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US 2017/0247392 A1Published application
Alk kinase inhibitor, and preparation method and uses thereof
AssigneeBeijing Pearl Biotechnology Limited Liability Company
InventorsJiaqiang DONG, Boyu ZHONG, Hongbin YUAN, Chuan SHIH, Shaosong CHU, Deyi ZHANG, Ruihao ZHANG
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Abstract
An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.
Claims21
A compound of Formula I or pharmaceutically acceptable salts thereof,
- wherein,
- R1 is alkyl, haloalkyl or —O—R4, wherein R4 is hydrogen, C1-8 alkyl, halo C1-8 alkyl, C3-8 cycloalkyl, halo C3-8 cycloalkyl, C1-8 alkyl-C3-8 cycloalkyl, C3-8 cycloalkyl-C1-8 alkyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heterocyclyl -C1-8 alkyl;
- R2 is alkyl, cycloalkyl, heterocycloalkyl or heterocycloalkenyl, which may optionally be substituted with 1 to 3 substituents independently selected from the group consisting of oxo, C1-8 alkyl, halo C1-8 alkyl, C1-8 alkoxy, halo C1-8 alkoxy, C3-8 cycloalkyl, halo C3-8 cycloalkyl, C3-8 cycloalkoxy, halo C3-8 cycloalkoxy, C1-8 alkoxy-C1-8 alkyl, hydroxy-C1-8 alkyl, amino-C1-8 alkyl, carboxy -C1-8 alkyl, C1-8 alkyl-amino-C1-8 alkyl, halogen, hydroxy, cyano, cyano-C1-8 alkyl, amino, C1-8 alkyl-amino, di (C1-8 alkyl)-amino, C3-8 cycloalkyl amino, substituted or unsubstituted aromatic group, substituted or unsubstituted heteroaromatic group, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclyl-alkyl, (CH2)nCONR5R6, —COR5, —SO2R5 and —NR5SO2R6, wherein n is an integer of 0-8, R5 and R6 are independently hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, amino, C1-8 alkyl-amino, di (C1-8 alkyl)-amino, cyano-C1-8 alkyl, C1-8 alkyl-amino-C1-8 alkyl or di (C1-8 alkyl)-amino-C1-8 alkyl, wherein the substituents may optionally form a ring with the carbon atoms to which they are attached;
- R3 is —SO2R7, —SO2NR7R8, —CN, —CONR7R8, or —COR7, wherein R7 and R8 are independently hydrogen, alkyl or cycloalkyl;
- X is a chemical bond, O, S, CO, NR9, SO2 or S(O), wherein R9 is hydrogen, C1-8 alkyl, halo C1-8 alkyl, C3-8 cycloalkyl, halo C3-8 cycloalkyl, C1-8 alkyl-CO or 4-6 membered heterocyclyl;
- Z1 is N or C—R10 , wherein R10 is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy or cyano;
- Z2 is C—R11 or N, wherein R11 is hydrogen, C1-8 alkyl, halo C1-8 alkyl, C3-8 cycloalkyl, halo C3-8 cycloalkyl, C1-8 alkoxy, halo C1-8 alkoxy, C3-8 cycloalkoxy, halo C3-8 cycloalkoxy, halogen, amino, C1-8 alkyl-amino, di(C1-8 alkyl)-amino or cyano, wherein R11 and R2 may optionally form a ring together with the carbon atoms to which they are attached, the ring may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of oxo, C1-8 alkyl, halo C1-8 alkyl, C1-8 alkoxy, halo C1-8 alkoxy, C3-8 cycloalkyl, halo C3-8 cycloalkyl, C3-8 cycloalkoxy, halo C3-8 cycloalkoxy, C1-8 alkoxy-C1-8 alkyl, hydroxy-C1-8 alkyl, amino-C1-8 alkyl, carboxy-C1-8 alkyl, C1-8 alkyl-amino-C1-8 alkyl, halogen, hydroxy, cyano, cyano-C1-8 alkyl, amino, C1-8 alkyl-amino, di(C1-8 alkyl)-amino, C3-8 cycloalkyl-amino, substituted or unsubstituted aromatic group, substituted or unsubstituted heteroaromatic group, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclyl alkyl, (CH2)nCONR12R13, —COR12, —SO2R12 and —NR12SO2R13, wherein n is an integer of 0-8, R12 and R13 are independently hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, amino, C1-8 alkyl-amino, di(C1-8 alkyl)-amino, cyano-C1-8 alkyl, C1-8 alkyl-amino-C1-8 alkyl or di(C1-8 alkyl)-amino-C1-8 alkyl;
- Z3, Z4 and Z5are selected from the following groups:
- Z3 is N, Z4 is N—R14, Z5 is CH or N;
- Z3 is N, Z4 is C—R14, Z5 is N, O or S;
- Z3 is O or S, Z4 is N—R14, Z5 is CH;
- Z3 is O or S, Z4 is C—R14, Z5 is N;
- and
- Z3 is C, Z4 is N—R14, Z5is O or S;
- wherein R14 is hydrogen, alkyl, haloalkyl, C3-8 cycloalkyl, halo-C3-8 cycloalkyl or 4-6 membered heterocyclyl.
12 more elements
Dependencies are inferred from the claim text.