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Claims for Patent: 6,800,620

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Claims for Patent: 6,800,620

Title: Inhibitors of human phosphatidylinositol 3-kinase delta
Abstract:Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K.delta.) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3K.delta. plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K.delta., while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K.delta. activity, including compounds that selectively inhibit PI3K.delta. activity. Methods of using PI3K.delta. inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K.delta. inhibitory compounds to inhibit PI3K.delta.-mediated processes in vitro and in vivo.
Inventor(s): Sadhu; Chanchal (Bothell, WA), Dick; Ken (Bothell, WA), Treiberg; Jennifer (Bothell, WA), Sowell; C. Gregory (Mukilteo, WA), Kesicki; Edward A. (Bothell, WA), Oliver; Amy (Bothell, WA)
Assignee: ICOS (Bothell, WA)
Application Number:10/337,192
Patent Claims: 1. A method of inhibiting the growth or proliferation of chronic myelogenous leukemia cells comprising contacting the cells with a compound that selectively inhibits phosphatidylinositol 3-kinase delta activity in the cancer cells relative to other Type I PI3K isoforms in a cell-based assay.

2. A compound having a structure ##STR80## wherein Y is selected from the group consisting of null, S, and NH; R.sup.4 is selected from the group consisting of H, halogen, NO.sub.2, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; R.sup.5 is selected from the group consisting of H, OCH.sub.3, and halo; or R.sup.4 and R.sup.5 together with C-6 and C-7 of the quinazoline ring system define a 5- or 6-membered aromatic ring optionally containing one or more O, N, or S atoms; R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkoxyphenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, C(.dbd.O)OC.sub.2 H.sub.5, and morpholinyl; R.sup.d, independently, is selected from the group consisting of NH.sub.2, halo, C.sub.1-3 alkyl, S(C.sub.1-3 alkyl), OH, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2, NH(C.sub.1-3 alkylenephenyl), and ##STR81## q is 1 or 2; and pharmaceutically acceptable salts and solvates thereof, provided that at least one of R.sup.4 and R.sup.5 is other than H when R.sup.6 is phenyl or 2-chlorophenyl.

3. The compound of claim 2 selected from the group consisting of: 3-(2-isopropylphenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazoli n-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; 3-(2-fluorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2-methoxyphenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin- 4-one; 3-(2,6-dichlorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 3-(2-chlorophenyl)-6-fluoro-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-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-benzyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-butyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(2-chlorophenyl)-7-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-morpholin-4-yl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one, acetate salt; 8-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2-chlorophenyl)-6,7-difluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 3-(3-methoxyphenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 6-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(3-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 2-(9H-purin-6-ylsulfanylmethyl)-3-pyridin-4-yl-3H-quinazolin-4-one; 3-(2-chlorophenyl)-8-trifluoromethyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-qui nazolin-4-one; 3-benzyl-5-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(4-methylpiperazin-1-yl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4- one, acetate salt; 3-(2-chlorophenyl)-6-hydroxy-2-(9H-purin-6-ylsulfanzylmethyl)-3H-quinazolin -4-one; [5-fluoro-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]acetic acid ethyl ester; 3-(2-methoxyphenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-biphenyl-2-yl-5-chloro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-on e; 5-chloro-3-(2-methoxyphenyl)-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; 2-(6-aminopurin-9-ylmethyl)-3-biphenyl-2-yl-5-chloro-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-fluorophenyl)-5-methyl-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-fluorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-8-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-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)-3-(2-chlorophenyl)-5-fluoro-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-3-benzyl-5-fluoro-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-butyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-morpholin-4-yl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-7-fluoro-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-6-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one ; 3-(4-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(2-chlorophenyl)-6,7-dimethoxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazo line-4-one; 3-(2-chlorophenyl)-7-nitro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4- one; 2-(6-aminopurin-9-ylmethyl)-6-bromo-3-(2-chlorophenyl)-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-6,7-dimethoxy-3H-quinazolin- 4-one; 6-bromo-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4- one; 3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-benzo[g]quinazolin-4- one; 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-o-tolyl-3H-quinazolin-4-one; and 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-methoxyphenyl)-3H-quinazolin-4-on e.

4. The compound of claim 2 wherein R.sup.4 is selected from the group consisting of H, halo, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, C(.dbd.O)OC.sub.2 H.sub.5, and morpholinyl; wherein (a) R.sup.4 and R.sup.5, independently, are different from 6-halo or 6,7-dimethoxy groups; (b) R.sup.6 is different from 4-chlorophenyl; and (c) at least one of R.sup.4 and R.sup.5 is different from H when R.sup.6 is phenyl or 2-chlorophenyl and X is S.

5. The compound of claim 3 is selected from the group consisting of 3-(2-isopropylphenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazoli n-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; 3-(2-fluorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2,6-dichlorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 3-(2-chlorophenyl)-6-fluoro-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)-5-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-benzyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-butyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(2-chlorophenyl)-7-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-morpholin-4-yl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one, acetate salt; 8-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2-chlorophenyl)-6,7-difluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 6-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(3-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 2-(9H-purin-6-ylsulfanylmethyl)-3-pyridin-4-yl-3H-quinazolin-4-one; 3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-trifluoromethyl-3H-quina zolin-4-one; 3-benzyl-5-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(4-methylpiperazin-1-yl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4- one, acetate salt; 3-(2-chlorophenyl)-6-hydroxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin- 4-one; [5-fluoro-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]acetic acid ethyl ester; 3-biphenyl-2-yl-5-chloro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-on e; 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; 2-(6-aminopurin-9-ylmethyl)-3-biphenyl-2-yl-5-chloro-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-fluorophenyl)-5-methyl-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-fluorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-8-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-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)-3-(2-chlorophenyl)-5-fluoro-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-3-benzyl-5-fluoro-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-butyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-morpholin-4-yl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-7-fluoro-3H-quinazolin-4-one ; and 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-o-tolyl-3H-quinazoline-4-one.

6. A compound having a general structural formula ##STR82## wherein A is an optionally substituted monocyclic or bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the system is aromatic; X is selected from the group consisting of CHR.sup.b, CH.sub.2 CHR.sup.b, and CH.dbd.C(R.sup.b); Y is selected from the group consisting of null, S, SO, SO.sub.2, NH, O, C(.dbd.O), OC(.dbd.O), C(.dbd.O)O, and NHC(.dbd.O)CH.sub.2 S; R.sup.1 and R.sup.2, independently, are selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, halo, NHC(.dbd.O)C.sub.1-3 alkyleneN(R.sup.a).sub.2, NO.sub.2, OR.sup.a, OCF.sub.3, N(R.sup.a).sub.2, CN, OC(.dbd.O)R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, arylOR.sup.b, Het, NR.sup.a C(.dbd.O)C.sub.1-3 alkyleneC(.dbd.O)OR.sup.a, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.a, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, OC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C(.dbd.O)NR.sup.a SO.sub.2 R.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.2-6 alkenyleneN(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneN(R.sup.a).sub.2, OC.sub.1-4 alkyleneCH(OR.sup.b)CH.sub.2 N(R.sup.a).sub.2, OC.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneOR.sup.a, OC.sub.2-4 alkyleneNR.sup.a C(.dbd.O)OR.sup.a, NR.sup.a C.sub.1-4 alkyleneN(R.sup.a).sub.2, NR.sup.a C(.dbd.O)R.sup.a, NR.sup.a C(.dbd.O)N(R.sup.a).sub.2, N(SO.sub.2 C.sub.1-4 alkyl).sub.2, NR.sup.a (SO.sub.2 C.sub.1-4 alkyl), SO.sub.2 N(R.sup.a).sub.2, OSO.sub.2 CF.sub.3, C.sub.1-3 alkylenearyl, C.sub.1-4 alkyleneHet, C.sub.1-6 alkyleneOR.sup.b, C.sub.1-3 alkyleneN(R.sup.a).sub.2, C(.dbd.O)N(R.sup.a).sub.2, NHC(.dbd.O)C.sub.1 -C.sub.3 alkylenearyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.b, NHC(.dbd.O)C.sub.1-3 alkyleneC.sub.3-8 heterocycloalkyl, NHC(.dbd.O)C.sub.1-3 alkyleneHet, OC.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.b, C(.dbd.O)C.sub.1-4 alkyleneHet, and NHC(.dbd.O)haloC.sub.1-6 alkyl; or R.sup.1 and R.sup.2 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; R.sup.3 is selected from the group consisting of optionally substituted hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-4 alkylenecycloalkyl, C.sub.2-6 alkenyl, C.sub.1-3 alkylenearyl, arylC.sub.1-3 alkyl, C(.dbd.O)R.sup.a, aryl, heteroaryl, C(.dbd.O)OR.sup.a, C(.dbd.O)N(R.sup.a).sub.2, C(.dbd.S)N(R.sup.a).sub.2, SO.sub.2 R.sup.a, SO.sub.2 N(R.sup.a).sub.2, S(.dbd.O)R.sup.a, S(.dbd.O)N(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, C(.dbd.O)C.sub.1-4 alkylenearyl, C(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkylenearyl optionally substituted with one or more of halo, SO.sub.2 N(R.sup.a).sub.2, N(R.sup.a).sub.2, C(.dbd.O)OR.sup.a, NR.sup.a SO.sub.2 CF.sub.3, CN, NO.sub.2, C(.dbd.O)R.sup.a, OR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, and OC.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneHet, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkylenearyl, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneC(.dbd.O)Het, C.sub.1-4 alkyleneC(.dbd.O)N(R.sup.a).sub.2, C.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneNR.sup.a C(.dbd.O)R.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, and C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a ; R.sup.a is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-3 alkyleneN(R.sup.a).sub.2, aryl, arylC.sub.1-3 alkyl, C.sub.1-3 alkylenearyl, heteroaryl, heteroarylC.sub.1-3 alkyl, and C.sub.1-3 alkyleneheteroaryl; or two R.sup.a groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom; R.sup.b is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, arylC.sub.1-3 alkyl, heteroarylC.sub.1-3 alkyl, C.sub.1-3 alkylenearyl, and C.sub.1-3 alkyleneheteroaryl; 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, and optionally substituted with C.sub.1-4 alkyl or C(.dbd.O)OR.sup.a ; and pharmaceutically acceptable salts and solvates thereof, with the provisos that if X--Y is CH.sub.2 S, then R.sup.3 is different from ##STR83## and if X--Y is CH.sub.2 S, then R.sup.3 is different from --CH.sub.2 CH(OH)CH.sub.2 OH substituted phenyl.

7. The compound of claim 6 wherein X is selected from the group consisting of CH.sub.2, CH.sub.2 CH.sub.2, CH.dbd.CH, CH(CH.sub.3), CH.sub.2 CH(CH.sub.3), and C(CH.sub.3).sub.2.

8. The compound of claim 6 wherein Y is selected from the group consisting of null, S, and NH.

9. The compound of claim 6 wherein the A ring system is selected from the group consisting of imidazolyl, pyrazolyl, 1,2,3-triazolyl, pyridizinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, purinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, 1H-indazolyl, and benzimidazolyl.

10. The compound of claim 6 wherein the A ring system is selected from the group consisting of ##STR84##

11. The compound of claim 6 wherein the A ring system is unsubstituted with one to three substituents selected from the group consisting of N(R.sup.a).sub.2, halo, C.sub.1-3 alkyl, S(C.sub.1-3 alkyl), OR.sup.a, halo, and ##STR85##

12. The compound of claim 6 wherein the A ring system is substituted with one to three substituents selected from the group consisting of NH.sub.2, NH(CH.sub.3), N(CH.sub.3).sub.2, NHCH.sub.2 C.sub.6 H.sub.5, NH(C.sub.2 H.sub.5), Cl, F, CH.sub.3, SCH.sub.3, OH, and ##STR86##

13. The compound of claim 6 wherein R.sup.1 and R.sup.2, independently, selected from the group consisting of hydrogen, OR.sup.a, halo, C.sub.1-6 alkyl, CF.sub.3, NO.sub.2, N(R.sup.a).sub.2, NR.sup.a C.sub.1-3 alkyleneN(R.sup.a).sub.2, and OC.sub.1-3 alkyleneOR.sup.a. Specific substituents include, but are not limited to, H, OCH.sub.3, Cl, Br, F, CH.sub.3, CF.sub.3, NO.sub.2, OH, N(CH.sub.3).sub.2, ##STR87##

and O(CH.sub.2).sub.2 OCH.sub.2 C.sub.6 H.sub.5.

14. The compound of claim 6 wherein R.sup.1 and R.sup.2 are taken together to form a five- or six-membered ring.

15. The compound of claim 6 wherein R.sup.3 is selected from the group consisting of C.sub.1-6 alkyl, aryl, heteroaryl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C(.dbd.O)OR.sup.a, C.sub.1-4 alkyleneHet, C.sub.1-4 alkylenecycloalkyl, C.sub.1-4 alkylenearyl, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkylenearyl, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C.sub.1-4 alkyleneC(.dbd.O)N(R.sup.a).sub.2, C.sub.1-4 alkyleneC(.dbd.O)Het, C.sub.1-4 alkyleneN(R.sup.a).sub.2, and C.sub.1-4 alkyleneNR.sup.a C-(.dbd.O)R.sup.a.

16. The compound of claim 6 wherein R.sup.3 is selected from the group consisting of OR.sup.a, C.sub.1-6 alkyl, aryl, heteroaryl, NO.sub.2, N(R.sup.a).sub.2, NR.sup.a C(.dbd.O)R.sup.a, C(.dbd.O)OC.sub.2 H.sub.5, CH.sub.2 CH(CH.sub.3).sub.2, ##STR88##

17. The compound of claim 6 wherein R.sup.3 is substituted with a substituent selected from the group consisting of halo, OR.sup.a, C.sub.1-6 alkyl, aryl, heteroaryl, NO.sub.2, N(R.sup.a).sub.2, NR.sup.a SO.sub.2 CF.sub.3, NR.sup.a C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, SO.sub.2 N(R.sup.a).sub.2, CN, C(.dbd.O)R.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, OC.sub.1-4 alkyleneN(R.sup.a).sub.2, and N(R.sup.a)C.sub.1-4 alkyleneN(R.sup.a).sub.2.

18. The compound of claim 6 wherein R.sup.3 is substituted with a substituent selected from the group consisting of Cl, F, CH.sub.3, CH(CH.sub.3).sub.2, OCH.sub.3, C.sub.6 H.sub.5, NO.sub.2, NH.sub.2, NHC(.dbd.O)CH.sub.3, CO.sub.2 H, and N(CH.sub.3)CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2.

19. A method of disrupting leukocyte function comprising contacting leukocytes with a compound that selectively inhibits phosphatidylinositol 3-kinase delta (PI3K.delta.) activity in said leukocytes relative to other Type I phosphatidylinositol 3-kinase (PI3K) isoforms in a cell-based assay.

20. The method of claim 19 wherein said leukocytes comprise cells selected from the group consisting of neutrophils, B lymphocytes, T lymphocytes, and basophils.

21. The method of claim 19 wherein said leukocytes comprise neutrophils, and wherein said method comprises disrupting at least one neutrophil function selected from the group consisting of stimulated superoxide release, stimulated exocytosis, and chemotactic migration.

22. The method of claim 21 wherein bacterial phagocytosis or bacterial killing by said neutrophils is substantially undisrupted.

23. The method of claim 19 wherein said leukocytes comprise B lymphocytes, and wherein said method comprises disrupting proliferation of said B lymphocytes or antibody production by said B lymphocytes.

24. The method of claim 23 wherein said method comprises disrupting proliferation of said T lymphocytes.

25. The method of claim 19 wherein said leukocytes comprise basophils, and wherein said method comprises disrupting histamine release by the basophils.

26. The method of claim 19 wherein said compound exhibits at least about a 10-fold selectivity for inhibition of PI3K.delta. relative to other Type I PI3K isoforms in a cell-based assay.

27. The method of claim 26 wherein said compound exhibits at least about a 20-fold selectivity for inhibition of PI3K.delta. relative to other Type I PI3K isoforms in a cell-based assay.

28. The method of claim 27 wherein said compound exhibits at least about a 50-fold selectivity for inhibition of PI3K.delta. relative to other Type I PI3K isoforms in a biochemical assay.

29. The method of claim 19 wherein said compound has the structure: ##STR89## wherein Y is selected from the group consisting of null, S, and NH; R.sup.7 is selected from the group consisting of H, halo, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; R.sup.8 is selected from the group consisting of is H, OCH.sub.3, and halogen; or R.sup.7 and R.sup.8 together with C-6 and C-7 of the quinazoline ring system define a 5- or 6-membered aromatic ring optionally containing one or more O, N, or S atoms; R.sup.9 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, C(.dbd.O)--OC.sub.2 H.sub.5, and morpholinyl; R.sup.d, independently, is selected from the group consisting of NH.sub.2, halo, C.sub.1-3 alkyl, S(C.sub.1-3 alkyl), OH, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2, NH(C.sub.1-3 alkylenephenyl); q is 1 or 2, and pharmaceutically acceptable salts and solvates thereof, provided that at least one of R.sup.7 and R.sup.8 is different from 6-halo or 6,7-dimethoxy groups, and that R.sup.9 is different from 4-chlorophenyl.

30. The method of claim 29 wherein the compound is selected from the group consisting of 3-(2-isopropylphenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazoli n-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; 3-(2-fluorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2-methoxyphenyl)-5-methyl-2-(9H-purin-y-ylsulfanylmethyl-3H-quinazolin-4 -one; 3-(2,6-dichlorophenyl)-5-methyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 3-(2-chlorophenyl)-6-fluoro-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-(3-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-benzyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-butyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(2-chlorophenyl)-7-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-morpholin-4-yl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one, acetate salt; 8-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(2-chlorophenyl)-6,7-difluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazol in-4-one; 3-(2-methoxyphenyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 6-chloro-3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4 -one; 3-(3-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 2-(9H-purin-6-ylsulfanylmethyl)-3-pyridin-4-yl-3H-quinazolin-4-one; 3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-trifluoromethyl-3H-quina zolin-4-one; 3-benzyl-5-fluoro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-(4-methylpiperazin-1-yl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4- one, acetate salt; 3-(2-chlorophenyl)-6-hydroxy-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin- 4-one; [5-fluoro-4-oxo-2-(9H-purin-6-ylsulfanylmethyl)-4H-quinazolin-3-yl]acetic acid ethyl ester; 3-(2,4-dimethoxyphenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one ; 3-biphenyl-2-yl-5-chloro-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-on e; 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; 2-(6-aminopurin-9-ylmethyl)-3-biphenyl-2-yl-5-chloro-3H-quinazolin-4-one; 5-chloro-3-(2-methoxyphenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin- 4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-fluorophenyl)-5-methyl-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-fluorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-8-chloro-3-(2-chlorophenyl)-3H-quinazolin-4-one ; 2-(6-aminopurin-9-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)-3-(2-chlorophenyl)-5-fluoro-3H-quinazolin-4-one ; 2-(6-aminopurin-9-ylmethyl)-3-benzyl-5-fluoro-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-butyl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-morpholin-4-yl-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-3-(2-chlorophenyl)-7-fluoro-3H-quinazolin-4-one ; 3-(2-chlorophenyl)-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 3-phenyl-2-(9H-purin-6-ylsulfanylmethyl)-3H-quinazolin-4-one; 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-isopropylphenyl)-3H-quinazolin-4- one; and 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-o-tolyl-3H-quinazolin-4-one.

31. A method for disrupting leukocyte function comprising contacting leukocytes with a compound having a structure ##STR90## wherein A is an optionally substituted monocyclic or bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the system is aromatic; X is selected from the group consisting of CHR.sup.b, CH.sub.2 CHR.sup.b, and CH.dbd.C(R.sup.b); Y is selected from the group consisting of null, S, SO, SO.sub.2, NH, O, C(.dbd.O), OC(.dbd.O), C(.dbd.O)O, and NHC(.dbd.O)CH.sub.2 S; R.sup.1 and R.sup.2, independently, are selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, halo, NHC(.dbd.O) C.sub.1-3 alkyleneN(R.sup.a).sub.2, NO.sub.2, OR.sup.a, OCF.sub.3, N(R.sup.a).sub.2, CN, OC(.dbd.O)R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, arylOR.sup.b, Het, NR.sup.a C(.dbd.O)C.sub.1-3 alkyleneC(.dbd.O)OR.sup.a, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.a, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, OC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C(.dbd.O)-NR.sup.a SO.sub.2 R.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.2-6 alkenyleneN(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneN(R.sup.a).sub.2, OC.sub.1-4 alkyleneCH (OR.sup.b)CH.sub.2 N(R.sup.a).sub.2, OC.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneOR.sup.a, OC.sub.2-4 alkyleneNR.sup.a C(.dbd.O)OR.sup.a, NR.sup.a C.sub.1-4 alkyleneN(R.sup.a).sub.2, NR.sup.a C(.dbd.O)R.sup.a, NR.sup.a C(.dbd.O)N(R.sup.a).sub.2, N(SO.sub.2 C.sub.1-4 alkyl).sub.2, NR.sup.a (SO.sub.2 C.sub.1-4 alkyl), SO.sub.2 N(R.sup.a).sub.2, OSO.sub.2 CF.sub.3, C.sub.1-3 alkylenearyl, C.sub.1-4 alkyleneHet, C.sub.1-6 -alkyleneOR.sup.b, C.sub.1-3 alkyleneN(R.sup.a).sub.2, C(.dbd.O)N(R.sup.a).sub.2, NHC(.dbd.O)C.sub.1 -C.sub.3 alkylenearyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.b, NHC(.dbd.O)C.sub.1-3 alkyleneC.sub.3-8 heterocycloalkyl, NHC(.dbd.O)C.sub.1-3 -alkyleneHet, OC.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.b, C(.dbd.O)C.sub.1-4 alkyleneHet, and NHC(.dbd.O)haloC.sub.1-6 alkyl; or R.sup.1 and R.sup.2 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; R.sup.3 is selected from the group consisting of optionally substituted hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-4 alkylenecycloalkyl, C.sub.2-6 alkenyl, C.sub.1-3 alkylenearyl, arylC.sub.1-3 alkyl, C(.dbd.O)R.sup.a, aryl, heteroaryl, C(.dbd.O)OR.sup.a, C(.dbd.O)N(R.sup.a).sub.2, C(.dbd.S)N(R.sup.a).sub.2, SO.sub.2 R.sup.a, SO.sub.2 N(R.sup.a).sub.2, S(.dbd.O)R.sup.a, S(.dbd.O)N(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, C(.dbd.O)C.sub.1-4 alkylenearyl, C(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkylenearyl substituted with one or more of SO.sub.2 N(R.sup.a).sub.2, N(R.sup.a).sub.2, C(.dbd.O)OR.sup.a, NR.sup.a SO.sub.2 CF.sub.3, CN, NO.sub.2, C(.dbd.O)R.sup.a, OR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, and OC.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneHet, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkylenearyl, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneC(.dbd.O)Het, C.sub.1-4 alkyleneC(.dbd.O)N(R.sup.a).sub.2, C.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneNR.sup.a C(.dbd.O)R.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, and C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a ; R.sup.a is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-3 alkyleneN(R.sup.a).sub.2, aryl, arylC.sub.1-3 alkyl, C.sub.1-3 alkylenearyl, heteroaryl, heteroarylC.sub.1-3 alkyl, and C.sub.1-3 alkyleneheteroaryl; or two R.sup.a groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom; R.sup.b is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, arylC.sub.1-3 alkyl, heteroarylC.sub.1-3 alkyl, C.sub.1-3 alkylenearyl, and C.sub.1-3 alkyleneheteroaryl; 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, and optionally substituted with C.sub.1-4 alkyl or C(.dbd.O)OR.sup.a ; and pharmaceutically acceptable salts and solvates, in an amount sufficient to inhibit phosphatidylinositol 3-kinase delta activity in said leukocytes.

32. The method according to claim 31 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 2-(6-aminopurin-9-ylmethyl)-5-chloro-3-(2-fluorophenyl)-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 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-on e 2-(6-aminopurin-9-ylmethyl)-3-cyclopropylmethyl-5-methyl-3H-quinazolin-4-on e 2-(6-aminopurin-9-ylmethyl)-3-cyclopentyl-5-methyl-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl)-3-chloropyridin-3-yl)-5-methyl-3H-quinazolin-4- one 2-(6-aminopurin-9-ylmethyl)-3-cyclopropyl-5-methyl-3H-quinazolin-4-one 2-(6-aminopurin-9-ylmethyl-3-cyclohexyl-5-methyl-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-quina zolin-4-one 5-methyl-2-[(9H-purin-6-ylamino)methyl]-3-o-tolyl-3H-quinazolin-4one 2-[(2-amino-9H-purin-6-ylamino)methyl]-5-methyl-3-o-tolyl-3H-quinazolin-4-o ne 2-[(2-fluoro-9H-purin-6-ylamino)methyl]-5-methyl-3-o-tolyl-3H-quinazolin-4- one 6-aminopurine-9-carboxylic acid 3-(2-chlorophenyl)-5-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl ester 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-quina zolin-4-one 5-methyl-2-(2-methyl-6-oxo-1,6-dihydro-purin-9-ylmethyl)-3-o-tolyl-3H-quina zolin-4-one 2-(amino-dimethylaminopurin-9-ylmethyl)-5-methyl-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 2-(2-amino-6-chloro-purin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-on e 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 5-methyl-2-(6-methylaminopurin-9-ylmethyl)-3-o-tolyl-3H-quinazolin-4-one 2-(6-benzylaminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one 2-(2,6-diaminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one.

33. A method of ameliorating a medical condition mediated by PI3K.delta. activity in leukocytes comprising administering to an animal in need thereof a therapeutically effective amount of a compound that selectively inhibits phosphatidylinositol 3-kinase delta activity in said leukocytes relative to other Type I PI3K isoforms in a cell-based assay.

34. The method of claim 33 wherein said medical condition is characterized by an undesirable neutrophil function selected from the group consisting of stimulated superoxide release, stimulated exocytosis, and chemotactic migration.

35. The method of claim 34 wherein phagocytic activity or bacterial killing by said neutrophils is substantially unaffected.

36. A method of disrupting a function of osteoclasts comprising contracting osteoclasts with a compound that selectively inhibits phosphatidylinositol 3-kinase delta activity in said osteoclasts relative to other Type I PI3K isoforms in a cell-based assay.

37. The method of claim 36 wherein said compound has a structure ##STR91## wherein Y is selected from the group consisting of null, S, and NH; R.sup.7 is selected from the group consisting of H, halo, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; R.sup.8 is selected from the group consisting of is H, OCH.sub.3, and halogen; or R.sup.7 and R.sup.8 together with C-6 and C-7 of the quinazoline ring system define a 5- or 6-membered aromatic ring optionally containing one or more O, N, or S atoms; R.sup.9 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, C(.dbd.O)-OC.sub.2 H.sub.5, and morpholinyl; R.sup.d, independently, is selected from the group consisting of NH.sub.2, halo, C.sub.1-3 alkyl, S(C.sub.1-3 alkyl)OH, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2, NH(C.sub.1-3 alkylenephenyl); q is 1 or 2, and pharmaceutically acceptable salts and solvates thereof, provided that at least one of R.sup.7 and R.sup.8 is different from 6-halo or 6,7-dimethoxy groups, and further provided that R.sup.9 is different from 4-chlorophenyl.

38. The method of claim 36 wherein said compound comprises a moiety that binds to bone.

39. A method of ameliorating a bone-resorption disorder in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a compound that inhibits phosphatidylinositol 3-kinase delta (PI3K.delta.) activity in osteoclasts of the animal relative to other Type I PI3K isoforms in a cell-based assay.

40. The method of claim 39 wherein said bone-resorption disorder is osteoporosis.

41. The method of claim 1 wherein said compound has a structure ##STR92## wherein R.sup.7 is selected from the group consisting of H, halogen, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; R.sup.8 is selected from the group consisting of H, OCH.sub.3, and halogen; or R.sup.7 and R.sup.8 together with C-6 and C-7 of the quinazoline ring system define a 5- or 6-membered aromatic ring optionally containing one or more O, N, or S atoms; R.sup.9 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, acetic acid ethyl ester, and morpholinyl; X is NH or S; and pharmaceutically acceptable salts and solvates thereof, provided that at least one of R.sup.7 and R.sup.8 is different from 6-halo or 6,7-dimethoxy groups, and further provided that R.sup.9 is different from 4-chlorophenyl.

42. A method of inhibiting kinase activity of a phosphatidylinositol 3-kinase delta polypeptide comprising contacting the polypeptide with a compound having a structure ##STR93## wherein A is an optionally substituted monocyclic or bicyclic ring system containing at least two nitrogen atoms, and at least one ring of the system is aromatic; X is selected from the group consisting of CHR.sup.b, CH.sub.2 CHR.sup.b, and CH.dbd.C(R.sup.b); Y is selected from the group consisting of null, S, SO, SO.sub.2, NH, O, C(.dbd.O), OC(.dbd.O), C(.dbd.O)O, and NHC(.dbd.O)CH.sub.2 S; R.sup.1 and R.sup.2, independently, are selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, halo, NHC(.dbd.O)C.sub.1-3 alkyleneN(R.sup.a).sub.2, NO.sub.2, OR.sup.a, OCF.sub.3, N(R.sup.a).sub.2, CN, OC(.dbd.O)R.sup.a, C(.dbd.O)R.sup.a, C(.dbd.O)OR.sup.a, arylOR.sup.b, Het, NR.sup.a C(.dbd.O)C.sub.1-3 alkyleneC(.dbd.O)OR.sup.a, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.a, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, OC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, C(.dbd.O)-NR.sup.a SO.sub.2 R.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.2-6 alkenyleneN(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneN(R.sup.a).sub.2, OC.sub.1-4 alkyleneCH(OR.sup.b)CH.sub.2 N(R.sup.a).sub.2, OC.sub.1-4 alkyleneHet, OC.sub.2-4 alkyleneOR.sup.a, OC.sub.2-4 alkyleneNR.sup.a C(.dbd.O)OR.sup.a, NR.sup.a C.sub.1-4 alkyleneN(R.sup.a).sub.2, NR.sup.a C(.dbd.O)R.sup.a, NR.sup.a C(.dbd.O)N(R.sup.a).sub.2, N(SO.sub.2 C.sub.1-4 alkyl).sub.2, NR.sup.a (SO.sub.2 C.sub.1-4 alkyl), SO.sub.2 N(R.sup.a).sub.2, OSO.sub.2 CF.sub.3, C.sub.1-3 alkylenearyl, C.sub.1-4 alkyleneHet, C.sub.1-6 alkyleneOR.sup.b, C.sub.1-3 alkyleneN(R.sup.a).sub.2, C(.dbd.O)N(R.sup.a).sub.2, NHC(.dbd.O)C.sub.1 -C.sub.3 alkylenearyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, arylOC.sub.1-3 alkyleneN(R.sup.a).sub.2, arylOC(.dbd.O)R.sup.b, NHC(.dbd.O)C.sub.1-3 alkyleneC.sub.3-8 heterocycloalkyl, NHC(.dbd.O)C.sub.1-3 alkyleneHet, OC.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.b, C(.dbd.O)C.sub.1-4 alkyleneHet, and NHC(.dbd.O)haloC.sub.1-6 alkyl; or R.sup.1 and R.sup.2 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; R.sup.3 is selected from the group consisting of optionally substituted hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-4 alkylenecycloalkyl, C.sub.2-6 alkenyl, C.sub.1-3 alkylenearyl, arylC.sub.1-3 alkyl, C(.dbd.O)R.sup.a, aryl, heteroaryl, C(.dbd.O)OR.sup.a, C(.dbd.O)N(R.sup.a).sub.2, C(.dbd.S)N(R.sup.a).sub.2, SO.sub.2 R.sup.a, SO.sub.2 N(R.sup.a).sub.2, S(.dbd.O)R.sup.a, S(.dbd.O)N(R.sup.a).sub.2, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneOR.sup.a, C(.dbd.O)NR.sup.a C.sub.1-4 alkyleneHet, C(.dbd.O)C.sub.1-4 alkylenearyl, C(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkylenearyl optionally substituted with one or more of halo, SO.sub.2 N(R.sup.a).sub.2, N(R.sup.a).sub.2, C(.dbd.O)OR.sup.a, NR.sup.a SO.sub.2 CF.sub.3, CN, NO.sub.2, C(.dbd.O)R.sup.a, OR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, and OC.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneHet, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkylenearyl, C.sub.1-4 alkyleneC(.dbd.O)C.sub.1-4 alkyleneheteroaryl, C.sub.1-4 alkyleneC(.dbd.O)Het, C.sub.1-4 alkyleneC(.dbd.O)N(R.sup.a).sub.2, C.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneNR.sup.a C(.dbd.O)R.sup.a, C.sub.1-4 alkyleneOC.sub.1-4 alkyleneOR.sup.a, C.sub.1-4 alkyleneN(R.sup.a).sub.2, C.sub.1-4 alkyleneC(.dbd.O)OR.sup.a, and C.sub.1-4 alkyleneOC.sub.1-4 alkyleneC(.dbd.O)OR.sup.a ; R.sup.a is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, C.sub.1-3 alkyleneN(R.sup.a).sub.2, aryl, arylC.sub.1-3 alkyl, C.sub.1-3 -alkylenearyl, heteroaryl, heteroarylC.sub.1-3 alkyl, and C.sub.1-3 alkyleneheteroaryl; or two R.sup.a groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom; R.sup.b is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl, heteroaryl, arylC.sub.1-3 alkyl, heteroarylC.sub.1-3 alkyl, C.sub.1-3 alkylenearyl, and C.sub.1-3 alkyleneheteroaryl; 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, and optionally substituted with C.sub.1-4 alkyl or C(.dbd.O)OR.sup.a ; and pharmaceutically acceptable salts and solvates thereof.

43. The method of claim 42 wherein R.sup.1 is selected from the group consisting of H, halo, OH, OCH.sub.3, CH.sub.3, and CF.sub.3 ; and R.sup.3 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl, halophenyl, alkylphenyl, biphenyl, benzyl, pyridinyl, 4-methylpiperazinyl, C(.dbd.O)C.sub.2 H.sub.5, and morpholinyl; wherein at least one of R.sup.1 and R.sup.2 is different from 6-halo or 6,7-dimethoxy, and R.sup.3 is different from 4-chlorophenyl.
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