NOVEL COMPOUNDS AND THERAPEUTIC USE THEREOF FOR PROTEIN KINASE INHIBITION

摘要

Novel compound having the following formula:;;wherein Y is N, O, or S. Also disclosed are a pharmaceutical compositions comprising the same, methods for treating cancer using the same, and methods for the synthesis of the same. The novel compounds of the present invention are found to inhibit protein kinases, especially Checkpoint kinase Chk1/Chk2.

主权项

1. A compound of formula I:wherein
Y=NH, O, or S, R1=selected from following groups:wherein X=CH2, NH, S, or O,
R8=—H, —NH2, —OH, —N(R4, R5), —C(R4R5)1-7NR6R7, —C(R4R5)1-7OR6, or —N(R4)NR5R6, wherein R4, R5, R6, R7═H, alkyls (C1-C6), cycloalkyls (C3-C8) with or without nuclear heteroatoms such as O, S, and N, aryls (either unsubstituted or substituted aromatics), or heteroaromatics (either unsubstituted or substituted heteroaromatics), R9, R10, R11, R12, and R13═H, alkyls (C1-C6), cycloalkyls (C3-C8) with or without nuclear heteroatoms such as O, S or N; aryls (either unsubstituted and substituted aromatics), or heteroaromatics (either unsubstituted or substituted heteroaromatics), R2, is selected from a group consisting of H, OH, NH2, OR14, NR14R15, alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heterocyclyl, heterocyclylalkyl, alkenyl, and alkynyl,wherein R14, R15═H, alkyls (C1-C6), cycloalkyls (C3-C8) with or without nuclear heteroatoms such as O, S, N, aryls (either unsubstituted or substituted aromatics), or heteroaromatics (either unsubstituted or substituted heteroaromatics),and
R3 is selected from a group consisting of H, alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heterocyclyl, heterocyclylalkyl, alkenyl, and alkynyl. Specifically R3 is selected from the following groups:wherein R16, R17, and R18 are selected from following groups: H; heteroatom such as F, Cl, Br, I; alkyl(C1-C8); cycloalkyl(C3-C8) without or with substitutions, wherein a substitution is selected from the group consisting of alkyls (C1-C8), cycloalkyls (C3-C8), aryls, heteroaryls; —OR19; —SR19; —NR19R20; —S(O)R19; —S(O)2R19; —S(O)2NR19R20; —C(O)NR19R20; —N(R19)C(O)R20; —N(R19)S(O)2R20; —N(R19)C(O)N(R20R21); N(R19)C(O)OR20; aryl with or without substitution, heteroaryl with or without substitution, aryalkyl with or without substitution, heterocyclyl with or without substitution, heterocyclylalkyl with or without substitution; alkenyl with or without substitution, and alkynyl with or without substitution;where R19, R20, and R21 are independently chosen from H, alkyl(C1-C8), cycloalkyls (C3-C8), aryl with or without substitution, alkylaryl with or without substitutions, heteroaryl with or without substitution,or R16, R17, and R21 can be part of a fused ring containing 0-3 heteroatoms selected from N, O, and S.