkenyl; Co^C. alkynyl or C3-C6 cylcloalkyl; or polyethylene glycol group (n=2~20) , which is optionally substituted with C.^Cs alkyl on its terminal; RJ4 and Rlb are each independently H; Ci~C4 branched or straight chain alkyl; C2-C4 branched or straight chain alkyl substituted with C3/-C3 alkoxyl; or C2-C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl; and the substituted phenyl refers to a phenyl which i s substituted with one or more groups selected from Cj -C,-i alkoxyl, halogen, cyano-, CF3/ OCF3, C1-C4 branched or straight chain alkyl on the phenyi ring; The substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxides thereof; pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituting groups on the heterocyclic ring are CL-C; branched or straight chain alkyl, C1-C4 alkoxyl, ami no, as well as C]~C4 branched or straight chain alkyl amino, Cj-C/j alkoxylamino group; Or their pharmaceutically acceptable salts. 2.The compound according to claim 1,wherein:R1 is Ci -C . branched or straight chain alkyl optionally substituted with one or more groups selected from a group consisted of the following: C-j^C4 alkyl, Ci~C4 alkoxyl, C]-~C4 alkanoyl, substituted phenyl, substituted heterocyclic group, CONR6R7 and NR6R7; R" is H; C1-C3 branched or straight chain alkyl optionally substituted with one or more groups selected from a group consisted of the following: substituted phenyl, substituted heterocyclic group, CONR6R;, and NRbR;; R is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C3-C4 cycloalkyl, CL^C'.: alkoxyl; C2~C4 alkenyl; or C2-C4 alkynyl; R':1 is H; CJ.-C4 branched or straight chain alkyl which may be optionally substituted with C3-C5 cycloalkyl or Cj -C:: alkoxyl; C-^C4 alkenyl; or C2^C4 alkynyl; RLl is H; C]-C4 branched or straight chain alkyl which may be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO:!RS ; C2-C4 alkoxyl optionally substituted with NR6R7; NRf'Rv; NHSO-NR6R7; NHSO2R9; SO2NR10Rn; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazoiyl, thienyl or triazolyl, either of which is optionally substituted with methyl; R3 and R are each independently H; C1-C4 branched or straight chain alkyl, or R and R together with their attached nitrogen atom form a pyrrolinyl, piperidyl, morpholinyl, 4-N (R '■) -piperazinyl or imidazolyl, either of which Is optionally substituted with methyl and hydroxyl; R5 is H or C1-C4 branched or straight chain alkyl; R9 is C.1.-C3 alkyl optionally substituted with NR6R7; R""" and RlL are each independently H or Ci~Ci2 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C2~C6 alkenyl; C-^CG alkynyl or Cr^C,, cylcoalkyl; or R10 and R11 taken together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4~N (R13)-piperazinyl; or R10 and Ru together with their attached nitrogen atom form a pyrrolinyl, pyrrolidone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl; the said groups are optionally substituted with OH,CN, CO2RH, CJ^C^I branched or straight chain alkyl, C1/-C3 alkoxyl, NR R1 ', or CONR^R15; substituted phenyl, substituted heterocyclic group, or C]-C6 branched or straight alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are further substituted with OH, CO;^RJ, NR *'R ", CONRi4R15, or linked together with another substituted phenyl or substituted heterocyclic group by a ca rbonyl group; R ^ is H; C_i-C6 branched or straight chain alkyl which may be optionally substituted with C2-C3 alkyl or Ci^C^ alkoxyl, the said alkyl and alkoxyl are substituted with phenyl, hydroxyl; C2~C6 alkenyl or C3-C6 cylcoalkyl; R13 is H; Ci~C6 branched or straight chain alkyl; C?^Cf-( branched or straight chain alkyl substituted with Ci -C_ R14 and RL5 are each independently H; C.i^C^ branched or straight chain alkyl; Co^-C^ branched or straight chain al kyl substituted with C1-C3 alkoxyl; or C2^C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R"! ' together with their attached nitrogen atom form pyrrolinyl, pyrrolinone group, piperidyl, or morpholinyl; The substituted phenyl refers to a phenyl group which is substituted with one or more groups selected from Cj_~C; alkoxyl, halogen, CN, CF3, OCF3, or C.1-C4 branched 01: straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxide thereof; or pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen and sulfur atoms; the substituents on the heterocyclic ring are C^C^ branched or straight chain alkyl, Ci~C4 alkoxyl, amino, as well as Ci~C4 branched or straight chain alkyl amino, C1-C4 alkoxylamino. 3.The compound according to claim 1 or 2, wherein: RJ is C2~C3 branched or straight chain alkyl which may be optionally substituted with one or more groups selected from substituted heterocyclic group and NR6R ; R2 is H; R3 is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C3-C4 cycloalkyl; CS-C,i alkenyl; C?_^C^ alkynyl; R4 is C2~C4 branched or straight chain alkyl, which may be optionally substituted with Ci~C3 alkoxyl; C0-C4 alkenyl; C2-C4 alkynyl; R5 is SO,?NRJ0R]1; R6 and R; together with their attached nitrogen atom form a pyrrolinyl, piperidyl or morpholinyl; R8 is H or Ci~C4 branched or straight chain alkyl; R10 and RJ l are each independently H or C\.'-C]2 branched or straight chain alkyl; C3-C6 cylcoalkyl; or R10 and RJ' take together to forma pyrrolinyl, pyrrolinone group, piper.idyl, morpholinyl, 4-N (R13) -piperazinyl; or R10 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, or 4-N (R )-piperazinyl; the said groups are optionally substituted with OH,C]_~C4 branched or straight chain alkyl, C^C-3 alkoxyl, NR14R15, or CONR14Rif); substituted phenyl, substituted heterocyclic group, or Ci~Ce branched or straight alkyl optionally substituted with substituted phenyl, substituted heterocyclic group, the said groups are further substituted with OH, CO2R8, NR14RJb or CONR13R1/1, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl; RiJ is H; C1-C3 branched or straight chain alkyl; C?-C{ branched or straight chain alkyl substituted with Cj~C} alkoxyl; C^^C.s branched or straight chain alkyl substituted with OH; Co^-Ce branched or straight chain alkyl substituted with NRL4R15; C2^C3 branched or straight chain a] kyl substituted with phenyl; Ci^Cs branched or straight chain alkyl substituted with CONR14R15; CO2R8 or CONR14R15'; R34 and R1" are each independently H; C1-C4 branched or straight chain alkyl; C2^C4 branched or straight chain alkyl substituted with C1-C3 alkoxyl; or C2-C4 branched or straight chain alkyl substituted with OH; or R1A and R15 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl; the substituted phenyl refers to a phenyl group which is substituted with one or more substituents selected from a group consisted of Ci~C4 alkoxyl, halogen, CN, CF3, OCF-U and C1-C4branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms and the oxide thereof; or pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituents on the heterocyclic ring are C-i ~C/j branched or straight chain alkyl, C1-C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Ci -C 4 . The compound according to any one of claims 1-3, wherein the compound is selected from a group consisting of: 2- [2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi]-5 -methyl-7- n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-methoxyl-5~(4-ethylpiperazinyl-l-sulfonyl)phenyj.-5-methyl-7-n-propyl-3,7-dihydropyrrolo\2,3-d]pyrimidin-4-one, and the hydrochloride thereof; 2-[2-n-propoxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi] -5~methyl-7-n-propyl~3,7-dihydropyrrolo[2, 3-d]pyrimidin -4-one, and the hydrochloride thereof; 2~ [2-ally.loxy-5- (4-ethylpiperazinyl-l-sulf onyl) phenyi] -5-methyl-7-n-propyi-3, 7-dihydropyrrolo [2, 3-d] pyrimid.i n- 4-one, and the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-n~propoxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl.} -5-ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-methylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidi n-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-methylpiperazinyl-l-sulfonyl)phenylJ-5-ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride, dihydrochloride and other-possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-ethoxycarbonylpiperazinyl-l-sulfonyi) phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]py rimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2~[2-ethoxyl-5-(4-(2-hydroxyethyl)piperazinyl-1-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(pyrrolidinyl-1-sulfonyl)phenyl]-5-me thy 1-7-n- propy1-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[3-(2-oxy-pyrrolidin-l-yl)-n-propylamino -N-sulfonyl]phenyl}-5-methyl-7-n-propyl-3, 7~dihydropyrr olo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[2-(pyrrolidin-1-yl)-ethylamino-N-sulfon yl]phenyl}-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(morpholino-4-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(3-(morpholin-4-yl)-n-propylamino-N-suli onyl)phenyl]-5-methyl-7-n-propyl-3/ 7-dihydropyrrolo[2,3 -d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(2-(morpholin-4-yl)-ethylamino-N-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(2,6-dimethylmorpholino-N-sulfonyl)pheny 1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(l-benzylpiperidyl-4-aminosulfonyl)pheny 1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2- [2-ethoxyl-5- (2- (piperidin-1-yl) ethylamino-1-sulf oriyl )pheny1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2~[2-ethoxyl-5-(4-benzylpiperazinyl-l-sulfonyl)phenyJ. ]-5-methyl-7-n-prGpyl~3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-f2-ethoxyl-5-(4-phenylpiperazinyl-l-sulfonyl)pheny1}-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4~one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(piperazinyl-1-sulfonyl)pheny1]-5-methyl -7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-benzo[1,3]dioxol—5-yl-methylpiperazin yl-1-sulfonyl)phenyl]-5-methyl-7-n-propyl-3, 7-dihydropy rrolo[2,3-d] pyrimidin~4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[4-(3-phenyl-n-propan-1-y1)piperidyl-1-s ulfonyl]phenyl}-5-methyl-7~n-propyl-3,7-dihydropyrrolo f 2, 3-d]pyrimidin~4~one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(n-propylamino-l~sulfonyl)phenyl]-5-meth yl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2~ethoxyl-5-[N,N-di(2-hydroxyethyl)aminosulfonyl]phe nyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2, 3~d]pyrimi din-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-methyl]aminosulfon yl}phenyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-ethyl]aminosulfony 1}phenyl-5-methyl~7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-n-butyl]aminosulfo nyl}phenyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(p-ethoxylcarboxylphenylamino)-N-sulfony 1]phenyl-5-methyl~7-n-propyl-3,7-dihydropyrrolo f2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(o-benzoylphenylamino)-N-sulfonyl]phenyl -5-methyl-7~n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(N2-acethydrazido)-Nl-sulfonyl]phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride and dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl~5-(2-dimethylaminoethylamino)-N-sulfony]Jp henyl-5-methyl-7-n-propyl-3f 7-dihydropyrrolo[2,3-d]pyri midin-4-one, the monohydrochloride, dihydrochJ oride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyJ J-5 -ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-onef the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2~[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -morpholinomethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4~ one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -(pyrimidinyl-2)-methyl-7-n-propyl-3r7-dihydropyrrolo [2 ,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof; and 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -methyl-7-allyl-3,7-dihydropyrrolo[2 , 3-d]pyrimidin-4-on e, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof. 5. A process for preparing the compounds of general formula I according to claim 1, comprising: compound IE is reacted with compound IF: in an inert solvent in the presence of an organic base as a catalyst as well as acid neutralizer at -2 0°C to 8CTC, wherein R1, R2, R3, R4 and R5 are defined as claim 1, to obtain compound ID: wherein R1, R2, R3, R4 and R5 are defined as the above, then compound IA may be prepared by heating compound ID in an acidic aqueous solution: IA wherein R1, R2, R3, R4 and R5 are defined as the above, and then a cyclization reaction of compound IA is carried out by heating and refluxing in an appropriate soluti on under acidic, basic or neutral condition to obtain compound of formula I: wherein R1, R2, R3, R4 and R5 are defined as the above; or, compound of formula I is obtained directly by cyclization of the corresponding compound ID under conditions as follows: a) heating to 100~300°C in mixture of phosphorus pentoxide, water and tertiary amine, or, b) reacting at room temperature or reacting by heating in basic hydrogen peroxide aqueous solution, or, c) reacting at room temperature or reacting by heating under acidic hydrous or anhydrous condition; or, specific example of compounds of general formula I wherein R' is SO^NR R~ may be prepared by processes as follows: compound IC is obtained by reaction between compound IF' and compound IE wherein R5 is H; wherein R1, R2, R3 and R4 are defined as the above, then compound IB is obtained by reacting compound IC with ch.lorosulfonic acid alone or in dichloromethane, chloroform, and other inert or polar non-proton solvents, wherein R1, R2, R- and R4 are as previously defined, and then acylation reaction occurs between compound IB and proper amines in dichloromethane, chloroform, tertiary amine or other inert or polar non-proton solvents at -78 °C to 100°C to obtain compound of formula I wherein R'1 is SO2NRuRl2, wherein R11 and Rl2 are defined as claim 1; or, compound IG wherein R1, R2, R3, R4 and Rs are defined as claim 1, reacts with compound IH in the solvents of polar non-proton solvents in the presence of the base as catalyst to obtain compound of formula I, wherein X represents Cl, Br or 1 , R" is defined as claim 1; Optionally, compounds of the formula I can be converted into the corresponding salts by reacting with pharmaceuticaily acceptable acids. 6 .A pharmaceutical composition containing the compound according to any one of claims 1-4 as active ingredient, and pharmaceuticaily acceptable excipient. 7.A veterinary drugs composition containing the compound according to any one of claims 1-4 as active ingredient, and veterinarily acceptable excipient. 8. Use of compounds according to any one of claims 1-4 for the manufacture of a medicament for treatment or prevention of the diseases related with phospholipase and the function thereof. 9. The use according to claim 8, wherein the diseases includes: male sexual (erectile) dysfunction, female sexual dysfunction, premature delivery, dysmenorrhea, benign pros tat ic hyperplasia, bladder obstruct; ion, incontinence, stable or unstable angina, hypertension, pulmonary hypertension, congestive heart failu re, arteriosclerosis, stroke, peripheral circulatory disease, low vascular patency, chronic asthma, allergic asthma, bronchitis, allergic rhinitis, glaucoma, disorder of the gastrointestinal movement, forerunner of the sei zure, Kawasaki disease, tolerance of nitric acid ester, multiple sclerosis, peripheral nerve syndrome caused by diabetes, Alzheimer disease (AD), acute respiratory system failure, psoriasis, skin gangrene, metastasis of cancer cell, .loss of hair, nutcracker esophagus, anal fissure, and hypoxia-induced vasoconstriction. 10.Intermediates IA-IG for the manufacture of compound ot formula I according to claim 1:

Full Text

2-substituted phenyl-5, 7-dihydrocarbyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one derivatives, the preparation and the pharmaceutical use thereof
Field of invention
The present invention relates to 2-substituted phenyl-5,7-dihydrocarbyl-3/7-dihydropyrrolo[ 2,3-d]pyrim idin-4-one derivatives, the process for their preparation, the composition containing them, and the use for treatment and/or prevention of sexual dysfunction and other diseases related to phospholipase 5.
Background of invention
Sildenafil, disclosed in WO942 8 902, is first kind of orally-administrated potent inhibitors of phospholipase 5 in treatment of the erectile dysfunction of man. By inhibiting the phospholipase 5 in corpus cavernosum, it can achieve the purpose of relaxing smooth muscle in human corpus cavernosum, improving penile hyperemia so as to result in erection. The effective rates of sildenafil in treating male sexual organs erectile dysfunction amount to 30%.
Also, Pfizer Ltd. has developed a series of 1,6-dihydropyrrol [4,3-d] pyrimidin-7-one derivatives, and broadened their therapeutic area where such indi cat ions was thought to be treated by inhibiting phospholipase 5. All of these compounds are disclosed in EP0951098, WO9849116, US6251904, and WO0024745, and the latter two of

patents include the compounds whose substituted phenyl on C-5 is replaced by the substituted pyridin-2-yl. On the basis of the structure of Sildenafil, DONG A PHARMA Co . Ltd. of Korea developed a series of mono substituted derivatives in the nitrogen atom of sulfonylamino group, as disclosed in WO0027848 and WO0198304. Presently, as described in
WO0216364, in order to further enhance water-solubility,
LG Chem . Invest. Ltd. disclosed the derivatJ ves of
1,6-dihydropyrrolo[4,3-d]-pyrimidin-7-one with
polyethylene glycol. In addition,
1,5-dihydropyrrolo[3,4-d]pyrimidin-4-ones and
1,9-dihydropurin-6~ones were developed by Pfizer Ltd. for the treatment of sexual dysfunction(US6100270) . WO016082b disclosed 3,5-dihydropyrrolo[3,2-d]pyrimidin-4-ones are useful for the treatment of impotence. Recently, 3H-imidazo[5,1-f][1,2,4]triazin-4-ones was disclosed by Bayer Co. Ltd. in the patent application DE19881732.
Detailed description of the invention
The object of the present invention is to provide compounds for treatment of sexual dysfunction and other diseases related to phospholipase 5.
Thus, according to one aspect, the invention provides novel aryl substituted 3,7-dihydropyrrolo[2,3-d] pyrimidin-4-ones and their pharmaceutically acceptable salts (also named Yonkenaf il) , the compounds are the

structure of general formula ( I ) :

I
wherein R1 is H; Ci~C4 branched or straight chain alkyl; Ci~C,i halogenated branched or straight chain alkyl; C;^CG alkenyl; C2-C4 alkynyl; pyridyl, pyrimidinyl,imidazolyl; except H, the above substituents may be optionally substituted with one or more following groups: halogen, cyano, nitro, hydroxyl, carboxyl, guanidino, Ci~C4 alkyl, C.i~C4 alkoxyl, C1-C4 alkanoyl, C-^C^ cycloalkyl, substituted phenyl, substituted heterocyclic group, CONR5R6, NR'R^', COR7, NHSO9R8 or SO2NR9R10;
R^ is H; Ci^Cs branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyi; C?-C{, aikenyl ; C-^Ca alkynyl; substituted phenyl; except. H, the above substituents may be optionally substituted w.i th one or more following groups: halogen, cyano-, nitro, hydroxy], carboxyl, guanidino-, Cj -C4 alkyl, Ci -C/j alkoxyl, Cj -Cr{ alkanoyl, C3-C5 cycloalkyl, substituted heterocyclic group, CONR6R7, NR6R7, C0?R8, NHSO2RH or SO2NRl0Rn;
R3 is H; Cj-Ce branched or straight chain alkyl which may

be optionally substituted with C3-C6 cycloalkyl or C1-C4 alkoxyl; C2-C4 alkenyl; C2-C4 alkynyl;
R is H; C1-C6branched or straight chain alkyl which may be optionally substituted with C3-C6 cycloalkyl or Ci^C4 alkoxyl; C2~C4 alkenyl; C2^C4 alkynyl;
R~ is H; C1-C4 branched or straight chain alkyl which may
be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO2R8 ;
C2^C4 alkenyl which may be optionally substituted with CN,CONR6R7 or CO2R8; C2-C4 alkoxyl optionally substituted with NR6Ry; (C2~C3 alkoxyl) C1-C2 branched or straight chain alkyl optionally substituted with OH or NR6R7; CONR6R7; CO,RB; halogen; NR6R7; NHSO2NR6R7; NHSO2R5; SO2NRi0Rjl; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, thienyl, or triazolyl, either of which is optionally substituted with methyl;
R6 and R7 are each independently H or C1/-C4 branched or straight chain alkyl; or R6 and R' together with their attached nitrogen atom form pyrrolinyl, piper idyl , morpholinyl, 4-N(R12)-piperazinyl or imidazolyl, either of which is optionally substituted with methyl or hydroxyl;
R8 is H; Cj-Cfs branched or straight chain alkyl optionally substituted with C]~C4 alkoxyl, C1-C4 alkylamino, dialkylamino; substituted phenyl and substituted heterocyclic group in which the substitut(s) on the ring of substituted phenyl and substituted heterocyclic group are defined as the above;

R9 is C1-C3 alkyl optionally substituted with NR6R7;
R10 and R11 are each independently H or C1/-C12 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C?-C6 alkenyl; C2~-C6 alkynyl or C-^Ce cycloalkyl; or R10 and R11take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholi nyl, 4-N (R13)-piperazinyl; or R10 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholi nyl, or 4-N (R1") -piperazinyl; the said groups are optionally substituted with OH, CN, CO2R(i, Cj-CU branched or straight chain alkyl, Cj^C^ alkoxyl, NR14Rjl or CONR14Ri5; substituted phenyl, substituted heterocyclic group, or Cx-C6 branched or straight chain aikyJ. substituted with substituted phenyl or substituted heterocyclic group, the said groups are optionally further substituted with OH, CO2R8, NR14R15, CONR14Rllj, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group;
R1' is H; Ci-C6 branched or straight chain alkyl which may be optionally substituted with phenyl, C-'-C-] a 1 ky 1 substituted by hydroxyl, or Ci -C4 a.l koxyl; Ci -C3 fluoroa 1 ky 1 ; Co-Ce alkenyi; C2^C6 alkynyi; or C^C^ cycloalkyl; R! Ms H; Ci-C6 branched or straight chain alkyl; C?-C6 branched or straight chain alkyl substituted with C[~C-$ alkoxyl; C:'-Ctl branched or straight chain alkyl substituted with hydroxy.1 ; C2^C6 branched or straight chain alkyl substituted with NR14Rirr); C2^CG branched or straight chain alkyl substituted

with phenyl; Ci^-C^ branched or straight chain aikyl substituted with CONR14R15; Co-C^branched or straight chain hydrocarbyl substituted with CO2RB; C2~C6 branched or straight chain hydrocarbyl having substituted phenyl or substituted heterocyclic group as substituent; COoR8, CONR^R15, CSNR14R1S or C (NH) NRi4Rlb; Ci-C3 halogenated branched or straight chain alkyl; C:.-C6 alkenyl; CS^Cf, alkynyl or C3~Ce cylcloalkyl; or polyethylene glycol group (n=2~20), which is optionally substituted with Cj-~C6 aikyl on its terminal;
R]4 and R15 are each independently H; Ci~C4 branched or straight chain alkyl; C2~C4 branched or straight chain alkyl substituted with C1-C3 alkoxyl; or C2~-C4 branched or straight. chain alkyl substituted with hydroxyl; or Ri1 and Rin together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl; and
the substituted phenyl refers to a phenyJ which is substituted with one or more groups selected from Cj~C] alkoxyl, halogen, cyano-, CF3, OCF'3, C1-C4 branched or straight chain alkyl on the phenyl ring; The substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxides thereof; pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituting groups on the heterocyclic ring are C-I-C
well as C1-C4 branched or straight chain alkyl amino, C1-C4 alkoxylamino group.
In another aspect, the invention provides processes for preparation of compounds of the formula I and intermediates used in the preparation thereof.
The process for preparation of compounds of the general formula I comprises:
The compounds of formula IE with a compound of formula IF

wherein R , Rz, R , R and R~ are defined as previous, are reacted in an inert solvent such as dichloromethane and toluene and the like to produce the compounds of formula ID,
ID Wherein R1, R2, R3, R4 and Rb are defined as previous.

This reaction is carried out in the presence of an organic base such as tertiary amine, pyridine as a catalyst as well
as an acid neutralizer at -20°C to 80°C.
And then compounds of formula IA may be obtained by heating compounds of formula ID in an acidic aqueous solution, generally phosphoric acid aqueous solution:

Wherein R1, R4-, R3, R4 and R5 are as previously defined.
And then the compounds of formula I is obtained by a cyclization reaction of compounds of formula IA :

Wherein R1, R2, R3, R4 and Rs are defined as previous.
The cyclization reaction is similar to a convent: i ona.l method known for synthesis of pyrimidone. The reaction may

be carried out by reflux in an appropriate solution under acidic, basic or neutral condition. Preferably using alkali metal salts of alcohol or amine, or an organic base, and ethanol as a solvent. Thus, for example, the cyclization reaction is carried out by refluxing in ethanol and in the presence of potassium tert-butoxide or sodium ethoxide.
Also, compounds of formula I may be obtained directly by cyclization reaction of corresponding compounds of the formula ID.
Generally, this reaction is carried out by heating the formula ID in a mixture of P2O5, water and tertiary amine,
especially dimethyleyelohexylamine at 10CTC to 300"C .
In an alternative procedure, the reaction may be carried out at room temperature or by heating in an alka line hydrogen peroxide water solution, for example a mixture of hydrogen peroxide and urea.
The said reaction may also be carried out at room temperature or by heating under anhydrous or hydrous acidic-conditions generally using hydrochloric acid.
The specific example of compounds of formula I wherein R' is S02NRI1Rlz' may be prepared by following process.
Compounds of formula IC can be readily prepared from compounds of the formula IF and the IE wherein RJ i s H,

wherein R1, R2, RJ and R4 are defined as previous.
And then compounds of the formula IB are prepared by the reaction of compounds of the formula IC with chlorosulfonic acid:

wherein R1, R2, R3 and R4 are defined as previous.
The reaction is generally carried out by heating the formula IC in the presence of an excess amount of chlorosulf onic acid. Also, the said reaction may be performed in solvent, of dichloromethane, chloroform, and other inert or polar, non-proton solvents. In particular when the reactant has a poor solubility in chlorosulfonic acid, using above-mentioned solvents seem to be more important. The reaction can be carried out at the temperature as high ay

100°C without producing any by-products, but generally in ice bath.
Acylation reaction is carried out by reacting the compounds of the formula IB with proper amines to obtain the compounds of formula I wherein R5 is SC^NR^R"12, and R11, R1'" are defined as previous.
The said acylation reaction may be performed in the solvents of dichloromethane, chloroform, tertiary amine and other
inert or polar non-proton solvents at -78°C to 100°C using
equal or excess amounts of amines. The excess amount of amine is used not only as a reactant, but also a solvent.
Either, compounds of the formula I are prepared by reacting formula IG with compounds of formula IH, compound IG is compound I wherein R3 is H:

wherein R1, R2, R4 and R5 are defined as previous,

wherein X represents Cl, Br or I; RJ is defined as previous.

The said reactions are carried out by heating reflux in the solvents of non-polar proton solvents with organic or non-organic base as catalyst, generally alkali carbonate such as potassium carbonate in ketone solvents such as acetone.
Optionally, compounds of the formula I can be converted into the corresponding salts by reacting with pharmaceutically acceptable acids.
The intermediates of formula IE are prepared from corresponding aromatic carboxylic acid that .1 y commercially available and thionyl chloride, oxalyl chloride by conventional synthesis method, of acyl chloride.
If using oxalyl chloride, the reaction should be carried out in the non-proton solvents such as dichloromethane,
chloroform, toluene etc. at the temperature of -10°C to 60
°C for 2-10 hours using an equal or excess (no more than
4 fold) amount of oxalyl chloride in the presence of 0.0.S-1 equivalent of dimethyIformamide as a catalyst. The said reaction solutions may be directly used in the preparation of the formula ID or distilled under the reduced pressure to prepare the purified compounds.
If using thionyl chloride, the reaction should be performed in the non-proton solvents such as dichloromethane, chloroform, toluene etc., or the thionyl chloride itsel.f: is used as solvent, and better, under the conditions of

reflux for 0.5-3 hours. The obtained solutions may be directly used in the preparation of the formula ID, or distilled under the reduced pressure to prepare the purified compounds.
Intermediates of the formula IF used may be synthesized readily from malononitrile and correspondingly substituted 2-aminoketones by conventional synthetic procedures in accordance with literatures described below:
Wiley R.H., etal, J Am. Chem. Soc, 1948. 70, 2005; Johnson
R.W. etal, J Heterocyclic Chem. 1997, 14, 383; and Wamhof f H.et al, Synthesis 1976, 51.
The reaction may be carried out in water in the presence of alkali metal hydroxide such as potassium hydroxide or sodium hydroxide etc. as the catalyst at the temperature
of 4 °C to 60 °C . The reaction solution is diluted and
filtrated, and dried to obtain the product. If the 1ow water-soluble substituted 2-aminoketones is used, the reaction may be carried out either in two phases of both water and organic reagents in the presence of phase transfer catalysts, or in organic solvents in the presence of nitrogenous organic base such as pyridine, triethyl ami ne as catalyst. The resulting compounds can be purlfied by recrystallization.
Another aspect of the invention relates to a pharmaceutical composition for treatment of erectile dysfunction in a male

animal, including man, comprising a compound of formula I or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable diluent, excipient or carrier.
Another aspect of this invention relates to a process for
the preparation of a pharmaceutical composition fox treatment or prevention of erectile dysfunction in a male animal, including man, comprising formulating a compound of formula I or a pharmaceutically acceptable salt thereof with pharmaceuticaliy acceptable diluent, excipient or carrier.
Although the compounds of the invention are envisaged primarily for the treatment of erectile dysfunction or male sexual dysfunction, they may also be useful for i:he treatment of female sexual dysfunction including orgasmic dysfunction related to clitoral disturbances.
Thus, the aspect of this invention provides the use of a compound of formula I for curing or preventing erectile dysfunction in a male animal, including man, and PDE5-related diseases.
The aforementioned PDE5-related diseases include male sexual (erectile) dysfunction, female sexual dysfunction, premature delivery, dysmenorrhea, benign prostat ic hyperplasia, bladder obstruction, incontinence, stable ox-unstable angina, hypertension, pulmonary hypertensi on, congestive heart failure, atherosclerosis, stroke,

peripheral circulatory disease, low vascular patency, chronic asthma, allergic asthma, bronchitis, allergic rhinitis, glaucoma, disorder of the gastrointestinal movement, forerunner of the seizure, Kawasaki disease, tolerance of nitric acid ester, multiple sclerosis, peripheral nerve syndrome caused by diabetes, Alzheimer disease (AD), acute respiratory system failure, psoriasis, cutaneous gangrene, metastasis of cancer cell, loss of hair, nutcracker oesophagus, anal fissure, arid hypoxia-induced vasoconstriction.
The compounds of the invention can exist in tautomeric forms. It is to be understood that all tautomers and other isorners of formula I as well as the mixture thereof fall into the claimed scope of this invention.
The compounds of this invention may contain one or more asymmetric centers and thus can exist as epxmers or optical isomers. Furthermore, they are separated into enanti orriers by the conventional methods such as dynamic crystallization or chromatography. Besides, they are synthesized from chiral starting materials or reagents by way of asymmetric synthesis. It is to be understood that all epime rs or optical isomers as well as the mixture thereof fall into the claimed scope of this invention.
The compounds of this invention may form pharmaceut i cal.i.y
acceptable salts with organic or inorganic acid as weJ.l as o r n fl n i c~* c^ ^~ n ■*"> ■"» ^ ■'"■* ^ "^ n ■"* 11 \s- —11 -i

It is to be understood that this invention includes both mixtures and separate individual pharmaceutically acceptable salts formed by reacting the compounds of this invention with organic or inorganic alkali as well as organic or inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, tartaric acid, gluconic acid, ]actic acid, maleic acid, fumaric acid, methane-sulfonic acid, hydroxyacetic acid, succinic acid, 4-toluene sulfonic acid, galacturonic acid, glutamic acid, aspartic acid, and the like .
Preferred compounds of this invention refer to the following compounds of formula I as well as the pharmaceutically acceptable salts thereof:

whereinrR1 is C1-C3 branched or straight chain alky], optionally substituted with one or more groups selected from a group consisted of the following: C^C4 alkyl, 0^-0,. alkoxyl, C1-C4 alkanoyl, substituted phenyl, substituted heterocyclic group, CONR6R7 and NRt'R/;
R2 is H; C1-C3 branched or straight chain alkyl optionally substituted with one or more groups selected from a group

cylcoalkyl; or R10 and R11 take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4-N (R13) -piperazinyl; or Ri0 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piper idyl, morpholinyl, or 4-N (R13) -piperazinyl; the said groups are optionally substituted with OH,CN, CO;L>Rh, Ci^Ci branched or straight chain alkyl, Cj-C? alkoxyl, NR'^R1'1, or CONRi4R15; substituted phenyl, substituted heterocyclic group, or Ci-C6 branched or straight alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are further substituted with OH, CO2Rb, NRi4RJ'\ CONR14R15, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group;
R12 is H; Ci^Ce branched or straight chain alkyl which may be optionally substituted with C--C3 alkyl or C1-C4 alkoxyl, the said alkyl and alkoxyl are substituted with phenyl, hydroxyl; C2^C6 alkenyl or Cj^Ce, cylcoalkyl;
R13 is H; Cj-Ce branched or straight chain alkyl; C;--~Ch branched or straight chain alkyl substituted wi th C_i-C, alkoxyl; C2~C6 branched or straight chain alkyl substituted with hydroxyl; C2~C6 branched or straight chain alkyl substituted with NR14Rih; C2^C3 branched or straight chain alkyl substituted with phenyl; Ci^Ce branched or straight chain alkyl substituted with CONR^R1'1; CO.-.R8, CONR'^R1'1, CSNRi4Ri5 or C(NH) NR14R15); C.r-C3 halogenated branched or straight chain alkyl; Co-C6 alkenyl; C?-Co alkynyl or Cj-Cti

cylcoalkyl;
R and R15 are each independently H; Ci~C4 branched or straight chain alkyl; C2-C4 branched or straight chain alkyi substituted with C1-C3 alkoxyl; or C2~C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R1:j together with their attached nitrogen atom form pyrrol inyl, pyrrolinone group, piperidyl, or morpholinyl;
The substituted phenyl refers to a phenyl group which is substituted with one or more groups selected from Cj^CU alkoxyl, halogen, CN, CF3, OCF^, or Cj -C4 branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxide thereof; or penta tornic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen and sulfur atoms; the subs tituents on the heterocyclic ring are Ci -C4 branched or straight chain alkyl, Ci^C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Ci~C,j alkoxylamino.
In the more preferred embodiment, compounds of the general formula I and their pharmaceutically acceptable salts as follows:

I
wherein R1 is C0-C3 branched or straight chain alkyl which may be optionally substituted, with one or more qroups selected from substituted heterocyclic group and NRr'R';
R2 is H;
R^ is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C1-C4 cycloalkyl; C — C] alkenyl; C?~C4 alkynyl;
R4 is C2-C4 branched or straight chain alkyl, which may be optionally substituted with Cj-C^ alkoxyl; C0-C4 alkenyl; C2-C4 alkynyl;
R] is SO2NR10R1J;
Rb and R1 together with their attached nitrogen atom form a pyrrolinyl, piperidyl or morpholinyl;
R8 is H or C1-C4 branched or straight chain alkyl;
R10 and R11 are each independently H or Cx~Ci..? branched or straight chain alkyl; Cj^C^ cylcoalkyl; or R'L and RM ttike together to forma pyrrolinyl, pyrrolinone group, piperi.dyl, morpholinyl, 4-N (Rn) -piperazinyl; or Rlu arid R' ! toqe I:her

with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, or 4-N (RJ3) -piperazinyl; the said groups are optional ly substituted with OH,Ci^C4 branched or straight chain alkyl, C1-C3 alkoxyl, NR14R15, or CONR14R15; substituted phenyl, substituted heterocyclic group, or CL-C6 branched or straight alkyl optionally substituted with substituted phenyl, substituted heterocyclic group, the said groups are further substituted with OH, CO2R8, NRi4R15 or CONR]V4, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl;
R1- is H; Ci~C3 branched or straight chain alkyl; C-^Cj branched or straight chain alkyl substituted with C, -C -; alkoxyl; C2^C3 branched or straight chain alkyl substituted with OH; C2~C6 branched or straight chain alkyl substituted with NR14R15; C2^C^ branched or straight chain al kyl substituted with phenyl; Ci^C^ branched or straight chain alkyl substituted with CONR14RJ\- CO?R8 or CONRi4Rrj;
R14 and R15 are each independently H; C1-C4 branched or straight chain alkyl; C^^-C^ branched or straight chain alkyl substituted with Ci~C3 alkoxyl; or C7-C4 branched or stra ight chain alkyl substituted with OH; or R14 and RL"* together with their attached nitrogen atom form a pyrrol inyl, pyrrol inone group, piperidyl or morpholinyl;
the substituted phenyl refers to a phenyl group which is substituted with one or more substituents selected from a

group consisted of Ci~C4 alkoxyl, halogen, CN, CF:i/ OCF-j, and C1-C4branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms and the oxide thereof; or pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituents on the heterocyclic ring are Cj ~C4 branched or straight chain alkyl, C.1.-C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Cj-C.i alkoxylamino.
Especially preferred compounds of invention include:
2-[2-ethoxyl-5~(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-methoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3, 7-dihydropyrrolo [2, 3-d] pyrirnid.in-4-one, the monohydrochloride, dihydrochlori de and other possible hydrochloride thereof;
2-[2-n-propoxy-5-(4-ethylpiperazinyl-l-sulfonyJ)phenyl] -5-methyl-7-n-propyl-3,7-dihydropyrrolo[2 , 3-d]pyrimi din -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-allyloxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenylJ-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, and the monohydrochloride, dihydrochlori.de and

2-{2-ethoxyl-5-[3-(2-oxy-pyrrolidin-l-yl)-n-propylamino -N-sulfonyljphenyl}-5-methyl-7-n-propyl-3, 7-dihydropyrr olo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2~{2-ethoxyl-5-[2-(pyrrolidin-1-yl)-ethylamino-N-sulfon yl]phenyl}-5-methyl-7-n-propyl-3,7-dihydropyrrolo \2, 3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(morpholino-4-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3~d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2- f2~ethoxyl-5- (3- (morpholin-4-yl) -n-propylainino-N-su.il: onyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo [2,3 -d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof:;
2- [2-ethoxyl-5-(2-(morpholin-4-yl)-ethylamino-N-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(2,6-dimethylmorpholino-N-sulfonyl)pheny 1]-5-methyl-7-n-propyl-3/7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, d_i hydrochloride: and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(l-benzylpiperidyl-4-aminosulfonyl)pheny

1]-5-methyl-7-n-propyl-3, 7-dihydropyrrolo[2, 3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl~5-(2-(piperidin-1-yl)ethylamino-1-sulfonyl )phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochlori.de
and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-benzylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-phenylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(piperazinyl-1-sulfonyl)phenyl]-5-methyl -7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-benzo[1,3]dioxol—5-yl-methylpiperaz in yl-1-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropy rrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[4-(3-phenyl-n-propan-l-yl)piperidyl-1-sulfonyl]phenyl-5-methyl-7-n-propy1-3, 7-dihydropyrrolo[

2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(n-propylamino-1-sulfonyl)phenyl]-5-meth yl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2- [2-ethoxyl-5-(N,N-di(2-hydroxyethyl)aminosulfonyl)phe nyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[ 2, 3-dJpyrim idin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-methyl]aminosulfon yl}phenyl-5-methyl-7-n-propyl-3/7~dihydropyrroio[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-ethyl]aminosulfony 1}phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-n-butyl]aminosulfo nyl}phenyl-5-methy1-7-n-propyl-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2~ethoxyl-5-(p-ethoxylcarboxylphenylamino)-N-sulfony 1]phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-dJ pyrimidin-4-one, the monohydrochloride, dihydrochloride

and other possible hycirochloride thereof;
2-[2-ethoxyl-5-(o-benzoylphenylamino)-N-sulfonyl]phenyl -5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2- [2-ethoxyl-5- (N2-acethydrazido) -Nl-sulf onyl] phenyl - 5)-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride and dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(2-dimethylaminoethylamino)-N-sulfonyl]p henyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyri midin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -ethyl-7-n-propyl-3/7-dihydropyrrolo[2,3-d]pyrimicin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -morpholinomethyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2~ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 - (pyrimidinyl-2 ) -methyl-7-n-propyl~3, 7-dihydropyrro.lo [2 ,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;

and
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenylJ-5 -methyl-7-allyl-3, 7-clihydropyrrol o [2, 3-d] pyrimidin-4-on e, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof.
The compounds of general formula I can not only be prepared into orally-administrated solid formulations, such as the tablets, pills, capsules and powder, but also liquid ones, such as suspensions, solution, emulsion and syrup. All of these formulations may comprise a variety of conventional excipients, such as the wetting agents, sweet-enhancers, aromatics and preservatives, etc., they may also comprise some other conventional functional excipients, such as the fillers (starch and carbohydrates), binders (carboxymethylcellulose etc.), dispersants (calcium carbonate and sodium carbonate etc. ) , di Luents (glycero 1 ) , absorption enhancers (quaternary ammonium compounds), lubricants (stearate) and absorption agents (kaoi i n) .
The compounds of the formula I can be prepared into ointment, for external use. Likewise, they can be also prepared into intravenous injections.
Generally, for human, oral administration of the compounds of this invention is the preferred route, being the most convenient route and avoiding the disadvantages associated with administration in corpus cavernosum. In circumstances where the patients suffers from a swallowing disorder or

from impairment of drug absorption after oral administration, the drug may be administrated parenterally, e.g. sublingually, buccally, transdermally or injection.
For veterinary use, a compound of formula I or a non-toxic salt thereof is administered as a suitable acceptable formulation in accordance with common veterinary practice and the veterinary surgeon will determine the dose range and route of administration, which wi] 1 be the most appropriate for a particular male animal.
Furthermore, none of any obvious sign of adverse acute toxicity is shown for the compounds of this invention tested in rat and dog, both intravenously (i.v.) and orally (p.o.) at up to 3 mg/Kg. For the situation of mice, no deaths occurred after doses of up to lOOmg/Kg i.v.. The LD Best modes for carrying out the invention
Now, the preparing methods of the compounds of the present invention are further illustrated by the preparation of 2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi]-h -methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride and dihydrochlori.de thereof as example.
Example 1
Preparation ot
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi]

-5-methyl-7-n-propyl~3, 7-dihydropyrrolo[2,3-d]pyrimidin -4-one, its monohydrochloride and dihydrochloride
Route of synthesis

Example 2
Experiments of penis erection
In order to demonstrate efficacy of the compounds of formula I in treatment of functional impotence, the penis erection experiment was established by using the male rabbit as experimental model cross reference to Bischoff's method. (Bischoff E. ; Schneider K, International Journal of Impotence Research, 2 0 01, 13, 2 30-2 35)
The hydrochloride , of
3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one derivatives was
dissolved into water* and injected to conscious-rabbits
intravenously (i.v.) (0.lmg-3mg/kg). Erection was accessed by comparing the length of penis before and at 0, 30, 60, 90 and 120 minutes after intravenous administration of the above-mentioned agents. The results of typica1 compounds in this erectile experiment were listed in table;

the good potential in treatment of functional erectile dysfunction with the characteristics of quick onset and prolonged effectiveness, especially the compoundl-lHCl.
Example 3
Experiments of the effect of single administration on the coitus function of male rats
After purchasing, the male rat and the estrogenized female rat were kept in the same cage for 2 days, and the male rat would acquire the sexual experiences. Then, the female rat was taken out of the cage, and the experiments began after the male rat stayed alone in a cage for 5 days. Each tested compound was orally administered in a dosage of 24mg/kg, the positive group was administered with Sildenafi1 citrate(Viagra) in a dosage of 2 4mg/kg, and the control group was administered with saline at the equal volume
( 0.lml/lOg ) . Fifty minutes after administration, the
tested male rats were placed within a observation container (both the diameter and the height of the container were 2 4cm) , and the male rats adapted the new environment for 5 minutes. After that, two estrogenized female rats were placed into the container. The sexual behavior of the male rats in 20 minutes was observed under the non-interfering condition using Panasonic WVCP410/G monitor, the latent-period of straddle, times of straddle, as well as the latent period of the coitus and times of the coitus. All the
experiments were carried out at 21-24° C, and completed

before 11:00 AM. The comparative results among the compounds of the invention, the blank and the positive control drug Sildenafil citrate were listed in Table 2.
The experimental results showed that all the indexes of sexual function of the rats were obviously enhanced after they were administered with compound 1-HC1, namely, the latent period of straddle and coitus were remarkably shortened, and the times of the coitus was obviously increased. And the effect of the compound 1-HCl was stronger than that of the Sildenafil citrate group, especially, the times of the coitus was much more than that of the positive control group(p
Table 2. Effect of
3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one derivatives on the indexes of sexual function of the male rats (average
valuesistandard deviations)
Groups Number the latent times of the latent. timos of
of rats period of straddle period of the coi t us
straddle the co;i tus
(m i n) (m i n )
saline 17 8. 9 ±3. 6 9 7. 1 ±3.62 1 6.2±4 . 02 3.4 ±4 . 6 4
Compound 1 3 . "1 .1.
9 2 . 6± 1 . 13** 7 . 6±2 . 70 7 . 1 ±5 . 62**
1-HC1 8 . 77*+"
Compound
S 6. 4 ±3. 07 8 . 0±3. 9 3 8. 8 ±5. 8 b* 9.018 . :,0
6-KCJ
Sj Idenaf
11 19 5 . 0 ± 4.74* i 2 . 7 ± 7.18 8 . 2 ± 4 . 02 ** 8 . 7 ± r>. >■! );i-
c :L 1; r a t Q

Compared with the group of saline, *P Example 4
The bioactivity inhibiting phosphodiesterase of compounds of formula I
The bioactivity inhibiting phosphodiesterase 5 (PDES) of compounds of formula 1 was measured cross the reference of methods (Hidaka H, et al Biochirn. Biochim. Biophys. Acta, 1976, 429, 485; Kim D-K, et al. , Bioorg. Med. Chem. 2001, 9, 3013) . The inhibiting activity of PDE5 was deterrni ned using SPA technique and the method of chemical fluorescence. The method was as follows: firstly, the reaction time curve and the enzyme concentration curve of PDES reaction system were determined by Microplate Scintillation & Luminescence-Counter (TopCount Counter) , by which the optimal reaction condition was determined. Under the optimized conditions, the inhibition experiments on PDES were carried out.The results showed that compound I had stronger inhibiting rate on phosphodiesterase 5 than that of sildenafil. For example, when the concentration of compound 1-HC1 was 10~Bmol/L, the inhibiting rate of compound 1-HC1 on PDES was 65.62%, but the inhibiting rate of sildenaf11 on PDE5 was 31.67% .

We claim:
l.A compound of the general formula 1 :

wherein R1 is H; Ci~C4 branched or straight chain alkyl; C| -C4 halogenated branched or straight chain alkyl; C2~C6 alkenyi ; C2-C4 alkynyl; pyridyl, pyrimidinyl,imidazolyl; except H, the above substituents may be optionally substituted with one or more following groups: halogen, cyano, nitro, hydroxyl, carboxyl, guanidino, C.1-C4 alkyl, C1-C4 alkoxyl, C1-C4 alkanoyl, C3-O, cycloalkyi, substituted phenyl, substituted heterocyclic group, CONR'R6, NR-R", CO?R7, NHSO2RH or SO2NR9R10;
R": is H; Cj_-C3 branched or straight chain alkyl; C]~-C R3 is H; C]-C6 branched or straight chain alkyl which may

be optionally substituted with C3-C^ cycloalkyl or C1-C4 alkoxyl; C2^C4 alkenyl; C2^C4 alkynyl;
R is H; Ci~C6 branched or straight chain alkyl which may be optionally substituted with C3-C6 cycloalkyl or C]^C4 alkoxyl; C2~C4 alkenyl; C2~C4 alkynyl;
RJ is H; C1-C4 branched or straight chain alkyl which may
be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO?RM;
C2-C4 alkenyl which may be optionally substituted wit.}) CN,CONR6R7 or CO2R8; C2-C4 alkoxyl optionally substituted with NR6R7; (C2-C3 alkoxyl) C1-C2 branched or straight chain alkyl optionally substituted with OH or NR6R7; CONR6R7; CO2RH; halogen; NRflR7; NHSO2NR6R7; NHSO2R9; SO2NRl0Rri; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazoiyl, thienyl, or triazolyl, either of which is optionally substituted with methyl;
R6 and R; are each independently H or C1-C4 branched or straight chain alkyl; or R6 and R; together with thei r attached nitrogen atom form pyrrolinyl, piperidyl, morpholinyl, 4-N(R12)-piperazinyl or imidazolyl, either of which is optionally substituted with methyl or hydroxyl;
R8 is H; Ci^Cfi branched or straight chain alkyl optionally substituted with C1-C4 alkoxyl, C1-C4 alkylamino, dialkylamino; substituted phenyl and substituted, heterocyclic group in which the substitut(s) on the ring of substituted phenyl and substituted heterocyclic group are defined as the above;

R9 is C1-C3 alkyl optionally substituted with NR6R7;
R10 and R11 are each independently H or Cj-C12 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C2~C6 alkenyl; C2^C6 alkynyl or C3-C6 cycloalkyl; or R10 and R!1 take together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4-N (R13) -piperazinyl; or R10 and Rl1 together with their attached nitrogen atom form a pyrrolinyl, pyrrol inone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl which are optionally substituted with OH, CN, CO2Rb, Ci~C4 branched or straight chain alkyl, Ci~C3 alkoxyl, NRI4RLS or CONR^R1'1; substituted phenyl, substituted heterocyclic group, or C[-C6 branched or straight chain alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are optionally further substituted with OH, CO2R8, NRJVb, CONR14RJ5, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl group;
R12 is H; Ci^Cebranched or straight chain alkyl which may be optionally substituted with phenyl, C?~Ci alkyl substituted by hydroxyi, or C^Q alkoxyl; Ct ~C3 fluoroalkyl; C2-Cf, alkenyl; C2^C6 alkynyl; or C3-C6 cycloalkyl; R1 'is H; CJ-CG branched or straight chain alkyl; C2^C6 branched or straight chain alkyl substituted with C1-C3 alkoxyl; C2-C;, branched or straight chain alkyl substituted with hydroxy L ; C2--C^ branched or straight chain alkyl substituted with NR'4RJi|; C2-C6 branched or straight chain alkyl substituted

with phenyl; Ci^Cg branched or straight chain aikyi substituted with CONR14R15; C-2^C6 branched or straight chain hydrocarbyl substituted with CO2R8; C2-C6 branched or straight chain hydrocarbyl having substituted phenyl or substituted heterocyclic group as substituent; CO-R8, CONRMR15, CSNRI4R15 or C (NH) NR14R15; C^^ halogenated branched or straight chain alkyl; C2~C6 alkenyl; Co^C*. alkynyl or C3-C6 cylcloalkyl; or polyethylene glycol group (n=2~20) , which is optionally substituted with C.^Cs alkyl on its terminal;
RJ4 and Rlb are each independently H; Ci~C4 branched or straight chain alkyl; C2-C4 branched or straight chain alkyl substituted with C3/-C3 alkoxyl; or C2-C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl; and
the substituted phenyl refers to a phenyl which i s substituted with one or more groups selected from Cj -C,-i alkoxyl, halogen, cyano-, CF3/ OCF3, C1-C4 branched or straight chain alkyl on the phenyi ring; The substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxides thereof; pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituting groups on the heterocyclic ring are CL-C; branched or straight chain alkyl, C1-C4 alkoxyl, ami no, as

well as C]~C4 branched or straight chain alkyl amino, Cj-C/j alkoxylamino group;
Or their pharmaceutically acceptable salts.
2.The compound according to claim 1,wherein:R1 is Ci -C . branched or straight chain alkyl optionally substituted with one or more groups selected from a group consisted of the following: C-j^C4 alkyl, Ci~C4 alkoxyl, C]-~C4 alkanoyl, substituted phenyl, substituted heterocyclic group, CONR6R7 and NR6R7;
R" is H; C1-C3 branched or straight chain alkyl optionally substituted with one or more groups selected from a group consisted of the following: substituted phenyl, substituted heterocyclic group, CONR6R;, and NRbR;;
R is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C3-C4 cycloalkyl, CL^C'.: alkoxyl; C2~C4 alkenyl; or C2-C4 alkynyl;
R':1 is H; CJ.-C4 branched or straight chain alkyl which may be optionally substituted with C3-C5 cycloalkyl or Cj -C:: alkoxyl; C-^C4 alkenyl; or C2^C4 alkynyl;
RLl is H; C]-C4 branched or straight chain alkyl which may be optionally substituted with OH, NR6R7, CN, CONR6R7 or CO:!RS ; C2-C4 alkoxyl optionally substituted with NR6R7; NRf'Rv; NHSO-NR6R7; NHSO2R9; SO2NR10Rn; or phenyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, thiazoiyl, thienyl or

triazolyl, either of which is optionally substituted with methyl;
R3 and R are each independently H; C1-C4 branched or straight chain alkyl, or R and R together with their attached nitrogen atom form a pyrrolinyl, piperidyl, morpholinyl, 4-N (R '■) -piperazinyl or imidazolyl, either of which Is optionally substituted with methyl and hydroxyl;
R5 is H or C1-C4 branched or straight chain alkyl; R9 is C.1.-C3 alkyl optionally substituted with NR6R7;
R""" and RlL are each independently H or Ci~Ci2 branched or straight chain alkyl; C1-C3 halogenated branched or straight chain alkyl; C2~C6 alkenyl; C-^CG alkynyl or Cr^C,, cylcoalkyl; or R10 and R11 taken together to form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, 4~N (R13)-piperazinyl; or R10 and Ru together with their attached nitrogen atom form a pyrrolinyl, pyrrolidone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl; the said groups are optionally substituted with OH,CN, CO2RH, CJ^C^I branched or straight chain alkyl, C1/-C3 alkoxyl, NR R1 ', or CONR^R15; substituted phenyl, substituted heterocyclic group, or C]-C6 branched or straight alkyl substituted with substituted phenyl or substituted heterocyclic group, the said groups are further substituted with OH, CO;^RJ, NR *'R ", CONRi4R15, or linked together with another substituted phenyl or substituted heterocyclic group by a ca rbonyl group;

R ^ is H; C_i-C6 branched or straight chain alkyl which may be optionally substituted with C2-C3 alkyl or Ci^C^ alkoxyl, the said alkyl and alkoxyl are substituted with phenyl, hydroxyl; C2~C6 alkenyl or C3-C6 cylcoalkyl;
R13 is H; Ci~C6 branched or straight chain alkyl; C?^Cf-( branched or straight chain alkyl substituted with Ci -C_ R14 and RL5 are each independently H; C.i^C^ branched or straight chain alkyl; Co^-C^ branched or straight chain al kyl substituted with C1-C3 alkoxyl; or C2^C4 branched or straight chain alkyl substituted with hydroxyl; or R14 and R"! ' together with their attached nitrogen atom form pyrrolinyl, pyrrolinone group, piperidyl, or morpholinyl;
The substituted phenyl refers to a phenyl group which is substituted with one or more groups selected from Cj_~C; alkoxyl, halogen, CN, CF3, OCF3, or C.1-C4 branched 01: straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms, and the oxide thereof; or pentatomic rings

containing two or three hetero-atom selected a group consisted of nitrogen, oxygen and sulfur atoms; the substituents on the heterocyclic ring are C^C^ branched or straight chain alkyl, Ci~C4 alkoxyl, amino, as well as Ci~C4 branched or straight chain alkyl amino, C1-C4 alkoxylamino.
3.The compound according to claim 1 or 2, wherein:
RJ is C2~C3 branched or straight chain alkyl which may be optionally substituted with one or more groups selected from substituted heterocyclic group and NR6R ;
R2 is H;
R3 is H; C2^C4 branched or straight chain alkyl which may be optionally substituted with C3-C4 cycloalkyl; CS-C,i alkenyl; C?_^C^ alkynyl;
R4 is C2~C4 branched or straight chain alkyl, which may be optionally substituted with Ci~C3 alkoxyl; C0-C4 alkenyl; C2-C4 alkynyl;
R5 is SO,?NRJ0R]1;
R6 and R; together with their attached nitrogen atom form a pyrrolinyl, piperidyl or morpholinyl;
R8 is H or Ci~C4 branched or straight chain alkyl;
R10 and RJ l are each independently H or C\.'-C]2 branched or straight chain alkyl; C3-C6 cylcoalkyl; or R10 and RJ' take together to forma pyrrolinyl, pyrrolinone group, piper.idyl,

morpholinyl, 4-N (R13) -piperazinyl; or R10 and R11 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl, morpholinyl, or 4-N (R )-piperazinyl; the said groups are optionally substituted with OH,C]_~C4 branched or straight chain alkyl, C^C-3 alkoxyl, NR14R15, or CONR14Rif); substituted phenyl, substituted heterocyclic group, or Ci~Ce branched or straight alkyl optionally substituted with substituted phenyl, substituted heterocyclic group, the said groups are further substituted with OH, CO2R8, NR14RJb or CONR13R1/1, or linked together with another substituted phenyl or substituted heterocyclic group by a carbonyl;
RiJ is H; C1-C3 branched or straight chain alkyl; C?-C{ branched or straight chain alkyl substituted with Cj~C} alkoxyl; C^^C.s branched or straight chain alkyl substituted with OH; Co^-Ce branched or straight chain alkyl substituted with NRL4R15; C2^C3 branched or straight chain a] kyl substituted with phenyl; Ci^Cs branched or straight chain alkyl substituted with CONR14R15; CO2R8 or CONR14R15';
R34 and R1" are each independently H; C1-C4 branched or straight chain alkyl; C2^C4 branched or straight chain alkyl substituted with C1-C3 alkoxyl; or C2-C4 branched or straight chain alkyl substituted with OH; or R1A and R15 together with their attached nitrogen atom form a pyrrolinyl, pyrrolinone group, piperidyl or morpholinyl;
the substituted phenyl refers to a phenyl group which is

substituted with one or more substituents selected from a group consisted of Ci~C4 alkoxyl, halogen, CN, CF3, OCF-U and C1-C4branched or straight chain alkyl; the substituted heterocyclic group refers to hexatomic rings containing one or two nitrogen atoms and the oxide thereof; or pentatomic rings containing two or three hetero-atom selected a group consisted of nitrogen, oxygen, and sulfur atoms; the substituents on the heterocyclic ring are C-i ~C/j branched or straight chain alkyl, C1-C4 alkoxyl, amino, as well as C1-C4 branched or straight chain alkyl amino, Ci -C 4 . The compound according to any one of claims 1-3, wherein the compound is selected from a group consisting of:
2- [2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi]-5
-methyl-7-
n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the
monohydrochloride, dihydrochloride and other possible
hydrochloride thereof;
2-[2-methoxyl-5~(4-ethylpiperazinyl-l-sulfonyl)phenyj.-5-methyl-7-n-propyl-3,7-dihydropyrrolo\2,3-d]pyrimidin-4-one, and the hydrochloride thereof;
2-[2-n-propoxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenyi] -5~methyl-7-n-propyl~3,7-dihydropyrrolo[2, 3-d]pyrimidin -4-one, and the hydrochloride thereof;
2~ [2-ally.loxy-5- (4-ethylpiperazinyl-l-sulf onyl) phenyi] -5-methyl-7-n-propyi-3, 7-dihydropyrrolo [2, 3-d] pyrimid.i n-

4-one, and the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-n~propoxy-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl.} -5-ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-methylpiperazinyl-l-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidi n-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-methylpiperazinyl-l-sulfonyl)phenylJ-5-ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4 -one, the monohydrochloride, dihydrochloride and other-possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-ethoxycarbonylpiperazinyl-l-sulfonyi) phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]py rimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2~[2-ethoxyl-5-(4-(2-hydroxyethyl)piperazinyl-1-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(pyrrolidinyl-1-sulfonyl)phenyl]-5-me thy 1-7-n- propy1-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible

hydrochloride thereof;
2-{2-ethoxyl-5-[3-(2-oxy-pyrrolidin-l-yl)-n-propylamino -N-sulfonyl]phenyl}-5-methyl-7-n-propyl-3, 7~dihydropyrr olo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[2-(pyrrolidin-1-yl)-ethylamino-N-sulfon yl]phenyl}-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(morpholino-4-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(3-(morpholin-4-yl)-n-propylamino-N-suli onyl)phenyl]-5-methyl-7-n-propyl-3/ 7-dihydropyrrolo[2,3 -d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(2-(morpholin-4-yl)-ethylamino-N-sulfony 1)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(2,6-dimethylmorpholino-N-sulfonyl)pheny 1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;

2-[2-ethoxyl-5-(l-benzylpiperidyl-4-aminosulfonyl)pheny 1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimid in-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2- [2-ethoxyl-5- (2- (piperidin-1-yl) ethylamino-1-sulf oriyl )pheny1]-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2~[2-ethoxyl-5-(4-benzylpiperazinyl-l-sulfonyl)phenyJ. ]-5-methyl-7-n-prGpyl~3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-f2-ethoxyl-5-(4-phenylpiperazinyl-l-sulfonyl)pheny1}-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4~one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(piperazinyl-1-sulfonyl)pheny1]-5-methyl -7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-benzo[1,3]dioxol—5-yl-methylpiperazin yl-1-sulfonyl)phenyl]-5-methyl-7-n-propyl-3, 7-dihydropy rrolo[2,3-d] pyrimidin~4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[4-(3-phenyl-n-propan-1-y1)piperidyl-1-s

ulfonyl]phenyl}-5-methyl-7~n-propyl-3,7-dihydropyrrolo f 2, 3-d]pyrimidin~4~one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(n-propylamino-l~sulfonyl)phenyl]-5-meth yl-7-n-propyl-3,7-dihydropyrrolo[2, 3-d]pyrimidin-4-one,
the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2~ethoxyl-5-[N,N-di(2-hydroxyethyl)aminosulfonyl]phe nyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2, 3~d]pyrimi din-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-methyl]aminosulfon yl}phenyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2,3-d] pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-ethyl]aminosulfony 1}phenyl-5-methyl~7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-{2-ethoxyl-5-[N-(2-hydroxyethyl)-N-n-butyl]aminosulfo nyl}phenyl-5-methyl-7-n-propy1-3,7-dihydropyrrolo[2,3-d ]pyrimidin-4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(p-ethoxylcarboxylphenylamino)-N-sulfony 1]phenyl-5-methyl~7-n-propyl-3,7-dihydropyrrolo f2,3-d]p

yrimidin-4-one, the monohydrochloride, dihydrochloride
and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(o-benzoylphenylamino)-N-sulfonyl]phenyl -5-methyl-7~n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin -4-one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(N2-acethydrazido)-Nl-sulfonyl]phenyl-5-methyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-one, the monohydrochloride and dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl~5-(2-dimethylaminoethylamino)-N-sulfony]Jp henyl-5-methyl-7-n-propyl-3f 7-dihydropyrrolo[2,3-d]pyri midin-4-one, the monohydrochloride, dihydrochJ oride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyJ J-5 -ethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]pyrimidin-4-onef the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2~[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -morpholinomethyl-7-n-propyl-3,7-dihydropyrrolo[2,3-d]p yrimidin-4~ one, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof;
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-b -(pyrimidinyl-2)-methyl-7-n-propyl-3r7-dihydropyrrolo [2 ,3-d]pyrimidin-4-one, the monohydrochloride,

dihydrochloride and other possible hydrochloride thereof; and
2-[2-ethoxyl-5-(4-ethylpiperazinyl-l-sulfonyl)phenyl]-5 -methyl-7-allyl-3,7-dihydropyrrolo[2 , 3-d]pyrimidin-4-on e, the monohydrochloride, dihydrochloride and other possible hydrochloride thereof.
5. A process for preparing the compounds of general formula I according to claim 1, comprising:
compound IE is reacted with compound IF:

in an inert solvent in the presence of an organic base as
a catalyst as well as acid neutralizer at -2 0°C to 8CTC,
wherein R1, R2, R3, R4 and R5 are defined as claim 1, to obtain compound ID:

wherein R1, R2, R3, R4 and R5 are defined as the above,
then compound IA may be prepared by heating compound ID in an acidic aqueous solution:

IA wherein R1, R2, R3, R4 and R5 are defined as the above,
and then a cyclization reaction of compound IA is carried out by heating and refluxing in an appropriate soluti on under acidic, basic or neutral condition to obtain compound of formula I:
wherein R1, R2, R3, R4 and R5 are defined as the above; or,
compound of formula I is obtained directly by cyclization of the corresponding compound ID under conditions as

follows:
a) heating to 100~300°C in mixture of phosphorus pentoxide,
water and tertiary amine, or,
b) reacting at room temperature or reacting by heating in
basic hydrogen peroxide aqueous solution, or,
c) reacting at room temperature or reacting by heating
under acidic hydrous or anhydrous condition;
or,
specific example of compounds of general formula I wherein R' is SO^NR R~ may be prepared by processes as follows:
compound IC is obtained by reaction between compound IF' and compound IE wherein R5 is H;

wherein R1, R2, R3 and R4 are defined as the above,
then compound IB is obtained by reacting compound IC with ch.lorosulfonic acid alone or in dichloromethane, chloroform, and other inert or polar non-proton solvents,

wherein R1, R2, R- and R4 are as previously defined,
and then acylation reaction occurs between compound IB and proper amines in dichloromethane, chloroform, tertiary amine or other inert or polar non-proton solvents at -78
°C to 100°C to obtain compound of formula I wherein R'1 is SO2NRuRl2, wherein R11 and Rl2 are defined as claim 1;
or, compound IG
wherein R1, R2, R3, R4 and Rs are defined as claim 1, reacts with compound IH in the solvents of polar non-proton solvents in the presence of the base as catalyst to obtain compound of formula I, wherein X represents Cl, Br or 1 , R" is defined as claim 1;

Optionally, compounds of the formula I can be converted into the corresponding salts by reacting with pharmaceuticaily acceptable acids.
6 .A pharmaceutical composition containing the compound according to any one of claims 1-4 as active ingredient, and pharmaceuticaily acceptable excipient.
7.A veterinary drugs composition containing the compound according to any one of claims 1-4 as active ingredient, and veterinarily acceptable excipient.
8. Use of compounds according to any one of claims 1-4 for
the manufacture of a medicament for treatment or prevention
of the diseases related with phospholipase and the function
thereof.
9. The use according to claim 8, wherein the diseases
includes: male sexual (erectile) dysfunction, female
sexual dysfunction, premature delivery, dysmenorrhea,
benign pros tat ic hyperplasia, bladder obstruct; ion,
incontinence, stable or unstable angina, hypertension,
pulmonary hypertension, congestive heart failu re,
arteriosclerosis, stroke, peripheral circulatory disease,
low vascular patency, chronic asthma, allergic asthma,
bronchitis, allergic rhinitis, glaucoma, disorder of the
gastrointestinal movement, forerunner of the sei zure,
Kawasaki disease, tolerance of nitric acid ester, multiple
sclerosis, peripheral nerve syndrome caused by diabetes,
Alzheimer disease (AD), acute respiratory system failure,

psoriasis, skin gangrene, metastasis of cancer cell, .loss of hair, nutcracker esophagus, anal fissure, and hypoxia-induced vasoconstriction.
10.Intermediates IA-IG for the manufacture of compound ot formula I according to claim 1:

Documents:

0001-chenp-2006 abstract duplicate.pdf

0001-chenp-2006 claims duplicate.pdf

0001-chenp-2006 description(complete) duplicate.pdf

0001-chenp-2006-abstract.pdf

0001-chenp-2006-claims.pdf

0001-chenp-2006-correspondnece-others.pdf

0001-chenp-2006-description(complete).pdf

0001-chenp-2006-form 1.pdf

0001-chenp-2006-form 18.pdf

0001-chenp-2006-form 26.pdf

0001-chenp-2006-form 3.pdf

0001-chenp-2006-form 5.pdf

0001-chenp-2006-pct.pdf

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abs-1.jpg

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Patent Number

231154

Indian Patent Application Number

1/CHENP/2006

PG Journal Number

13/2009

Publication Date

27-Mar-2009

Grant Date

03-Mar-2009

Date of Filing

02-Jan-2006

Name of Patentee

TIANJIN TASLY GROUP CO., LTD.

Applicant Address

No. 1, Liaohe Dong Road, Beichen Hi-Tech Park, Beichen District, Tianjin 300 402,

Inventors:

#	Inventor's Name	Inventor's Address
1	WANG, Yongfeng	C 35, Third Floor, No. 7, Kaihua Road, Huayuan Sci-Tech Industry Garden, Tianjin 300 384,
2	ZHAO, Kejun	No. 32 Zhujiang Road, Yantai Economic Development Area, Shandong 264 006,

PCT International Classification Number

C07C51/00

PCT International Application Number

PCT/CN2004/000487

PCT International Filing date

2004-05-14

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	03142399.X	2003-06-06	China