Title of Invention	COMPOUNDS THAT INHIBIT THE BINDING OF SDF-1OR1-TAC TO THE CHEMOKINE RECEPTOR CCXCKR2
Abstract	A modulator of the structure (i), or a salt thereof: wherein in which the substituents are as described in the description.

Full Text

INHIBITORS OF HUMAN TUMOR-EXPRESSED CCXCKR2 RELATED APPLICATIONS [001] This application claims priority to U.S. provisional application Serial No. 60/434,912 filed December 20, 2002 and U.S. provisional application Serial No. 60/516,151 filed October 30, 2003. The disclosures of the priority applications are incorporated by reference herein in their entirety. BACKGROUND [002] The present invention is directed to novel compounds and pharmaceutical compositions that inhibit the binding of the SDF-1 chemokine (also known as the CXCL12 chemokine) or l-TAC (also known as CXCL11) to the chemokine receptor CCXCKR2. These compounds are useful in preventing tumor cell proliferation, tumor formation, and metastasis. [003] Chemokines are a superfamily of small, cytokine-like proteins that induce cytoskeletal rearrangement, firm adhesion to endothelial cells, and directional migration and may also effect cell activation and proliferation. Chemokines act in a coordinated fashion with cell surface proteins to direct the specific homing of various subsets of ceils to specific anatomical sites. [004] Early research efforts by a number of groups have indicated a role for the chemokine receptor CXCR4 in metastasis and tumor growth. Muller, et al., "Involvement of Chemokine Receptors in Breast Cancer Metastasis," Nature, 410:50-56 (2001) demonstrated that breast tumor cells use chemokine-mediated mechanisms, such as those regulating leukocyte trafficking, during the process of metastasis. Tumor cells express a distinct, non-random pattern of functionally active chemokine receptors. Signaling through CXCR4 mediates actin polymerization and pseudopodia formation in breast cancer cells, and induces chemotactic and invasive responses. Additionally, the organs representing the main sites of breast cancer metastasis (such as lymph nodes, bone marrow, and lungs) are the most abundant sources of ligand for the CXCR4 receptor. [005] Using immunodeficient mice, Muller and colleagues succeeded in reducing the metastasis of injected human breast cancer cells by treating mice with an antibody known to bind CXCR4. Their finding suggests that breast cancer metastasis could be reduced by treating a patient with a CXCR4 antagonist. [006] Bertolini, et aL, "CXCR4 Neutralization, a Novel Therapeutic Approach for Non-Hodgkin's Lymphoma," Cancer Research, 62:3106-3112 (2002) demonstrated a reduction of tumor volume as well as prolonged survival of immunodeficient mice injected with human lymphoma ceils treated with anti-CXCR4 antibodies. They interpreted their finding to mean that tumor volume could be reduced by treating a patient with a CXCR4 antagonist. [007] More recent studies suggest that another chemokine receptor, CCXCKR2, may also be a potential candidate in the treatment of cancer. CCXCKR2 is preferentially expressed in transformed cells over normal cells, with detectable expression in a number of human cancers. In vitro studies indicate that proliferation of CCXCKR2 expressing cells can be inhibited by an antagonist of CCXCKR2. In vivo studies in mice indicate that CCXCKR2 antagonists can inhibit tumor formation and tumor growth. [008] The potential importance of CCXCKR2 is illustrated by an alternative interpretation of the reduction in tumor volume seen by Bertolini and colleagues. This reduction-could clearly be the result of an antibody-mediated clearance, and not the result of thp anti-OXCR4 pntihnHv ** originally believed. In an antibody-mediated clearance, any antibody that recognized a protein on the cell surface of the lymphoma cells would have had the same effect as that attributed to the anti-CXCR4 antibody. Unfortunately, Bertolini and colleagues studies are inconclusive as to whether the observed tumor response was due to antibody-mediated clearance or interaction with CXCR4. [009] However it is now known that the lymphoma cells used by Bertolini and colleagues express both CXCR4 and CCXCKR2. SDF-1 is the only ligand for CXCR4. SDF-1 and l-TAC both bind CCXCKR2. Using anti-SDF-1 antibody, it has now been shown that antagonists of CCXCKR2 are responsible for the reduction in tumor load and increased survival rate. Because SDF-1 is the only ligand for CXCR4, one would expect neutralization of SDF-1 with anti-SDF-1 antibody would be equivalent to the neutralization of CXCR4 with anti-CXCR4 antibody. However, experiments using an anti-SDF-1 antibody demonstrated only a partial reduction in tumor load and an increased survival rate. This leads one to believe-that CCXCKR2 is the actual target, as the continued activity is likely due to the interactions of the second ligand, l-TAC, with CCXCKR2. [0010] Until recently, the possible importance of CCXCKR2 in tumor cell proliferation, tumor growth, and metastasis was unknown. Now, with recent evidence pointing to the ability of certain CCXCKR2 antagonists to prevent the growth and spread of cancer, and expression patterns indicating a limited tissue distribution for the CCXCKR2 receptor, it would be beneficial to provide compounds that are able to bind specifically to the CCXCKR2 receptor on tumor cells with potentially few side effects. SUMMARY [0011] The present invention is directed to novel compounds and compositions containing small molecule modulators that bind to the [0015] In another embodiment, a method of treating cancer is disclosed. [0016] These and other embodiments are discussed more fully below. DETAILED DESCRIPTION [0017] The present invention provides compositions that include a pharmaceutical^ acceptable carrier and an active compound that modulates the binding of SDF-1 and/or l-TAC chemokines to the CCXCKR2 receptor expressed by cancer cells. Preferably, these active compounds bind to the CCXCKR2 receptor on tumor cells, but do not appreciably bind with lymphoid-derived cells or myeloid cells. The compounds and compositions of the present invention are useful for treating cancer, especially for reducing the incidence of breast cancer metastasis. DEFINITIONS [0018] When describing the compounds, compositions, methods, and processes of the invention, the following terms are defined as follows, unless otherwise indicated. [0019] "Alkoxy" refers to an -OR' group. Representative alkoxy groups include, byway of example, methoxy, ethoxy, isopropyloxy, trifluoromethoxy and difluoromethoxy. [0020] "Alkyl" by itself or as part of another substituent refers to a hydrocarbon group which may be linear, cyclic, or branched or a combination thereof having the number of carbon atoms designated (i.e., C1-8 means one to eight carbon atoms). Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyi, cyclopentyl, (cyclohexyl)methyl, cyclopropylmethyl and the like. Examples of substituted aikyl include haloalkyl, thioalkyl, aminoalkyl, and the like. [0021] "Alkyiene" by itself or as part of another substituent means a divalent radical derived from an alkane, as exemplified by -CH2CH2CH2CH2-. Typically, alkyl (or alkyiene) groups having 8 or fewer carbon atoms are preferred in the present invention. Representative alkyiene groups include, by way of example, methylene, ethane-1,2-diyl ("ethylene"), propane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, and the like. [0022] "Alkenyl" refers to an unsaturated hydrocarbon group which may be linear, cyclic or branched or a combination thereof. Aikeny! groups with 2-10 carbon atoms are preferred. The alkenyl group may contain 1, 2 or 3 carbon-carbon double bonds. Examples of alkenyl groups include ethenyl, n-propenyl, isopropenyi, n-but-2-enyl, n-h.ex-3-enyl and the like. [0023] "Alkynyl" refers to a monovalent unsaturated hydrocarbon group which may be linear, cyclic or branched and which has at least one, and typically 1, 2 or 3, carbon-carbon triple bonds. Unless otherwise defined, such alkynyl groups typically contain from 2 to 10 carbon atoms. Representative alkynyl groups include, by way of example, ethynyl, n-propynyl, n-but-2-ynyl, n-hex-3-ynyl, and the like. [0024] "Aryl" refers to a polyunsaturated, aromatic hydrocarbon group having a single ring (i.e., phenyl) or multiple rings which are fused together (i.e., naphthalene) or linked covalently. Unless otherwise defined, such aryl groups typically contain from 6 to 10 carbon ring atoms. Representative aryl groups include, byway of example, phenyl and naphthalene-1-yl, naphthalene-2-yl, biphenyl and the like. [0025] "Arylene" refers to a divalent aromatic hydrocarbon having a single ring (i.e., phenylene) or fused rings (i.e., naphthalenediyl). Unless otherwise defined, such arylene groups typically contain from 6 to 10 carbon ring atoms. Representative arylene groups include, by way of example, 1,2-phenylene, 1,3-phenylene, 1,4-phenyIene, naphthalene-1,5-diyl, naphthalene-2,7-diyl, and the like. [0026] "Aralkyl" refers to an aryl substituted alkyl group. Representative aralkyl groups include benzyl. [0027] "Compound" refers to a specific molecule and includes its enantiomers, diastereomers, polymorphs and salts thereof. [0028] "Condensation" refers to a reaction in which two or more molecules are covalently joined. Likewise, condensation products are the products formed by the condensation reaction. [0029] "Cycloalkyl" refers to a monovalent saturated carbocyclic hydrocarbon group having a single ring or fused rings. Unless otherwise defined, such cycloalkyl groups typically contain from 3 to 10 carbon atoms. Representative cycloalkyl groups include, by way of example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. [0030] "Halo" or "halogen" refers to fluoro- (-F), chloro- (-CI), bromo- (-Br), andiodo-(-I). [0031] "Heteroatom" refers to nitrogen, oxygen, silicon, or sulfur. [0032] "Heterocyclyl" refers to a saturated or unsaturated non- aromatic group containing at least one heteroatom. "Heteroaryl" refers to an aromatic group containing at least one heteroatom. Each heterocyclyl and heteroaryl can be attached at any available ring carbon or heteroatom. Each heterocyclyl and heteroaryl may have one or more rings. When multiple rings are present, they can be fused together or linked covalently. Each heterocyclyl and heteroaryl must contain at least one heteroatom (typically 1 to 5 heteroatoms) selected from nitrogen, oxygen or sulfur. Preferably, these groups contain 0-3 nitrogen atoms, 0-1 sulfur atoms and 0-1 oxygen atoms. Examples of saturated and unsaturated heterocyclyl groups include pyrrolidine, imidazolidine, pyrazolidine, piperidine, 1,4-dioxane, morpholine, thiomorpholine, piperazine, 3-pyrroline and the like. Examples of unsaturated and aromatic heterocycyl groups include pyrrole, imidazole, thiazole, oxazole, furan, thiophene, triazole, tetrazole, oxadiazole, pyrazole, isoxazole, isothiazole, pyridine, pyrazine, pyridazine, pyrimidine, triazine, indole, benzofuran, benzothiophene, benzimidazole, benzopyrazole, benzthiazole, quinoline, isoquinoline, quinazoline, quinoxaline anci the like. Heterocyclyl and heteroaryl groups can be unsubstituted or substituted. For substituted groups, the substitution may be on a carbon or heteroatom. For example, when the substitution is =0, the resulting group may have either a carbonyl (-C(0)-) or a N-oxide (-N(0»- [0033] Suitable substituents for substituted alkyl, substituted alkenyl, substituted alkynyl and substituted cycloalkyl include -halogen, -OR', -NR'R", -SR\ -SiR'R"R"\ -OC(0)R\ -C(0)R', -C02R\ -CONR'R", -OC(0)NR'R", -NR"C(0)R', -NR'-C(0)NR"R"\ -NR"C(0)2R\ -S(0)R\ -S(0)2R\ -S(0)2NR'R", -NR'S(0)2R\ -CN, oxo (=0 or -O-) and -N02 in a number ranging from zero to (2m'+1), where nV is the total number of carbon atoms in such radical. [0034] Suitable substituents for substituted aryl and substituted heteroaryl include -halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, -OR1, oxo (=0 or -O), -OC(0)R\ -NR'R", -SR\ -R'.-CN, -N02, -C02R', -CONR'R", ^C(0)R\ -OC(0)NR,RM, -NRMC(0)R\ -NRMC(0)2R', -NR'-C(0)NR"R"\ -NH-C(NH2)=NH, - NR'C(NH2)^NH, -NH-C(NH2)=NR\ -S(0)R\ -S(0)2R\ -S(0)2NR'R", -NR'S( 0)2R" and -N3 in a number ranging from zero to the total number of open valences on the aromatic ring system. [0035] Suitable substituents for substituted heterocyclyl include halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, -OR1, oxo (=0 or-O), -OC(0)R\ -NR'R", -SR\ -R\ -CN, -N02l -OC(0)NR'R", -NRX^R*, -NR"C(0)2R\ -NR'-C(0)NR"Rn\ -NH-C(NH2)=NH, -NR'C(NH2)=NH, -NH-C(NH2)=NR\ -S(0)R\ -S(0)2NR'R", -NR'S(0)2R" and -N3 in a number ranging from zero to the total number of open valences on the aromatic ring system. [0036] As used above, R\ R" and Rm each independently refer to a variety of groups including hydrogen, halogen, unsubstituted or substituted Cvs alkyl, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted C2-s alkenyl, unsubstituted or substituted C2.8 alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heterocyclyl. Preferably, R\ R" and R,M independently refer to a variety of groups selected from the group consisting of hydrogen, unsubstituted d-a alkyl, unsubstituted heteroalkyl, unsubstituted aryl, aryl substituted with 1-3 halogens, unsubstituted Crs alkyl, unsubstituted Crsalkoxy, unsubstituted Crsthioalkoxy groups, or unsubstituted aryI-Cr4 alkyl groups. When R' and R" are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 3-, 4-, 5-, 6-, or 7-membered ring (for example, -NR'R" includes 1-pyrrolidinyl and 4-morpholinyl). [0037] Alternatively, two of the substituents on adjacent atoms of the aryl, heteroaryl or heterocycyl ring may optionally be replaced with a substituentof the formula -T-C(0)-(CH2)q-U-I wherein T and U are independently -NR'-, -O-, -CHr- or a single bond, and a is an integer of from 0 to 2. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -A-(CH2)rB-, wherein A and B are independently -CH2-, -O-, -NR'~, -S-, -S(O)-, -S(0)2-, -S(0)oNR'- or a single bond, and r is an integer of from 1 to 3. One of the single bonds of the new ring so formed may optionally be replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -(CH2)s-X-(CH2)r, where s and t are independently integers of from 0 to 3, and X is -O-, -NR\ -S-, -S(O)-, -S(0)2-, or -S(0)2NR\ The substituent R' in -NR'- and -S(0)2NR'- is selected from hydrogen or unsubstituted Cr6 alkyl. [0038] "Pharmaceutical^ acceptable" carrier, diluent, or excipient is a carrier, diluent, or excipient compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. [0039] "Pharmaceutically-acceptable salt" refers to a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically-acceptable inorganic or organic bases and from pharmaceutically-acceptable inorganic or organic acids, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Salts derived from pharmaceutically-acceptable inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, zinc and the like. Salts derived from pharmaceutically-acceptable organic bases include salts of primary, secondary, tertiary and quaternary amines, including substituted amines, cyclic amines, naturally-occurring amines and the like, such as arginine, betaine, caffeine, choline, N,N'-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethyienediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isoprqpyiamine, lysine, methylglucamine, morphoiine; piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine and the like. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Salts derived from pharmaceuticaily-acceptable acids include acetic, ascorbic, benzenesulfonic, benzoic, camphosulfonic, citric, ethanesulfonic, fumaric, gluconic, glucoronic, glutamic, hippuric, hydrobromic, hydrochloric, isethionic, lactic, lactobionic, maleic, malic, mandelic, methanesuifonic, mucic, naphthalenesulfonic, nicotinic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic and the like. [0040] "Salt thereof refers to a compound formed when the hydrogen of an acid is replaced by a cation, such as a metal cation or an organic cation. Preferably, the salt is a pharmaceuticaily-acceptable salt, although this is not required for salts of intermediate compounds which are not intended for administration to a patient. [0041] "Substituted" refers to a group that is bonded to a parent molecule or group. Thus, a benzene ring having a methyl substituent is a methyl-substituted benzene. Similarly, a benzene ring having 5 hydrogen substituents would be an unsubstituted phenyl group when bonded to a parent molecule. [0042] "Therapeutically effective amount" refers to an amount of a compound, material, or composition including a compound of the present invention that is effective for producing a desired therapeutic effect by treating cancer when administered to a patient in need of treatment. [0043] "Treating" or "treatment" refer to the administration of a composition to a patient, such as a mammal (particularly a human or a companion animal), having a disease or medical condition (such as cancer) which includes: (a) ameliorating the disease or medical condition, i.e., eliminating or causing regression of the disease or medical condition in a patient by preventing the conversion of pre-malignant cancer ceils to their invasive counterparts; (b) suppressing the disease or medical condition, i.e., slowing or arresting the spread of the cancer in a patient; or (c) alleviating the symptoms of the disease or medical condition in a . patient. [0044] "Structure-activity relationship" (SAR) refers to the way in which altering the molecular structure of a compound alters its interaction with a receptor. Modulators [0045] The present invention provides modulators for use in the treatment of cancer. These compounds can serve as modulators of SDF-1 and l-TAC by binding with the CCXCKR2 receptor. Modulators (I) may also serve as modulators against other chemokine receptors. The chemokine family of peptides is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif. Schall (1996) Cytokine 3:165-183; and Oppenheim et al. (1991) Annu. Rev. Immunol. 9:617-648. Chemokines display a range of in vitro and in vivo functions ranging from proinflammatory activities on a range of cell types to proliferative regulatory activities. To date several chemokine receptors have been described. See, for e.g., Neote et al. (1993) Cell 72:415-425; Ponath etal. (1996) J. Exp. Med. 183:2437-2448; and Power etal. (1995) J. Biol. Chem. 270:19495-19500. [0046] in one embodiment, the modulators of the present invention have the general structure (I): where where m is an integer from 1 to 5; each Y is independently selected from the group consisting of hydrogen, halogen, -CN, -N02, -OH, -OR', -C(0)R\ -C02R\ -0(CO)R\ -C(0)NR'R", -OC(0)NR'R", -SR, -SOR, -S02R, -S02NR"R", -NR'R", -NR'C(0)R", -NR'C(0)2R\ -NR'S02R", -NR(CO)NR"R , unsubstituted or substituted Ci-8 alkyl, unsubstituted or substituted C2»8 alkenyl, unsubstituted or substituted C2-s alkynyl, unsubstituted or substituted C3-8 cycloalkyl, unsubstituted or substituted C^io aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl; where each R\ R" and R'n are independently hydrogen, halogen, unsubstituted or substituted Ci_8 alkyl, unsubstituted or substituted C6-10 aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl; Chem. 1990, 55, 2552 and Barney, etal., Tetrahedron Lett. 1990, 31, 5547); sodium triacethoxyborohydride (as described in Abdel-Magid, et al., Tetrahedron Lett. 1990, 31, 5595); sodium borohydride (as described in Gribble; Nutaitis Synthesis. 1987,709); iron pentacarbonyl and alcoholic KOH (as described in Watabane, et al., Tetrahedron Lett. 1974, 1879); and BH3-pyridine (as described in Pelter, et alM J. Chem. Soc, Perkin Trans. 1, 1984,717). [0068] The transformation of intermediate (4) to compound (5) may be carried out in any suitable solvent, such as tetrahydrofuran or dichloromethane, with a suitably substituted acyl chloride in presence of a base. Tertiary amine bases are preferred. Especially preferred bases include triethylamine and Hunnings base. [0069] Alternatively, the transformation of intermediate (4) to compound (5) can also be obtained with a suitable coupling reagent, such as propane phosphonic acid cyclic anhydride, O-(benzotriazol-l-yl)-N,N,N\N'-tetramethyluronium tetrafluoroborate, 1-ethyl-3-(3-dimethylbutylpropyl) carbodiimide or Dicyclohexyl-carbodiimide (as described in B. Neises and W. Stegiich, Angew. Chem., Int. Ed. Engl., 17, 522, 1978), in the presence of a catalyst, such as 4-N,N-dimethylamino-pyridine, or in the presence of hydroxybenzotriazole (as described in K. Horiki, Synth. Commun., 7,251). PHARMACEUTICAL COMPOSITIONS [0070] Pharmaceutical compositions for administration of the claimed active compounds (or salts thereof) may be presented in a dosage unit form and may be prepared by any of the methods known in the art of pharmacy. Preferred methods include the step of combining the active compound, compounds, or salt thereof with one or more carrier that includes one or more accessory ingredient. [0071] In one embodiment, pharmaceutical compositions are prepared by bringing an active compound or salt thereof into association with a liquid carrier, a finely divided solid carrier, or both. If desired, the composition may then be shaped into a product of the desired formulation. In the pharmaceutical composition, the active compound is included in a therapeutically effective amount. * [0072] Pharmaceutical compositions, including, but not limited to pharmaceutically-acceptable salts, containing the active compound may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hardjor. soft capsules, syrups, or elixirs. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents, and preserving agents to provide pharmaceutical^ elegant and palatable preparations. [0073] Tablets contain the active ingredient in admixture with non- toxic pharmaceutical^ acceptable excipients that are suitable for the manufacture of tablets. These excipients may include, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract, and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. The tabtet.may also be coated by the techniques described in U.S. Pat. Nos. 4,256,108; 4,166,452; and 4,265,874 to form osmotic therapeutic tablets for controlled release. [0074] Formulations for oral use may also be hard gelatin capsules, wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, kaolin, or as soft gelatin capsules, wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin, or olive oil. [0075] Aqueous suspensions may also contain the active compositions in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are often referred to as suspending agents, dispersing agents, or wetting agents. Preferable suspending agents include, for example, sodium carboxymethylcellulose, methylcellulose, hydroxy-propylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, and gum acacia. [0076] Preferable dispersing or wetting agents may be a naturally- occurring phosphatide, for example lecithin; condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate; condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol; condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, such as polyoxyethylene sorbitol monooleate; or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example, ethyl or n-propyl p-hydroxybenzoate; one or more coloring agents; one or more flavoring agents; and one or more sweetening agents, such as sucrose or saccharin. [0077] Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, such as arachis oil, olive oil, sesame oil, or coconut oil; or in a mineral oil, such as,liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin, or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid. [0078] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present. [0079] The pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally- occurring gums, such as gum acacia or gum tragacanth; naturally-occurring phosphatides, such as soy bean, lecithin, esters, and partial esters derived from fatty acids; hexitol anhydrides, such as sorbitan monooleate; and condensation products of the said partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents. [0080] Syrups and elixirs may be formulated with sweetening agents, such as glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, flavoring, and coloring agents. [0081] The pharmaceutical compositions of the invention may also be used in combined therapy to modulate chemokine receptor activity and thereby prevent and treat inflammatory and immunoregulatory disorders and diseases, including asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis, AIDS, and atherosclerosis, etc. For example, in the treatment or prevention of inflammation, the present compounds may be used in conjunction with an anti-inflammatory or analgesic agent such as an opiate agonist, a lipoxygenase inhibitor, such as an inhibitor of 5-lipoxygenase, a cyclooxygenase inhibitor, such as a cyclooxygenase-2 inhibitor, an interleukin inhibitor, such as an interleukin-1 inhibitor, an NMDA antagonist, an inhibitor of nitric oxide or an inhibitor of the synthesis of nitric oxide, a non-steroidal anti-inflammatory agent, or a cytokine-suppressing anti-inflammatory agent, for example with a compound such as acetaminophen, aspirin, codene, fentanyi, ibuprofen, indomethacin, ketorolac, morphine, naproxen, phenacetin, piroxicam, a steroidal ... analgesic, sufentanyl, sunlindac, tenidap, and the like. Similarly, the instant compounds may be administered with a pain reliever; a potentiator such as caffeine, an H2-antagonist, simethicone, aluminum or magnesium hydroxide; a decongestant such as phenylephrine, phenylpropanolamine, pseudophedrine, oxymetazoline, epinephrine, naphazoline, xylometazoline, propylhexedrine, or levo-desoxy-ephedrine; an antuitussive such as codeine, hydrocodone, caramiphen, carbetapentane, ordextramethorphan; a diuretic; and a sedating or non-sedating antihistamine. [0082] Compounds of the present invention may be used in combination with other drugs that are used in the treatment /prevention/suppression or amelioration of the diseases or conditions for which compounds of the present invention are useful. Such other drugs may be administered, by a route and in an amount commonly used, contemporaneously or sequentially with a compound of the present invention. When a compound of the present invention is used contemporaneously with one or more other drugs, a pharmaceutical composition containing such other drugs in addition to the compound of the present invention is preferred. Accordingly, the pharmaceutical compositions of the present invention include those that also contain one or more other active ingredients, in addition to a compound of the present invention. [0083] The pharmaceutical compositions may be in the form of an injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents, including those mentioned above. The injectable preparation may also be a sterile, injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1,3-butane diol. Acceptable vehicles and solvents include water,"Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- ordi-glycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. The compositions of the present invention can be injected directly into a solid tumor, into tissue surrounding the solid tumor, or into a blood vessel vascularizing the solid tumor. [0084] The compounds of the present invention may also be administered in the form of suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols. [0085] For topical useT patches, creams, ointments, jellies, solutions, suspensions, and dispersions that contain one or more of the compounds of the present invention may be utilized. Topical application also includes mouth washes and gargles. The pharmaceutical compositions and methods of the present invention may further comprise other therapeutically active compounds that are used in the treatment of cancer. [0086] In the treatment of cancer with the modulators of the present invention, an appropriate dosage level of the antagonist will generally be about 0.01 to 500 mg per kg patient body weight per day, which can be administered in single or multiple doses. Preferably, the dosage level will be about 0.1 to about 250 mg/kg per day; more preferably about 0.5 to about 100 mg/kg per day. A suitable dosage level may be about 0.01 to 250 mg/kg per day, about 0.05 to 100 mg/kg per day, or about 0.1 to 50 mg/kg per day. Within this range the dosage may be 0.05 to 0.5, 0.5 to 5 or 5 to 50 mg/kg per day. [0087] For oral administration, the compositions are preferably provided in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly 1.0, 5.0, 10.0, 15.0, 20.0, 25.0, 50.0, 75.0, 100.0, 150.0, 200.0, 250.0, 300.0, 400.0, 500.0, 600.0, 750.0, 800.0, 900.0, and 1000.0 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated. The compounds may be administered on a regimen that includes 1 to 4 dosages per day, preferably once or twice per day. [0088] It will be understood, however, that the specific dose level and frequency of dosage for any particular patient maybe varied and will depend upon a variety of factors. These factors include the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy. METHODS OF BLOCKING THE CCXCKR2 RECEPTOR [0089] While not wishing to be bound by any particular theory, the compositions of the present invention are believed to provide a method of inhibiting the binding of SDF-1 and/or l-TAC to the CCXCKR2 receptor. SDF-1 is known to provide a target for interfering with the development or spread of cancer cells in a mammal, such as a human. As shown below in examples 24-26, inhibition of the binding of l-TAC to the CCXCKR2 receptor prevents the formation of vascularized tumors. By contacting the compositions described above with a cancer cell that expresses the CCXCKR2 receptor, the invasive response that would otherwise trigger in the cancer cell can be reduced. Accordingly, the present invention is also directed to methods that are useful in the prevention and/or treatment of • cancer, particularly solid tumor cancers, more particularly breast cancer. [0090] As determined by radiolabeled SDF-1 binding and l-TAC displacement, CCXCKR2 was preferentially expressed in human transformed cells. Included in TABLE 2 are those tissue types in which CCXCKR2 was expressed (CCXCKR2*) as well as those tissue types in which CCXCKR2 was not expressed (CCXCKR2"). [0091] In one embodiment, a preferred method of inhibiting the binding of the chemokines SDF-1 and/or l-TAC to a CCXCKR2 receptor includes contacting one or more of the previously mentioned compounds with a cell that expresses the CCXCKR2 receptor for a time sufficient to inhibit the binding of these chemokines to the CCXCKR2 receptor. METHODS OF TREATING CANCER [0092] The present invention also provides a method of treating cancer. A preferred method of treating cancer, includes administering a therapeutically effective amount of one or more of the previously mentioned compounds (or salts thereof) to a cancer patient for a time sufficient to treat the cancer. [0093] For treatment, the compositions of the present invention may be administered by oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous, ICV, intracisternal injection or infusion, subcutaneous injection, or implant), by inhalation spray, nasal, vaginal, rectal, sublingual, or topical routes of administration and may be formulated, alone or together, in suitable dosage unit formulations containing conventional non- toxic pharmaceutical^ acceptable carriers, adjuvants and vehicles appropriate for each route of administration. [0094] In addition to primates, such as humans, a variety of other mammals can be treated according to the method of the present invention. For instance, mammals including, but not limited to, cows, sheep, goats, horses, dogs, cats, guinea pigs, rats or other bovine, ovine, equine, canine, feline, rodent or murine species can be treated. However, the method can also be practiced in other species, such as avian species (e.g., chickens). [0095] Standard in vivo assays demonstrating that the compositions of the present invention are useful for treating cancer include those described in Bertolini, F., et al., Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma. Blood, No. 1, Vol. 96, pp. 282-87 (1 July 2000); Pengnian, L, Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2. Proc. Natl. Acad. Sci. USA, Vol. 95, pp. 8829-34 (July 1998); and Pulaski, B. Cooperativity of Staphylococcal aureus Enterotoxin B Superantigen, Major Histocompatibility Complex Class II, and CD80 for Immunotherapy of Advanced Spontaneous Metastases in a Clinically Relevant Postoperative Mouse Breast Cancer Model. Cancer Research, Vol. 60, pp. 2710-15 (May 15, 2000). [0096] The preceding description does not limit the scope of the invention to the described embodiments, but rather enables a person of ordinary skill in the art of organic chemistry and pharmacology to make and use the invention. Similarly, the examples below are not to be construed as limiting the scope of the appended claims or their equivalents, and are provided solely for illustration. It is to be understood that numerous variations can be made to the compositions and methods below, which lie within the scope of the appended claims and their equivalents. EXAMPLES Example 1: Synthesis of (2-Methyl-3-pheny!-aIlylj-[2-(1-methy[- pyrrolidin-2-yl)-ethyl]-amine: [0097] 0.5 g of 2-(1-methyl-prrolidin-2-yl)-ethylamine (3.89 mmoi) and 0.56 g of 2-methyl-3-phenyl-propenal were combined in 20 ml of anhydrous dichloromethane. The mixture was stirred under nitrogen on 5 g of magnesium sulfate. After two days, thin layer chromatography (TLC) using a 9:1:0.1 dichloromethane/methanol/ammonium hydroxide eluent showed an absence of the starting material. The reaction mixture was filtered, and the collected solid was washed with dichloromethane. The resultant organic layer was then concentrated under vacuum. Ten ml of dry methanol was added to the residual mixture under nitrogen and the solution was cooled to 0"C. To this mixture was added 0.14 g of sodium borohydride. TLC showed an absence of starting material after about 15 minutes. The reaction was then quenched with acetone (1 ml), and the solvent was removed by distillation. The mixture was partitioned between 5 ml of water in chloroform and the layers were separated. The aqueous layer was then extracted 3 times with 30 ml chloroform. The combined organic layer was washed with brine, dried over sodium sulfate, and filtered. Concentration under vacuum gave 0.78 g of a pale yellow solid. Yield: 77%. [0098] LC-MSD, m/z for Ci7H26N2 [M+H]+: 259, [M+2HJ+: 260 [0099] 1H NMR (400 MHz, CDCI3): 5 1.4-1.6 (m, 2H), 1.67-1.82 (m, 3H), 1.9-2.0 (m, 3 H), 2.02-2,20 (m, 2H), 2.38 (s, 3H), 2.58- 2.79 (m, 2, H), 3.02-3.08 (m, 1H), 3.39 (s, 2H), 7.16-7.39 (m, 5H). Example 2: 3,4,5-Trimethoxy-N-(2-methyl-3-phenyl-aIiyI)-N-[2-(1 -methyl-pyrrolidin-2-yl)-ethyl]-benzamide. [00100] 1 -ethyl-3-(3-dimethyiaminopropyl) carbodiimide hydrochloride 0.48 g (2.4 mmol) was added to 20 ml of anhydrous tetrahydrofuran. To this stirred solution, anhydrous triethylamine 0.23 ml (2.4 mmol) was added. After about 15 minutes, 3,4,5 trimethoxy benzoic acid 0.52 g (2.4 mmol) was added. The reaction mixture was stirred for 1 hour under nitrogen at room temperature. Then 1-hydroxybenzotriazoIe 0.24 g (1.76 mmol) was added and after an additional 30 minutes, (2-Methyl-3-phenyl-allyl)-[2-(1-methyl- pyrrolidin-2-yl)-ethyl]-amine 0.42 g (1.6 mmol) was added. After stirring overnight at room temperature, the reaction was quenched with 5 ml of water, and extracted with 20 ml of ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated under vacuum. The mixture was purified by elution from silica gel with 9:1 dichloromethane/methanol to give 0.38 g of a colorless oil. Yield: 53%. [00101] LC-MSD, m/z for C27H36N2O4 [M+H]+: 453.2, [M+2HJ+: 454.2. [00102] 1H NMR (400 MHz, CDCI3): 5 1.44-2.22 (m, 10 H), 2.35 (s, 3H), - 2.92-3.18 (m, 2H), 3.2-3.4 (m, 2H), 3.60-3.66 (m, 1H), 3.8-4.02 (m, 9H), 4.2- -4.4 (m, 2H), 6.45 (s, 1H), 6.63-6.71 (m, 2H), 7.21-7.35 (m, 5H). Example 3: 3,4-Bis-difluoromethoxy-3-methoxy-N-(2-methyl-3-phenyl-alIyl)-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide [00103] A mixture of (2-methyl-3-phenyl-allyl)-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-amine 0.1 g (0.4 mmol) and 3,4-bis-difluoromethoxy-benzoic acid 0.11 g (0.44 mmol) was dissolved in ethyl acetate 20 ml. Triethyl amine 0.16 ml was added to the mixture and stirred at room temperature for 20 minutes. A solution of 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate) 0.25 ml (0.44 mmol) was then added to the mixture, and was stirred overnight at room temperature. A saturated solution of sodium bicarbonate 5 ml was added to the mixture and stirred for 5 min. The layers were separated. The aqueous layer was extracted with ethyl acetate and combined with the organic layer. The organic layer was then dried, concentrated, and subjected to column chromatography on silica gel elution with dichloromethane 9.5:methanol 0.5, yielding the free amine. [00104] The compound was dissolved in dichloromethane and cooled to 0°C under nitrogen atmosphere and was transformed to the HCI salt with HCI- ether solution, yielding 34 mg of a white, hydroscopic compound. Yield: 7%. [00105] LC-MSD, m/z for C26H30F4N2O3 [M+H]+: 495.1 [00106] 1H NMR (400 MHz, CDCI3): 5 1.7 (s, 3 H), 1.9-2.5 (m, 5 H), 2.7- 3.0 (m, 3 H),3.1-3.5 (m, 1 H), 3.3-3.5 (m, 1 H), 3.6-4.0 (m, 6 H), 6.2-6.4 (m, 1 H), 6.5-6.8 (m, 2 H), 7.1-7.5 (m, 8 H). Example 4: 3,4,5-Triethoxy-N-(2-methyl-3-phenyI-al!yI)-N-[2-(1 -methyl-pyrrolidin-2-yI)-ethyl-benzamide. [00107] An analogous procedure to that discussed in Example 2 was used with 3,4,5-triethoxy carboxylic acid 0.22 g (0.8 mmol) and (2-Methyl-3- phenyl-allyl)-[2-(1-methyl-pyrrolidin-2-yl)-ethyI]-amine 0.1 g (0.38 mmol), 1- ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride 0.11 g (0.57 mmol), 1-hydrobenzotriazole 0.05 g (0.418 mmol), and triethylamine 0.08 ml. The resulting product was purified by preparatory high pressure liquid chromatography with a mobile phase gradient including 20% to 80% acetonitrile and 0.1% trifluoroacetic acid in water. 84.3 mg (0.13 mmol) of a white powder was obtained as a TFA salt. Yield: 30%. [00108] LC-MSD, m/z for C3oH42N204 [M+H]+: 495.3, [M+2H]+: 496.3. » .-Example 5: 4-Difluoromethoxy-3-methoxy-N-(2-methyl-3-phenyI-allyI)-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide [00109] Experimental condition analogous to Example 3 were used with (2-Methyl-3-phenyl-allyl)-[2-(1-methyl-pyrrolidin-2-yl)-ethyi]-amine 0.1 g (0.4 mmol), 4-difluoromethoxy-3-methoxy-benzoic acid 0.93 g (0.44 mmol), 1- propanephosphonic acid cyclic anhydride (50% ethyl-acetate) 0.25 ml (0.4 mmol), and triethylamine 0.16 ml. The resulting free amine was transformed to 38 mg of a white, hydroscopic solid as a HCI salt. Yield: 8%. [00110] Analytical C18 HPLC using 20-95% acetonitrile gradient in 20 min, the compound elute at 14.504 minute [00111] LC-MSD, m/z for C26H32N2O3F2 [M+HJ-K 459.1, [M+2H]+: 460.1, [M+3H]: 461.2 Example 6: 3,4-Dimethoxy-N-(2-methyl-3-phenyl-allyl)-N-[2-(1 -methyl-pyrrolidine-2-yI)ethyl]-benzamide [00112] An analogous procedure to that discussed in Example 2 was used with 3, 4-dimethoxycarboxylic acid 0.1 g (0.38 mmol) and (2-methyl-3- phenyl-allylH2-(1-methyi-pyrrolidine-2-yl)-ethyl]-amine 0.1 g (0.38 mmol), 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 0.11 g (0.57 mmol), 1-hydroxybenzotriazole 0.05 g (0.41 mmol) and triethylamine 0.08 ml, to give 179 mg light yellow oil. Yield: 41%. [00113] LC-MSD, m/z for C28H32N2O [M+H]+: 423.2.2, [M+2H]+:424.2 Example 7: 3,5- Dimethoxy-N-(2-methyI-3-phenyl-allyl)-N-[2-(1-methyl-pyrrolidine-2-yl)tethyl]-benzamide [00114] An analogous procedure to that discussed in Example 2 was used with 3,5- dimethoxycarboxylic acid 0.1 g (0.38 mmol) and (2-methyl-3-phenyl-allyl)-[2-(1-methyi-pyrrolidine-2-yl)-ethyl]-amine 0.1 g (0.38 mmol), 1- * ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 0.11 g (0.57 mmol), 1-hydroxybenzotriazole 0.05 g (0.41 mmol) and triethylamine 0.08 ml to give 140 mg of a light yellow oil. Yield: 33%. [00115] LC-MSD, m/z for C26H34N2O3 [M+H]+: 423.2.2, [M+2H]+:424.2 [00116] 1H NMR (400 MHz, CDCI3): 5 1.44-2.00 (m, 14 H), 2.25 (s, 3H), 2.92-3.08 (m, 1H), 3.2 (m, 1H), 3.6 (m, 1H), 3.? (s, 3H), 3.8 (s, 2H), 6.3-6.5 (m, 3H), 7.1-7.4 (m,5H) Example 8: 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxoIe-5-carboxylic acid (2-methyl-3-phenyl-allylH2-(1-methyl-pyrrolidin-2-yl)-ethyl]-amide [00117] An analogous procedure to that discussed in Example 2 was used with 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid 0.07 g (0.3 mmol) and (2-Methyl-3-phenyl-allylH2-(1-methy!-pyrrolidin-2-yl)-ethyl]- amine 0.05 g (0.2 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride 0.56 g (0.28 mmol), 1-hydrobenzotriazole 0.05 g (0.2 mmol), and triethylamine 0.04 ml. The resulting product was purified by preparatory high pressure liquid chromatography with a mobile phase gradient including 20% to 70% acetonitrile and 0.1% trifluoroacetic acid in water. 16.3 mg (0.13 mmol) of white powder was obtained as a HCI salt. Yield: 4%. [00118] Analytical C18 HPLC using 20-95% acetonitrile gradient in 20 min, the compound elute at 15.196 minute [00119] LC-MSD, m/z for C28H36N2O4 [M+H]+: 465.2, [M+2HJ+: 466.2. Example 9: 3,5-Dibromo-N-(2-methy[-3-phenyi-allyI)-N-[2-(1-methyi-pyrrolidin-2-yl)-ethyl]-benzamide [00120] An analogous procedure to Example 2 was used with 3,5-dibromo-benzoic acid 0.16 g (0.38 mmol) and (2-methyl-3-phenyl-allyl)-[2-(1-methyl-pyrrolidine-2-yl)-ethyl]-amine0.1 g (0.38 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 0.11 g (0.57 mmol), 1-hydroxybenzotriazole 0.05 g (0.41 mmol) and triethyiamine 0.08 ml. Reverse phase prep HPLC with a gradient 20-80% for the acetonitrile phase gavel 53 mg as a TFA salt. Yield; 63%. [00121] LC-MSD, m/z for C24H28N20Br2 [M+H]+: 519.3, [M+2H]+: 520.3, [M+3H]+: 521.3, [M+4H]+: 522.3, [M+5H]+: 523.3, [M+6H]+: 524.3 Example 10: 3,5-Dimethyl-N-(2-methyl-3-phenyl-allyl)-N-[2-(1 -methyl-pyrrolidin-2-yI)-ethyl]-benzamide [00122] An analogous procedure to Example 2 was used with 3,5- dimethyl-benzoic acid 0,16 g (0,38 mmol) and (2-methyl-3-phenyl-allyi)-[2-(1- methyl-pyrrolidine-2-yl)-ethyl]-amine0.1 g (0.38 mmol), 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride 0.11 g (0.57 mmol), 1- hydroxybenzotriazole 0.05 g (0.41 mmol) and triethyiamine 0.08 ml. Reverse phase prep HPLC with a gradient 20-80% for the acetonitrile with 0.1% trifiuoroacetic acid phase gave 60 mg as a TFA salt. Yield: 32%. [00123] LC-MSD, m/z for C26H34N2O [M+H]+: 391:5 -[M+2H]+: 392.4 Example 11: 4-Methoxy-3,5-dimethyl-N-(2-methyl-3-phenyI-allyl)-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide [00124] An analogous procedure to Example 2 was used with 4- rnethoxy-3,5-dimethyl-benzoic acid 0.108 g (0.58 mmol) and (2-methyl-3- phenyl-allylH2-(1-methyl-pyrrolidine-2-yI)-ethyl]-amine 0.1 g (0.38 mmol), 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 0.11 g (0.57 mmol), 1-hydroxybenzotriazole 0.05 g (0.41 mmol) and triethylamine 0.08 ml. Reverse phase prep HPLC with a gradient 20-80% for the acetonitrile with 0.1% trifluoroacetic acid phase gave 45.4 mg as a TFA salt. Yield: 22%. [00125] LC-MSD, m/z for C27H36N9O2 [M+H]+: 421.2 [M+2H]+: 422.2 Example 12: 3,4-Dihydro-2H-benzo[b][1,4]dioxepine-7-carboxylic acid(2-methyl-3-phenyl-allyl)-2[-(1-methyl-pyrroIidine-2-yI)-ethyl]-amide [00126] A mixture of (2-methyl-3-phenyl-allylH2-(1-methyl-pyrrolidine-2- yl)-ethyl]-amine 0.1 g (0.38 mmol) and 0.08 ml (0.58 mmol) of triethylamine was stirred in 5 ml anhydrous dichloromethane at 0°C under nitrogen. To this mixture was added 3,4-dihydro-2H-benzo[b][1,4]dioxepine-7-carbonyl chloride 0.098 g (0.456 mmol). To the reaction mixture was added 25 ml of ethyl acetate and 5 ml water. The organic layer was separated from aqueous, then dried with sodium sulfate. The organic layer was filtrated and evaporated under vacuum. Purification using flash chromatography, elution with ethyl acetate 9.5, methanol 0.5 and ammonium hydroxide 0.05, gave a brown oil. t00127] LC-MSD, m/z for 027^^03 fM+Hl+: 435.2, [M+2H]+: 436.2. Example 13: 3,4,5-Trimethoxy-N-(2-methyl-3-phenyl-allyl)-N-(2-pyrrolidin-2-yl-ethyl)-benzamide a: BOC-anhydride, NaOH, acetomtnle, 3 h, RT b: Borane dimethylsulfide, THF, 14 h, RT c: Methanesulfonylchloride, triethylamine, dichloromethane, 4 h, RT d: Sodium cyanide, dimethylfonnamide, 5 h, RT e: Raney nickel, ammonia gas in methanol, H2 2.5 kg pressure, 14 h f: 1/ I-methyl cinnamaldehyde, dichloromethane, 16 h, RT, N2 2/ Sodium borohydride, methanol, 30 minutes at 0°C Scheme 1: Preparation of 2-[2-(2-Methyl~3-phenyl-aUylamino)-etliyl-pyrroIidine-l-carboxyIic acid tert-butyl ester [00128] To a solution of the compound 2-[2-(2-MethyI-3-phenyl-allyIamino)-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (prepared from racemic proline according to the schemel), 0.6 g (2 mmol) and 3,4,5-trimethoxy benzoic acid 0.513 g (2.4mmol) in dry dichloromethane 10ml, triethyl amine 0.2 ml was added and stirred at room temperature for 20 min. Then was added O^benzotriazole-l-yO-N^.N'.N'-tetramethyl uranium tetrafluoroborate 1.3 g (4 mmol) at 0QC. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and was washed with 10% NaHC03 solution, water and brine, dried, concentrated and subjected to column chromatography silica gel using CHCIa/MeOH as eluent to obtain 1 g of 2^2-[(2-Methyl-3-p.henyl-allyl)-3,4]54rimethoxy-benzoyl)-amino]-ethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester. [00129] This compound was dissolved in 10ml of dioxane and 6N HC110 ml was added to it. The reaction mixture was stirred at room temperature for 14 hr, basified with 10% NaOH solution and was extracted twice with ethyl acetate (15 ml). The organic layer was washed with water, brine, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography over silica gel to obtain the free amine 0.35 g. The free amine 100 mg was converted to its hydrochloride salt using dry HCI in ether to yield 88 mg as a white solid. Yield: 39%. [00130] LC-MSD, m/z for C2GH34N204 [M+H]+: 439.3 [00131] 1H NMR (300 MHz, MeOD/D20): 5 1.6-1.8 (m, 4 H), 1.9-2.1 (m, 4H), 2.25 (m, 1H), 3.2 (m, 3H), 3.5-3.8 (m, 12H), 4.1 (s, 2H), 6.5 (s, 1H), 6.7-6.9 (m,2H), 7.2-7.5 (m, 5H) Example 14: N-[2-(1-Benzyl-pyrrolidin-2-yl)-ethyI]-3,4,5-trimethoxy-N-(2-methyl-3-phenyl-aIlyl)-benzamide [00132] 3J4,5-Trimethoxy-N-(2-methyl-3-phenyl-allyl)-N-(2-pyrrolidin-2-yl- ethyl)-benzamide 0.11 g (2.5 mmol) and freshly distilled benzaldehyde 0.026 g (2.5 mmol) was taken in 10ml of dry methanol. Acetic acid 0.022 ml (3.7 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 30 min and sodium cyanoborohydride 0.023 g (3.7 mmol) was added at 0°C. The reaction mixture was gradually warmed to room temperature and stirred for 14 hr. The reaction mixture was concentrated, and the residue was diluted with water and extracted with chloroform (3 x 20 ml). Organic layer was washed with 10% NaHC03 solution, water and brine, dried over anhydrous sodium sulfate, concentrated and the residue was purified by column chromatography over silica gel to yield the pure desired compound. This was converted to its hydrochloride salt using dry HCI in ether to obtain 90 mg of product. Yield: 63%. [00133] LC-MSD, m/z for C33H40N2O4 [M+H]+: 529.3 [00134] 1H NMR (300 MHz, MeOD/D20): 5 1.8-2.2 (m, 10 H), 2.5 (m, 1H), 3.4-3.6 (m, 4H), 3.7 (m, 1H), 3.8 (m, 9H), 4.0 (s, 3H), 4.2-4.5 (m, 2H), 4.7 (d, 1H), 6.25 (s, 1H), 6.8 (s, 2H), 7.2-7.6 (m, 10H). Example 15: N-[2-(1-ethyl-pyrrolidin-2-yl)-ethyl]-3,4,5-trimethoxy-N-(2-methyl-3-phenyl-alIyl)-benzamide [00135] To a solution of 3,4I5-trimethoxy-N-(2-methyl-3-phenyi-al!yi)-N-(2-pyrroiidin-2-yl-ethyl)-benzamide 0.1 g (2.28 mmol) in dry dichloromethane 5 ml, sodium bicarbonate 0.01 g (2.7 mmol) was added followed by ethyl bromide 0.037 g (3.4 mmol) at 0°C. The reaction mixture was stirred at room temperature for 14 hrs. Inorganics were filtered off and filtrate was concentrated. Crude material was subjected to column chromatography on silica gel, elution with chloroform-methanol to yield desired compound as a free amine. This was converted to its hydrochloride salt 42 mg as a yellow semi-solid. [00136] LC-MSD, m/z for C28H38N204 [M+H]+: 467.4 [00137] 1H NMR (300 MHz, MeOD): 5 1.1-2.4 (m, 4 H)T 2.7 (s, 3H), 1.7- 2.1 (m, 4H), 2.4-2.5 (m, 2 H), 3.0-3.2 (m, 2 H), 3.4-3.6 (m, 2 H), 3.6-3.9 (m, 10H), 4.1-4.2 (m, 2 H), 6.4-7.5 (m, 8 H). Example 16: 3, ,5-Trimethoxy-N-(2-methyl-3-phenyl-allyl)-N-(2-(S)-pyrrolidin-2-yI-ethyl)-benzamide a: Borane dimethy (sulfide, THF, 14 h, RT b: MethanesulfonylchJoride, triethylamine, dicliloromethane, 4 h, RT c: Sodium cyanide, dimethylformamide, 5 h, RT d: Raney nickel, ammonia gas in methanol, H2 2.5 kg pressure, 14 h e: 1/ 1 -methyl cinnamaldehyde, dicliloromethane, 16 h, RT, N2 2/ Sodium borohydride, methanol, 30 minutes at 0°C Scheme 2: Preparation of 3*{2-(2-Methyl-3-phenyl-allyIamino)-ethyl-(S)-pynolidine-l-carboxyIic acid tert-butyl ester [00138] Compound 2-[2-(2-Methyl-3-phenyl-allyIamino)-ethyl-(S)- pyrrolidine-1-carboxyIic acidlert-butyi ester (prepared from (S)-Pyrrolidine-1,2-dicarboxyiic acid-1-tert-butyl ester according to the scheme 2) 0.47 .g (1.3 mmol) and 3,4,5-trimethoxy benzoic acid 0.3 g (1.6 mmol) in dry dichloromethane 10ml, triethyl amine.0.1 ml was added and stirred at room temperature for 20 min. Then 1-dimethylaminopropyl-3-ethyl carbodiimide 0.3 g (2 mmol) and 1-hydroxybenzotriazole 0.018 g (0.13 mmol) was added at 0°C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and was washed with 10% sodium bicarbonate solution, water and brine, dried, concentrated and subjected to column chromatography (silica gel, n-hexane: ethyiacetate as eluent) to yield 0.57 g 2-{2-[(2-methyl-3-phenyl-allyl)-3I4,5-trimethoxy-benzoyl)-amino]-ethyl}-(S)-pyrrolidine-1-carboxylic acid tert-butyl ester (Yield: 76%). The compound 0.22 g (0.4 mmol) was dissolved in 5ml of dry ether and 5ml of dry ether saturated with HCI was added at 0°C. The reaction mixture was stirred at room temperature for 10 hrs. The ether was concentrated and the residue was washed with dry ether three to four times to yield 0.12 gas a white solid. Yield: 30%, . ; - . . phenol 0.058 g (0.62 mmol) in 10 mi anhydrous dichloromethane, triphenylphosphine 0.16 g (0.6 mmol) was added followed by diethylazodicarboxylate 0.16 g (0.6 mmol), at 0°C. The reaction mixture was stirred at room temperature for 18 hr\ concentrated and purified by column chromatography over silica gel elution with chloroform and methanol to yield the free amine, which was then converted to the HCI salt, to give 39 mg of a brown semi-solid. Yield: 17%. [00341] LC-MSD, m/z for C34H42N2O5 [M+H]+: 559.3 [00342] 1H NMR (300 MHz, MeOD): 8 1.8-1.9 (m, 3 H), 2.0-2.5 (m, 6 H), 3.4 (m, 2 H), 3.5-4.0 (m, 13 H), 4.0-4.2 (m, 3 H), 4.3-4.5 (m, 2 H), 6.4 (s, 1 H), 6.8 (s, 2 H), 7.0-7.2 (m, 3 H), 7.2-7.5 (m, 7 H). Example 82: N-fS^S-Benzyiamino-piperidin-l-yO-propyQ-S^jS-trimethoxy-N-(2-methyl-3-phenyl-ailyl)-benzamide [00343] 20 ml of anhydrous dichloromethane thethylamine 0.2 ml was added to a solution of N-[3-(3-hydroxy-piperidin-1-yl)-propyl]-3,4,5-tnmrthoxy-N-(2-methyl-3-phenyl-allyl)-benzamide 0.5 g (1.0 mmol). Thereafter, methane sulfonyl chloride 0.14 g (1.2 mmol) at 0°C was added. The reaction mixture was stirred for 6 hr, diluted with dichloromethane, and washed with water and brine, yielding the intermediate chlorine 0.4 g (0.8 mmol) as a brown solid. [00344] To this intermediate chlorine 0.15 g (0.29 mmol) in acetonitriie, potassium carbonate 0.12 g (0.8 mmol) was added and was stirred at room temperature for 40 minutes. To this mixture benzylamine 0.03 g (0.29 mmol) was added and the mixture refluxed at 80°C for 14 hr. Potassium carbonate was filtered off and the filtrate was concentrated. Residue was diluted with chloroform and washed with 1.5 N HCI. Organic layep was dried over anhydrous sodium sulfate, filtrated and concentrated under vacuum. TESTING [00400] To demonstrate that the compounds described above are useful modulators for SDF-1 and l-TAC chemokines, the compounds were screened in vitro to determine their ability to displace SDF-1 and/or l-TAC from the CCXCKR2 receptor at multiple concentrations. The compounds were combined with mammary gland cells expressing the CCXCKR2 receptor in the presence of the 125 i-labeled chemokine as detailed in Determination of !C5o values, Reagents and Cells (see below). The ability of the compounds to displace the labeled chemokine from the CCXCKR2 receptor cites at multiple concentrations was then determined with the screening process. [00401] Compounds that were deemed effective modulators were able to displace at least 50% of either of the chemokines SDF-1 or l-TAC from the CCXCKR2 receptor at concentrations at or below 1.1 micromolar (pM) and more preferably at concentrations at or below 300 nanomolar (nM). At present, especially preferred compounds can displace at least 50% of the SDF-1 or l-TAC from the CCXCKR2 receptor at concentrations at or below 200 nM. Exemplary compounds that met these criteria are reproduced in Table I below. (adenocarcinoma; mammary gland) cell line was obtained from the American Type Culture Collection (Manassas, VA) and was cultured in DMEM (Mediatech, Herndon, VA) supplemented with 10% fetal bovine serum (FBS) (HyClone Logan, UT) and bovine insulin (0.01 mg/mL) (Sigma, St. Louis, MO) at 37° C in a humidified incubator at a 5% C02/air mixture. [00403] Binding Analysis. Target compounds were tested to determine their ability to bind with CCXCKR2 sites on MCF-7 cells. Efficiency-maximized radioligand binding using filtration protocols as described in Dairaghi DJ, et al., HHV8-encoded vMIP-l selectively engages chemokine receptor CCR5. Agonist and antagonist profiles of viral chemokines., J. Biol. Chem. 1999 Jul 30; 274(31): 21569-74 and Gosling J, et al., Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK., J. Immunol. 2000 Mar 15; 164(6):2851-6 was used. [00404] In these assays, MCF-7 cells were interrogated with the target compounds and the ability of these compounds to displace 1251 radiolabeled SDF-1 was assessed using the protocol described in Dairaghi and Gosling. The target compounds were added to the plate to the indicated concentration and were then incubated with cells followed by the addition of radiolabeled chemokine (125l SDF-1) for 3 hr at 4°C in the following binding medium (25 mM HEPES, 140 mM NaCI, 1 mM CaCI2, 5 mM MgCI2 and 0.2% bovine serum albumin, adjusted to pH 7.1). All assays were then incubated for 3 hrs at 4° C with gentle agitation. Following incubation in all binding assays, reactions were aspirated onto PEI-treated GF/B glass filters (Packard) using a cell harvester (Packard) and washed twice (25 mM HEPES, 500 mM NaCI, 1 mM CaCI2, 5 mM - MgCI2, adjusted to pH 7.1). "Scintillant (MicroScint 10, Packard) was added to the wells, and the filters were counted in a Packard Topcount scintillation counter. Data were analyzed and plotted using Prism (GraphPad Prism version 3.0a for Macintosh, GraphPad Software, www.graphpad.com). Inhibition of cell proliferation in vitro. [00405] Antagonism of CCXCKR2 expressed on a mammary carcinoma by small molecular weight compounds inhibited cell proliferation in vitro. Cells treated in vitro exhibited reduced cell growth over time as compared to untreated controls. Inhibition of cell adhesion in vitro. [00406] In vitro static adhesion assays are used to model the events of leukocyte migration, including the adhesion of cells and subsequent emigration into a given tissue. Monolayers of vascular endothelial cells were grown on a surface, and cells expressing CCXCKR2 were labeled with a fluorescent dye to enable visualization. Experiments showed that the presence of CCXCKR2 expressing cells adhered to an endothelial layer encouraged adhesion of additional CCXCKR2 expressing cells as compared to control groups in which CCXCKR2 was not expressed. Additionally, the addition of a CCXCKR2 modulator inhibited adhesion as compared to a vehicle-treated control group. Inhibition of tumor formation in vivo. [00407] Immunodeficient mice were injected with human B cell lymphoma cells expressing CCXCKR2. Treatment of those mice with CCXCKR2 modulators inhibited the ability of vascularized tumors to form. In one study, only one of 17 mice treated with a CCXCKR2 antagonist developed an encapsulated, vascularized tumor, while 11 of 17 mice in a vehicle control group developed encapsulated, vascularized tumor. Reduction of tumor volume in vivo. [00408] Immunodeficient mice were injected with a human mammary carcinoma. Tumor measurements were made three times a week and tumor volume was determined. Mice treated with a CCXCKR2 modulator exhibited reduced tumor volumes as compared to mice in the vehicle control group. [00409] Any person of ordinary skill in the art of organic chemistry will recognize from the provided description, figures, and examples, that modifications and changes can be made to the preferred embodiments of the invention without departing from the scope of the invention defined by the following claims and their equivalents. WHAT IS CLAIMED IS: 1. A modulator of the structure (I), or a salt thereof: where m is an integer from 1 to 5; each Y is independently selected from the group consisting of hydrogen, halogen, -CN, -N02, -OH, -OR', -C(0)R\ -C02R\ -0(CO)R\ -C(0)NR'R]\ -OC(0)NRR", -SR, -SOR, -S02R, -S02NR'R", -NR'R", -NR'C(0)R'\ -NR'C(0)2R\ -NRS02R", -' NR(CO)NR~R", unsubstituted or substituted CVs alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2.8 alkynyl, unsubstituted or substituted C3_8 cycloalkyi, unsubstituted or substituted C6-10 aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl; where each R\ R" and R'" are independently hydrogen, halogen, unsubstituted or substituted Ci.8 alkyl, unsubstituted or substituted C6-io aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl; nisO, 1,2 or 3; Z is -CHR1R2- -OR1, or-NR1R2; R1 and R2 are each independently substituted or unsubstituted alkyl or hydrogen, or Z in combination with R1 and R2form a substituted The modulator of claim 1, where R7 is substituted or unsubstituted CHO alkyl, substituted or unsubstituted C^o alkoxy , substituted or unsubstituted aryloxy, or substituted or unsubstituted C3-10cycIoalkyl. 21. The modulator of claim 1, where n is 1, 2, or 3. 22. The modulator of claim 1, where m is 1 or 2, and each Y is a halogen. 23. The modulator of claim 1, where m is 0. 24. The modulator of claim 1, where substituted alkyl, substituted alkenyl, substituted alkynyl and substituted cycloalkyl can each independently be substituted 1 to 3 times with halogen, -OR', -NR'R", -SR\ -SiR'R"R"\ OC(0)R\ -C(0)R\ :C02R\ -CONR'R", -OC(0)NR'R", -NR"C(0)R\ -NR'-C(0)NRMR"\ -NR"C(0)2R\ -S(0)R\ -S(0)2R\ -S(0)2NR'R", -NR'S(0)2R", -CN, oxo (=0 or -0-) or -N02, where R\ R" and R"' each independently hydrogen, halogen, unsubstituted C1-8 alkyl, unsubstituted C3-6 cycloalkyl, unsubstituted C2-8 alkenyl, unsubstituted or C2-8 alkynyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted or substituted heterocyclyl. 25. The modulator of claim 1, where substituted aryl and substituted heteroaryl can each independently be substituted 1 to 3 times with halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, -OR', oxo (=0 or -0), -OC(0)R\ -NR'R", -SR\ -R\ -CN, -N02, -C02R\ -CONR'R", -C(0)R\ -OC(0)NR,R"1 -NR*C(0)R\ -NRnC(0)2R\ -NR'-C(0)NRMRn\ -NH-C(NH2)=NH, - NR'C(NH2)=NH, -NH-C(NH2)=NR\ -S(0)R\ -S(0)2R\ -SCO^NR'R", -NR'S( 0)2R" and -N3, where R\ R" and R"' each independently hydrogen, halogen, unsubstituted C^alkyl, unsubstituted C3.6 cycloalkyl, unsubstituted C2.8 alkenyl, unsubstituted C2.8 alkynyl, unsubstituted or substituted aryl, unsubstituted heteroaryl, unsubstituted heterocyclyl. 26. The modulator of claim 1, where substituted heterocyclyl can be substituted 1 to 3 times with halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, -OR', oxo (=0 or -O), -OC(0)R\ - NR'R", -SR', -R\ -CN, -N02l -OC(0)NR'R", -NR"C(0)R\ - NRnC(0)2R\ -NR'- C(0)NR"R"\ -NH-C(NH2)=NH, -NR'C(NH2)=NH, -NH-C(NH2)=NR\ -S(0)R\ -S(0)2NR'R", -NR'S(0)2R" and -N3l where R', R" and R"' each independently hydrogen, halogen, unsubstituted Ci.8 alkyl, unsubstituted or C3.6 cycloalkyl, unsubstituted C^alkenyl, unsubstituted C2.8 alkynyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted heterocyclyl. 27. A modulator having the structure (II): where n=0-4 where each Y is independently hydrogen or halogen; R3, R4, and R5are each independently R3, R4, and R5 are each independently selected from the group consisting of hydrogen, halogen, and -OR'; or any two of R3, R4, and R5, together with the atoms which they substituted, form unsubstituted or substituted 3- to 10- membered heterocyclyl; and R7 is selected from the group consisting of hydrogen, -C(0)R\ -C02R\ -C(0)NR'R", -S02R, unsubstituted or substituted C^ alkyl (optionally C1-8 alkoxyalkyloxy, CH2CH20CH2CH20Me)alkyl> unsubstituted or substituted C2-B alkenyl, unsubstituted or substituted C2.8 alkynyl, unsubstituted or substituted C3-8 cycloalkyi, unsubstituted or substituted C6-io aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl. 28. The modulator of claim 27, where R7 is Ci-a alkoxyalkyloxy. 29. The modulator of claim 27, where n is 1. 30. A modulator comprising one of the following formulae: 31. A pharmaceutical composition comprising the modulator of claim 1 and a pharmaceutical^ acceptable carrier. 32. A pharmaceutical composition comprising the modulator of claim 27 and a pharmaceutical^ acceptable carrier. 33. A pharmaceutical composition comprising the modulator of claim 2830 and a pharmaceutical^ acceptable carrier. 34. A pharmaceutical composition comprising a compound of the formulae: and a pharmaceutical^ acceptable carrier. 35. A method of inhibiting the binding of chemokines l-TAC and/or SDF-1 to a CCXCKR2 receptor, comprising contacting the composition of claim 3234 with a cell that expresses the CCXCKR2 receptor for a time sufficient to inhibit the binding of the chemokines to the CCXCKR2 receptor. 36. A method of inhibiting the binding of chemokines l-TAC and/or SDF-1 to a CCXCKR2 receptor, comprising contacting the modulator of claim 1 with a cell that expresses the CCXCKR2 receptor for a time sufficient to inhibit the binding of the chemokines to the CCXCKR2 receptor. 37, A method of treating cancer, comprising administering a therapeutically effective amount of the composition of claim 3234 to a cancer patient for a time sufficient to treat the cancer. 38. A method of treating cancer, comprising administering a therapeutically effective amount of the modulator of claim 1 to a cancer patient for a time sufficient to treat the cancer. Dated this 17 day of June 2005

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