PURINE DERIVATIVES

摘要

The present invention relates to compounds of formula (I);;or pharmaceutically acceptable salts thereof, wherein Q, G, ring A, ring B, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, and m are defined herein. The novel purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

主权项

1. A compound of formula (I):wherein
R1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 4-6 membered heterocycloalkyl, or 4-6 membered heteroaryl, wherein the C1-C6 alkyl is optionally substituted by one, two or three substituents selected from the group consisting of halogen, hydroxy, and C1-C3 alkoxy, further wherein the C3-C6 cycloalkyl, the 4-6 membered heterocycloalkyl, and the 4-6 membered heteroaryl are each independently optionally substituted by one, two or three substituents selected from the group consisting of C1-C3 alkyl, hydroxy, and C1-C3 alkoxy; ring A is C6-C10 aryl or 5-12 membered heteroaryl; R2 and R5 are each independently absent, hydrogen, halogen, cyano, difluoromethyl, trifluoromethyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, —N(R10)(R11), C3-C5 cycloalkyl, or 4-6 membered heterocycloalkyl, wherein the C1-C6 alkyl is optionally substituted by one, two or three substituents selected from the group consisting of halogen, hydroxy, C1-C6 alkoxy, and —N(R12)(R13); R3 is absent, hydrogen, halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C7 cycloalkyl, or 3-7 membered heterocycloalkyl, wherein the C1-C6 alkyl and the C1-C6 alkoxy are each optionally substituted by one, two or three R14 groups, and further wherein the C3-C7 cycloalkyl and the 3-7 membered heterocycloalkyl are each optionally substituted by one, two or three R15 groups; R4 is absent, hydrogen, halogen, C1-C6 alkyl, or C3-C6 cycloalkyl, wherein R2 and R3 or R3 and R4 may combine to form a C5-C7 cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, further wherein the C5-C7 cycloalkyl ring and the 5-7 membered heterocycloalkyl ring are each independently optionally substituted by one, two or three R14 groups; Q is absent, O, S, or NR9; ring B is absent, C3-C10 cycloalkyl, 3-10 membered heterocycloalkyl, C6-C10 aryl, or 5-12 membered heteroaryl; R6 and R8 are each independently absent, hydrogen, halogen, cyano, hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkyl, C1-C3 alkoxy, or C3-C5 cycloalkyl, wherein the C1-C3 alkyl is optionally substituted by hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkoxy, or C3-C5 cycloalkyl; R7 is G is absent when the attachment point of R7 on ring B is a nitrogen atom, and G is —NR18— when ring B is absent or when the attachment point of R7 on ring B is a carbon atom; R9, R12 and R13 are each independently hydrogen or C1-C3 alkyl; R10 and R11 are each independently hydrogen or C1-C6 alkyl; or R10 and R11 together with the nitrogen to which they are attached, may combine to form a 4-7 membered heterocycloalkyl ring, when R10 and R11 are each C1-C3 alkyl, wherein the 4-7 membered heterocycloalkyl ring formed is optionally substituted by one, two, three or four R15 groups; each R14 is independently halogen, cyano, C1-C3 alkyl, hydroxy, C1-C6 alkoxy, —N(R19)(R20), —CON(R21)(R22), or 3-7 membered heterocycloalkyl, wherein the 3-7 membered heterocycloalkyl is optionally substituted by one, two, three or four R15 groups; each R15 is independently halogen, C1-C3 alkyl, hydroxy, C1-C6 alkoxy, —NH2, —NHCH3, or —N(CH3)2; R16 and R17 are each independently hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted by —N(R23)(R24), provided that R16 and R17 may form a C3-C5 cycloalkyl ring; R18 is hydrogen or C1-C3 alkyl; each R19, R20, R21, R22, R23, and R24 is independently hydrogen or C1-C3 alkyl; and m is 0, 1 or 2, provided that when ring B is absent, m is 2; or a pharmaceutically acceptable salt thereof.