Inhibitors of human phosphatidylinositol 3-kinase delta

A compound of formula (I):

• wherein A is an optionally substituted
• where A can be substituted with up to three substituents selected from N(Ra)2, halo, C1-3alkyl, S(C1-3alkyl), ORa, and
• X is selected from CH2, CH(CH3), CH(CH2CH3), and C(CH3)2;
• Y is selected from the group consisting of null, and NH;
• R1 and R2, independently, are selected from the group consisting of hydrogen, C1-6alkyl, ORa, CF3, NO2, N(Ra)2, halo, NRa—C1-3alkylene-N(Ra)2, and OC1-3alkylene-ORa;
• R3 is selected from the group consisting of
• each of which is optionally substituted with up to three substituents selected from the group consisting of Cl, F, CH3, CH(CH3)2, OH, OCH3, OCH2C6H5, O(CH2)3N(CH3)2, OCH2C═CH, OCH2C(═O)NH2, C6H5, NO2, NH2, NHC(═O)CH3, CO2H, N(CH3)CH2CH2N(CH3)2, and
• each Ra is independently selected from the group consisting of hydrogen and C1-6alkyl;
• or two Ra groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom;
• or a pharmaceutically acceptable salt thereof.

A compound selected from the group consisting of:

• 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)-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;
• and pharmaceutically acceptable salts thereof.

A compound selected from the group consisting of:

• 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-(6-aminopurin-9-ylmethyl)-3-(2-(3-dimethylamino-propoxy)-phenyl)-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;
• and
• 2-(2-benzyloxy-1-(9H-purin-6-ylamino)ethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one;
• and pharmaceutically acceptable salts thereof.

A pharmaceutical composition comprising:

• a):
• an effective amount of a compound of formula (I):
• wherein A is an optionally substituted purinyl ring system;
• X is C(Rb)2;
• Y is selected from the group consisting of null and NH;
• R1 and R2, independently, are selected from the group consisting of hydrogen, N(Ra)2, halo, C1-3alkyl, S(C1-3alkyl), and ORa;
• R3 is selected from the group consisting of optionally substituted aryl and heteroaryl;
• each Ra is independently selected from the group consisting of hydrogen and C1-6alkyl;
• or two Ra groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom;
• and
• each Rb is independently selected from the group consisting of hydrogen and C1-6alkyl;
• and pharmaceutically acceptable salts thereof;
• and
• b):
• a pharmaceutically acceptable excipient.

A pharmaceutical composition comprising:

• a) an effective amount of a compound of formula (I):
• wherein A is an optionally substituted
• where A can be substituted with up to three substituents selected from N(Ra)2, halo, C1-3alkyl, S(C1-3alkyl), ORa, and
• X is selected from CH2, CH(CH3), CH(CH2CH3), and C(CH3)2;
• Y is selected from the group consisting of null, and NH;
• R1 and R2, independently, are selected from the group consisting of hydrogen, methyl, ORa, CF3, NO2, N(Ra)2, halo, NRa—C1-3alkylene-N(Ra)2, and OC1-3alkylene-ORa;
• R3 is selected from the group consisting of
• each of which is optionally substituted with up to three substituents selected from the group consisting of Cl, F, CH3, CH(CH3)2, OH, OCH3, OCH2C6H5, O(CH2)3N(CH3)2, OCH2C═CH, OCH2C(═O)NH2, C6H5, NO2, NH2, NHC(═O)CH3, CO2H, N(CH3)CH2CH2N(CH3)2, and
• each Ra is independently selected from the group consisting of hydrogen and C1-6alkyl;
• or two Ra groups are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom;
• or a pharmaceutically acceptable salt thereof.