Claims for Patent: 6,949,535

Summary for Patent: 6,949,535

Title:	Inhibitors of human phosphatidyl-inositol 3-kinase delta
Abstract:	Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3Kδ plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Kδ, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity. Methods of using PI3Kδ inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Kδ inhibitory compounds to inhibit PI3Kδ-mediated processes in vitro and in vivo.
Inventor(s):	Chanchal Sadhu, Ken Dick, Jennifer Treiberg, C. Gregory Sowell, Edward A. Kesicki, Amy Oliver
Assignee:	Icos Corp
Application Number:	US10/697,912
Patent Claims:	1. A method of disrupting leukocyte function comprising a step of contacting leukocytes with a compound having a structure wherein A is an optionally substituted monocyclic 5-membered heterocyclic ring system containing two or three nitrogen atoms or a bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the bicyclic system is aromatic; X is selected from the group consisting of C(Rb)2, CH2CHRb, and CH═C(Rb); Y is selected from the group consisting of null, S, SO, and SO2, NH, O, C(═O), OC(═O), C(═O)O, and NHC(═O)CH2S; R1 and R2, independently, are selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, halo, NHC(═O)C1-3alkyleneN(Ra)2, NO2, ORa, CF3, OCF3, N(Ra)2, CN, OC(═O)Ra, C(═O)Ra, C(═O)ORa, arylORb, Het, NRaC(═O)C1-3alkyleneC(═O)ORa, arylOC1-3alkyleneN(Ra)2, arylOC(═O)Ra, C1-4alkyleneC(═O)ORa, OC1-4alkyleneC(═O)ORa, C1-4alkyleneOC1-4alkyleneC(═O)—ORa, C(═O)NRaSO2Ra, C1-4alkyleneN(Ra)2, C2-6alkenylene-N(Ra)2, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, OC2-4alkyleneN(Ra)2, OC1-4alkyleneCH(ORb)CH2N(Ra)2, OC1-4alkyleneHet, OC2-4alkyleneORa, OC2-4alkyleneNRaC(═O)—ORa, NRaC1-4alkyleneN(Ra)2, NRaC(═O)Ra, NRaC(═O)N(Ra)2, N(SO2C1-4alkyl)2, NRa(SO2C1-4alkyl), SO2N(Ra)2, OSO2CF3, C1-3alkylenearyl, C1-4alkyleneHet, C1-6alkyleneORb, C1-3alkyleneN(Ra)2, C(═O)N(Ra)2, NHC(═O)C1-C3alkylenearyl, C3-8cycloalkyl, C3-8heterocycloalkyl, arylOC1-3alkylene-N(Ra)2, arylOC(═O)Rb, NHC(═O)C1-3alkyleneC3-8heterocyclo-alkyl, NHC(═O)C1-3alkyleneHet, OC1-4alkyleneOC1-4alkylene-C(═O)ORb, C(═O)C1-4alkyleneHet, and NHC(═O)haloC1-6alkyl; or R1 and R2 are taken together to form a 3- or 4-membered alkylene or alkenylene chain component of a 5- or 6-membered ring, optionally containing at least one heteroatom; R3 is selected from the group consisting of optionally substituted hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-4alkylenecycloalkyl, C2-6alkenyl, C1-3alkylenearyl, arylC1-3alkyl, C(═O)Ra, aryl, heteroaryl, C(═O)ORa, C(═O)N(Ra)2, C(═S)N(Ra)2, SO2Ra, SO2N(Ra)2, S(═O)Ra, S(═O)N(Ra)2, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, C(═O)C1-4alkylenearyl, C(═O)C1-4alkyleneheteroaryl, C1-4alkylenearyl substituted with one or more of SO2N(Ra)2, N(Ra)2, C(═O)ORa, NRaSO2CF3, CN, NO2, C(═O)Ra, ORa, C1-4alkyleneN(Ra)2, and OC1-4alkyleneN(Ra)2, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(═O) C1-4alkylenearyl, C1-4alkyleneC(═O)—C1-4alkyleneheteroaryl, C1-4alkyleneC(═O)Het, C1-4alkyleneC(═O)N(Ra)2, C1-4alkyleneORa, C1-4alkyleneNRaC(═O)Ra, C1-4alkyleneOC1-4alkyleneORa, C1-4alkyleneN(Ra)2, C1-4alkyleneC(═O)ORa, and C1-4alkyleneOC1-4alkyleneC(═O)ORa; Rais selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-3alkyleneN(Rc)2, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl; or two Ragroups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom; Rb is selected from the group consisting of hydrogen, C1-6alkyl, heteroC1-3alkyl, C1-3alkyleneheteroC1-3alkyl, arylheteroC1-3alkyl, and aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, and C1-3alkyleneheteroaryl; Rc is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, aryl, and heteroaryl; Het is a 5- or 6-membered heterocyclic ring, saturated or partially or fully unsaturated, containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, selected from the group consisting of 1,3-dioxolane, 2-pyrazoline, pyrazolidine, pyrrolidine, piperazine, pyrroline, 2H-pyran, 4H-pyran, morpholine, thiomorpholine, piperidine, 1,4-dithiane, and 1,4-dioxane, and optionally substituted with C1-4alkyl or C(═O)ORa; and pharmaceutically acceptable salts or solvates, in an amount sufficient to inhibit phosphatidylinositol 3-kinase delta activity in said leukocytes. 2. The method according to claim 1 wherein the compound is selected from the group consisting of 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-6,7-dimethoxy-3H-quinazolin-4-one 2-(6-aminopurin-o-ylmethyl)-6-bromo-3-(2-chlorophenyl)-3H-quinazolin-4-one 2-(6-aminopurin-o-ylmethyl)-3-(2-chlorophenyl)-7-fluoro-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-6-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-5-fluoro-3H-quinazolin-4-one 2-(6-aminopurin-o-ylmethyl)-5-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-5-methyl-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-8-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-biphenyl-2-yl-5-chloro-3H-quinazolin-4-one 5-chloro-2-(9H-purin-6-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-chloro-3-(2-fluorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-fluorophenyl)-3H-quinazolin-4-one 3-biphenyl-2-yl-5-chloro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 5-chloro-3-(2-methoxyphenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-5-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-6,7-dimethoxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 6-bromo-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-8-trifluoromethyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-benzo[g]quinazolin-4-one 6-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 8-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-7-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-7-nitro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-6-hydroxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 5-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-6,7-difluoro-2-(9H-purin-6-ylsullfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-6-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-(2-isopropylphenyl)-5-methyl-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 3-(2-fluorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-o-tolyl-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-methoxyphenyl)-3H-quinazolin-4-one 2-(2-amino-9H-purin-6-ylsulfanylmethyl)-3-cyclopropyl-5-methyl-3H-quinazolin-4-one 3-cyclopropylmethyl-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-cyclopropylmethyl-5-methyl-3H-quinazolin-4-one 2-(2-amino-9H-purin-6-ylsulfanylrnethyl)-3-cyclopropylmethyl-5-methyl-3H-quinazolin-4-one 5-methyl-3-phenethyI-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(2-amino-9H-purin-6-ylsulfanylmethyl)-5-methyl-3-phenethyl-3H-quinazolin-4-one 3-cyclopentyl-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-cyclopentyl-5-methyl-3H-quinazolin-4-one 3-(2-chloropyridin-3-yl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-(2-chloropyridin-3-yl)-5-methyl-3H-quinazolin-4-one 3-methyl-4-[5-methyl-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]-benzoic acid 3-cyclopropyl-5-methyl-2-(9H-purin-6-ylsulfanylinethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-cyclopropyl-5-methyl-3H-quinazolin-4-one 5-methyl-3-(4-nitrobenzyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-cyclohexyl-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-cyclohexyl-5-methyl-3H-quinazolin-4-one 2-(2-amino-9H-purin-6-ylsulfanylmethyl)-3-cyclchexyl-5-methyl-3H-quinazolin-4-one 5-methyl-3-(E-2-phenylcyclopropyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-5-fluoro-2-[(9H-purin-6-ylamino)-methyl]-3H-quinazolin-4-one 2-[(2-amino-9H-purin-6-ylamino)methyl]-3-(2-chlorophenyl)-5-fluoro-3H-quinazolin-4-one 5-methyl-2-[(9H-purin-6-ylamino)methyl]-3-o-tolyl-3H-quinazolin-4-one 2-[(2-amino-9H-purin-6-ylaminomethyl]-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-[(2-fluoro-9H-purin-6-ylamino)methyl]-5-methyl-3-o-tolyl-3H-quinazolin-4-one (2-chlorophenyl)-dimethylamino-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 5-(2-benzyloxyethoxy)-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 6-aminopurine-9-carboxylic acid 3-(2-chlorophenyl)-5-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl ester N-[3-(2-chlorophenyl)-5-fluoro-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2-(9H-purin-6-ylsulfanyl)-acetamide 2-[1-(2-fluoro-9H-purin-6-ylamino)ethyl]-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-[1-(9H-purin-6-ylamino)ethyl]-3-o-tolyl-3H-quinazolin-4-one 2-(6-dimethylaminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(2-methyl-6-oxo-1,6-dihydro-purin-7-ylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(2-methyl-6-oxo-1,6-dihydro-purin-9-ylmethyl)-3-o-tolyl-3H-quinazolin-4-One 2-(amino-dimethylaminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(2-amino-9H-purin-6-ylsulfanylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(4-amino-1,3,5-triazin-2-ylsulfanylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(7-methyl-7H-purin-6-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(2-oxo-1,2-dihydro-pyrimidin-4-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-purin-7-ylmethyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-purin-9-ylmethyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(9-methyl-9H-purin-6-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 2-(2,6-Diamino-pyrimidin-4-ylsulfanylniethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidifl-7-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(2-methylsulfanyl-9H-purin-6-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 2-(2-hydroxy-9H-purin-6-ylsulfanylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 5-methyl-3-o-tolyl-2-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(2-amino- 6-chloro-purin-9-yimethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(6-aminopurin-7-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(7-amino-1,2,3-triazolo[4,5-d]pyrimidin-3-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(7-amino-1,2,3-triazolo[4,5-d]pyrimidin-1-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(6-amino-9H-purin-2-ylsulfanylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(2-amino-6-ethylamino-pyrimidin-4-ylsulfanylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(3-amino-5-methylsulfanyl-1,2,4-triazol-1-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(5-amino-3-methylsulfanyl-1,2,4-triazol-1-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(6-methylaminopurin-9-ylmethyl)-3-o-tolyl-3H-quinazolin-4-one 2-(6-benzylaminopurin-9-yimethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(2,6-diaminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3-o-tolyl-3H-quinazolin-4-one 3-isobutyl-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one N-{2-[5-Methyl-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]-phenyl}-acetamide 5-methyl-3-(E-2-methyl-cyclohexyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-[5-methyl-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]-benzoic acid 3-{2-[(2-dimethylaminoethyl)methylamino]phenyl}-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-5-methoxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-(2-chlorophenyl)-5-(2-morpholin-4-yl-ethylamino)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 3-benzyl-5-methoxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-(2-benzyloxyphenyl)-5-methyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-hydroxyphenyl)-5-methyl-3H-quinazolin-4-one; 2-(1-(2-amino-9H-purin-6-ylamino)ethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 5-methyl-2-[1-(9H-purin-6-ylamino)propyl]-3-o-tolyl-3H-quinazolin-4-one; 2-(1-(2-fluoro-9H-purin-6-ylamino)propyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 2-(1-(2-amino-9H-purin-6-ylamino)propyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 2-(2-benzyloxy-1-(9H-purin-6-ylamino)ethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-{2-(2-(1-methylpyrrolidin-2-yl)-ethoxy)-phenyl}-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-(3-dimethylaminopropoxy)-phenyl)-5-methyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-(2-prop-2-ynyloxyphenyl)-3H-quinazolin-4-one; and 2-{2-(1-(6-aminopurin-9-ylmethyl)-5-methyl-4-oxo-4H-quinazolin-3-yl[-phenoxy}-acetamide. 3. A method of inhibiting kinase activity of a phosphatidylinositol 3-kinase delta polypeptide comprising a step of contacting the polypeptide with a compound having a structure wherein A is an optionally substituted monocyclic 5-membered heterocyclic ring system containing two or three nitrogen atoms or a bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the bicyclic system is aromatic; X is selected from the group consisting of C(Rb)2, CH2CHRb, and CH═C(Rb); Y is selected from the group consisting of null, S, SO, and SO2, NH, O, C(═O), OC(═O), C(═O)O, and NHC(═O)CH2S; R1 and R2, independently, are selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, halo, NHC(═O)C1-3alkyleneN(Ra)2, NO2, ORa, CF3, OCF3, N(Ra)2, CN, OC(═O)Ra, C(═O)Ra, C(═O)ORa, arylORb, Het, NRaC(═O)C1-3alkyleneC(═O)ORa, arylOC1-3alkyleneN(Ra)2, arylOC(═O)Ra, C1-4alkyleneC(═O)ORa, OC1-4alkyleneC(═O)ORa, C1-4alkyleneOC1-4alkyleneC(═O)ORa, C(═O)NRaSO2Ra, C1-4alkyleneN(Ra)2, C2-6alkenyleneN(Ra)2, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, OC2-4alkyleneN(Ra)2, OC1-4alkyleneCH(ORb)CH2N(Ra)2, OC1-4alkyleneHet, OC2-4alkyleneORa, OC2-4alkyleneNRaC(═O)ORa, NRaC1-4alkyleneN(Ra)2, NRaC(═O)Ra, NRaC(═O)—N(Ra)2, N(SO2C1-4alkyl)2, NRa(SO2C1-4alkyl), SO2N(Ra)2, OSO2CF3, C1-3alkylenearyl, C1-4alkyleneHet, C1-6alkyleneORb, C1-3alkyleneN(Ra)2, C(═O)N(Ra)2, NHC(═O)C1-C3alkylenearyl, C3-8cycloalkyl, C3-8heterocycloalkyl, arylOC1-3alkyleneN(Ra)2, arylOC(═O)Rb, NHC(═O)C1-3alkyleneC3-8heterocycloalkyl, NHC(═O)C1-3alkyleneHet, OC1-4alkyleneOC1-4alkyleneC(O)ORb, C(═O)C1-4alkyleneHet, and NRC(═O)haloC1-6alkyl; or R1 and R2 are taken together to form a 3-or 4-membered alkylene or alkenylene chain component of a 5- or 6-mernbered ring, optionally containing at least one heteroatom; R3 is selected from the group consisting of optionally substituted hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-4alkylenecycloalkyl, C2-6alkenyl, C1-3alkylenearyl, arylC1-3alkyl, C(═O)Ra, aryl, heteroaryl, C(═O)ORa, C(═O)N(Ra)2, C(═S)N(Ra)2, SO2Ra, SO2N(Ra)2, S(═O)Ra, S(═O)N(Ra)2, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, C(═O)C1-4alkylenearyl, C(═O)C1-4alkyleneheteroaryl, C1-4alkylenearyl substituted with one or more of SO2N(Ra)2, N(Ra)2, C(═O)ORa, NRaSO2CF3, CN, NO2, C(═O)Ra, ORa, C1-4alkyleneN(Ra)2, and OC1-4alkyleneN(Ra)2, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(═O)C1-4alkylenearyl, C1-4alkyleneC(═O)C1-4alkyleneheteroaryl, C1-4alkyleneC(═O)Het, C1-4alkyleneC(═O)N(Ra)2, C1-4alkyleneORa, C1-4alkyleneNRaC(═O)Ra, C1-4alkyleneOC1-4alkyleneORa, C1-4alkyleneN(Ra)2, C1-4alkyleneC(═O)ORa, and C1-4alkyleneOC1-4alkyleneC(═O) ORa; Ra is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-3alkyleneN(Rc)2, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl; or two Ra groups are taken together to form a 5-or 6-membered ring, optionally containing at least one heteroatom; Rb is selected from the group consisting of hydrogen, C1-6alkyl, heteroC1-3alkyl, C1-3alkyleneheteroC1-3alkyl, arylheteroC1-3alkyl, and aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, and C1-3alkyleneheteroaryl; Rc is selected from the group consisting of hydrogen, C1-6alkyl, C3-6cycloalkyl, aryl, and heteroaryl; Het is a 5- or 6-menibered heterocyclic ring, saturated or partially or fully unsaturated, containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur; selected from the group consisting of 1,3-dioxolane, 2-pyrazoline, pyrazolidine, pyrrolidine, piperazine, pyrroline, 2H-pyran, 4H-pyran, morpholine, thiomorpholine, piperidine, 1,4-dithiane, and 2,4-dioxane, and optionally substituted with C1-4alkyl or C(═O)ORa; and pharmaceutically acceptable salts or solvates thereof. 4. A compound having a general structural formula wherein A is an optionally substituted monocyclic 5-membered heterocyclic ring system containing two or three nitrogen atoms or a bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the cyclic system is aromatic; X is selected from the group consisting of C(Rb)2, CH2CHRb, and CH═C(Rb); Y is selected from the group consisting of null, S, SO, and SO2, NH, O, C(═O), OC(═O), C(═O)O, and NHC(═O)CH2S; R1 and R2, independently, are selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, halo, NHC(═O)C1-3alkyleneN(Ra)2, NO2, ORa, CF3, OCF3, N(Ra)2, CN, OC(═O)Ra, C(═O)Ra, C(═O)ORa, arylORb, Het, NRaC(═O)C1-3alkyleneC(═O)ORa, arylOC1-3alkyleneN(Ra)2, arylOC(═O)Ra, C1-4alkyleneC(═O)ORa, OC1-4alkyleneC(═O) ORa, C1-4alkyleneOC1-4alkyleneC(═O)ORa, C(═O)—NRaSO2Ra, C1-4alkyleneN(Ra)2, C2-6alkenyleneN(Ra)2, C(═O)—NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, OC2-4alkyleneN(Ra)2, OC1-4alkyleneCH(ORb)CH2N(Ra)2, OC1-4alkyleneHet, OC2-4alkyleneORa, OC2-4alkyleneNRaC(═O)ORa, NRaC1-4alkyleneN(Ra)2, NRaC(═O)Ra, NRaC(═O)N(Ra)2, N(SO2C1-4alkyl)2, NRa(SO2C1-4alkyl), SO2N (Ra)2, OSO2CF3, C1-3alkylenearyl, C1-4alkyleneHet, C1-6alkyleneORb, C1-3alkyleneN(Ra)2, C(═O)N(Ra)2, NHC(═O)C1-C3alkylenearyl, C3-8cycloalkyl, C3-8heterocycloalkyl, arylOC1-3alkyleneN(Ra)2, arylOC(═O)Rb, NHC(═O)C1-3alkyleneC3-8heterocycloalkyl, NHC(═O) C1-3alkyleneHet, OC1-4alkyleneOC1-4alkyleneC(═O)ORb, C(═O)C1-4alkyleneHet, and NHC(═O)haloC1-6alkyl; or R1 and R2 are taken together to form a 3-or 4-membered alkylene or alkenylene chain component of a 5-or 6-membered ring, optionally containing at least one heteroatom; R3 is selected from the group consisting of optionally substituted hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-4alkylenecycloalkyl, C2-6alkenyl, C1-3alkylenearyl, arylC1-3alkyl, C(═O)Ra, aryl, heteroaryl, C(═O)ORa, C(═O)N(Ra)2, C(═S)N(Ra)2, SO2Ra, SO2N(Ra)2, S(═O)Ra, S(═O)N(Ra)2, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkyleneHet, C(═O)C1-4alkylenearyl, C(═O)C1-4alkyleneheteroaryl, C1-4alkylenearyl substituted with one or more of SO2N(Ra)2, N(Ra)2, C(═O)ORa, NRaSO2CF3, CN, NO2, C(═O)Ra, ORa, C1-4alkyleneN(Ra)2, and OC1-4alkyleneN(Ra)2, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(═O)C1-4alkylenearyl, C1-4alkyleneC(O)—C1-4alkyleneheteroaryl, C1-4alkyleneC(═O) Het, C1-4alkyleneC(═O)N(Ra)2, C1-4alkyleneORa, C1-4alkyleneNRaC(═O)Ra, C1-4alkyleneOC1-4alkyleneORa, C1-4alkyleneN(Ra)2, C1-4alkyleneC(═O)ORa, and C1-4alkyleneOC1-4alkyleneC(═O)ORa; Rd is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-3alkyleneN(Rc)2, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl; or two Ra groups are taken together to form a 5-or 6-membered ring, optionally containing at least one heteroatom; Rb is selected from the group consisting of hydrogen, C1-6alkyl, heteroC1-3alkyl, C1-3alkyleneheteroC1-3alkyl, arylheteroC1-3alkyl, and aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, and C1-3alkyleneheteroaryl; Rc is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, aryl, and heteroaryl; Het is a 5- or 6-membered heterocyclic ring, saturated or partially or fully unsaturated, containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, selected from the group consisting of 1,3-dioxolane, 2-pyrazoline, pyrazolidine, pyrrolidirie, piperazine, pyrroline, 2H-pyran, 4H-pyran, morpholine, thiomorpholine, piperidine, 1,4-dithiane, and 1,4-dioxane, and optionally substituted with C1-4alkyl or C(═O)ORa; and pharmaceutically acceptable salts or solvates thereof, with the provisos that if X—Y is CH2S, then R3 is different from and if X—Y is CH2S, then R3 is different from —CH2CH(OH)CH2OH substituted phenyl. 5. The compound of claim 4 wherein X is selected from the group consisting of CH2, CH2CH2, CH═CH, CH(CH3), CH(CH2CH3), and CH2CH(CH3), and C(CH3)2. 6. The compound of claim 5 wherein Y is selected from the group consisting of null, S, and NH. 7. The compound of claim 5 wherein the A ring system is selected from the group consisting of 8. The compound of claim 7 wherein the A ring system is substituted with one to three substituents selected from the group consisting of N(Ra)2, halo, C1-3alkyl, S(C1-3alkyl), ORa, and 9. The compound of claim 8 wherein the A ring system is substituted with one to three substituents selected from the group consisting of NH2, NH(CH3), N(CH3)2, NHCH2C6H5, NH(C2H5), Cl, F, CH3, SCH3, OH, and 10. The compound of claim 5 wherein R1 and R2, independently, are selected from the group consisting of hydrogen, ORa, halo, C1-6alkyl, CF3, NO2, N(Ra)2, NRaC1-3alkyleneN(Ra)2, and OC1-3alkyleneORa, specific substituents include, but are not limited to, H, OCH3, Cl, Br, F, CH3, CF3, NO2, OH, N(CH3)2, and O(CH2)2OCH2C6H5, or R1 and R2 are taken together to form a five- or six-membered ring. 11. The compound of claim 5 wherein R3 is selected from the group consisting of C1-6alkyl, aryl, heteroaryl, C3-8cycloalkyl, C3-8heterocycloalkyl, C(═O)ORa, C1-4alkyleneHet, C1-4alkylenecycloalkyl, C1-4alkylenearyl, C1-4alkyleneC(═O)C1-4alkylenearyl, C1-4alkyleneC(═O) ORa, C1-4alkyleneC(═O)N(Ra)2, C1-4alkyleneC(═O)Het, C1-4alkyleneN(Ra)2, and C1-4alkyleneNRaC(═O) Ra. 12. The compound of claim 5 wherein R3 is selected from the group consisting of ORa, C1-6alkyl, aryl, heteroaryl, NO2, N(Ra)2, NRaC(═O)Ra, C(═O)OC2H5, CH2CH(CH3)2, 13. The compound of claim 4 wherein R3 is substituted with a substituent selected from the group consisting of halo, ORa, C1-6alkyl, aryl, heteroaryl, NO2, N(Ra)2, NRaSO2CF3, NRaC(═O)Ra, C(═O)ORa, SO2N(Ra)2, CN, C(═O)Ra, C1-4alkyleneN(Ra)2, OC1-4alkyleneC≡CRa, OC1-4alkyleneC(═O)N(Ra)2, OC1-4alkylenearyl, OC1-4alkyleneheteroaryl, OC1-4alkyleneHet, OC1-4alkyleneN(Ra)2, and N(Ra)C1-4alkyleneN(Ra)2. 14. The compound of claim 4 wherein R3 is substituted with a substituent selected from the group consisting of Cl, F, CH3, CH(CH3)2, OH, OCR3, OCH2C6H5, O(CH2)3N(CH3)2, OCH2C≡CH, OCH2C(═O)NH2, C6H5, NO2, NH2, NHC(═O)CH3, CO2H, and N(CH3)CH2CH2N(CH3)2, and 15. The compound of claim 4 selected from the group consisting of: 2-(6-aminopurin-9ylmethyl)-3-(2-benzyloxyphenyl)-5-methyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-hydroxyphenyl)-5-methyl-3H-quinazolin-4-one; 2-(1-(2-amino-9H-purin-6-ylamino)ethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 5-methyl-2-[1-(9H-purin-6-ylamino)propyl]-3-o-tolyl-3H-quinazolin-4-one; 2-(1-(2-fluoro-9H-purin-6ylamino)propyl)-5-methyl-3-o-tolyl-3H-quinazolin-4one; 2-(1-(2-amino-9H-purin-6-ylamino)propyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 2-(2-benzyloxy-1-(9H-purin-6-ylamino)ethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-{2-(2-(1-methylpyrrolidin-2-yl)-ethoxy)-phenyl}-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-(3-dimethylaminopropoxy)-phenyl)-5-methyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-(2-prop-2-ynyloxyphenyl)-3H-quinazolin-4-one; and 2-{2-(1-(6-aminopurin-9-ylmethyl)-5-methyl-4-oxo-4H-quinazolin-3-yl)-phenoxy}-acetamide.