Patent ID: 6518277
Filing Date: 2003-02-11
Classification: A61P,C07D

Abstract:
A method for disrupting leukocyte function comprising contacting leukocytes with a compound having a structure whereinA is purine; X is selected from the group consisting of CHRb, CH2CHRb, and CH&boxH;C(Rb); Y is selected from the group consisting of S, SO, and SO2; R1 and R2, independently, are selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, halo, NHC(&boxH;O)C1-3alkyleneN(Ra)2, NO2, ORa, OCF3, N(Ra)2, CN, OC(&boxH;O)Ra, C(&boxH;O)Ra, C(&boxH;O)ORa, arylORb, Het, NRaC(&boxH;O)C1-3alkyleneC(&boxH;O)ORa, arylOC1-3alkyleneN(Ra)2, arylOC(&boxH;O)Ra, C1-4alkyleneC(&boxH;O)ORa, OC1-4alkyleneC(&boxH;O)ORa, C1-4alkyleneOC1-4alkyleneC(&boxH;O)ORa, C(&boxH;O)NRaSO2Ra, C1-4alkyleneN(Ra)2, C2-6alkenyleneN(Ra)2, C(&boxH;O)NRaC1-4alkyleneORa, C(&boxH;O)NRaC1-4alkyleneHet, OC2-4alkyleneN(Ra)2, OC1-4alkyleneCH(ORb)CH2N(Ra)2, OC1-4alkyleneHet, OC2-4alkyleneORa, OC2-4alkyleneNRaC(&boxH;O)ORa, NRaC1-4alkyleneN(Ra)2, NRaC(&boxH;O)Ra, NRaC(&boxH;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(&boxH;O)N(Ra)2, NHC(&boxH;O)C1-C3alkylenearyl, C3-8cycloalkyl, C3-8heterocycloalkyl, arylOC1-3alkyleneN(Ra)2, arylOC(&boxH;O)Rb, NHC(&boxH;O)C1-3alkyleneC3-8heterocycloalkyl, NHC(&boxH;O)C1-3alkyleneHet, OC1-4alkyleneOC1-4alkyleneC(&boxH;O)ORb, C(&boxH;O)C1-4alkyleneHet, and NHC(&boxH;O)haloC1-6alkyl; 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(&boxH;O)Ra, aryl, heteroaryl, C(&boxH;O)ORa, C(&boxH;O)N(Ra)2, C(&boxH;S)N(Ra)2, SO2Ra, SO2N(Ra)2, S(&boxH;O)Ra, S(&boxH;O)N(Ra)2, C(&boxH;O)NRaC1-4alkyleneORa, C(&boxH;O)NRaC1-4alkyleneHet, C(&boxH;O)C1-4alkylenearyl, C(&boxH;O)C1-4alkyleneheteroaryl, C1-4alkylenearyl substituted with one or more of SO2N(Ra)2, N(Ra)2, C(&boxH;O)ORa, NRaSO2CF3, CN, NO2, C(&boxH;O)Ra, ORa, C1-4alkyleneN(Ra)2, and OC1-4alkyleneN(Ra)2, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(&boxH;O)C1-4alkylenearyl, C1-4alkyleneC(&boxH;O)C1-4alkyleneheteroaryl, C1-4alkyleneC(&boxH;O)Het, C1-4alkyleneC(&boxH;O)N(Ra)2, C1-4alkyleneORa, C1-4alkyleneNRaC(&boxH;O)Ra, C1-4alkyleneOC1-4alkyleneORa, C1-4alkyleneN(Ra)2, C1-4alkyleneC(&boxH;O)ORa, and C1-4alkyleneOC1-4alkyleneC(&boxH;O)ORa; Ra is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-3alkyleneN(Ra)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, and aryl; Het is 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(&boxH;O)ORa; and pharmaceutically acceptable salts and solvates, in an amount sufficient to inhibit phosphatidylinositol 3-kinase delta activity in said leukocytes.