[1,2,4] TRIAZOL [4,3-A] PYRIDINE DERIVATIVE, PREPARATION METHOD THEREFOR OR MEDICAL APPLICATION THEREOF

摘要

Provided are [1,2,4]triazol[4,3-a]pyridine derivatives as shown in the general formula (I), a preparation method therefor, and a pharmaceutical composition containing the derivative, wherein the pharmaceutical composition is used as a therapeutic agent, and especially used as a c-Met inhibitor and an immunosuppressant. Each substituent in the general formula (I) is the same as that defined in the specification.;

主权项

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein:
R1 is selected from the group consisting of pyrazolyl, alkyl, cycloalkyl, haloalkyl, alkoxyl, aryl, heteroaryl and heterocyclyl, optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, alkyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)nC(O)OR5, —C(O)NR6R7, —NHC(O)R5, —NR6R7, —NHC(O)NR6R7, —NHC(O)(O)R5 and —NHS(O)mR5; R2 is selected from the group consisting of hydrogen, halogen, C1-C6alkoxyl and haloC1-C6alkoxyl; R3 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6alkoxyl, haloC1-C6alkoxyl, 3 to 8-membered heterocyclyl, —NHR8 and NR8R9, optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, alkyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)nC(O)OR5, —C(O)NR6R7, —NHC(O)R5, —NR6R7, —NHC(O)NR6R7, —NHC(O)(O)R5 and —NHS(O)mR5; R4 is selected from the group consisting of hydrogen, pyrazolyl, C1-C6 alkyl, C3-C10cycloalkyl, C1-C6alkoxyl, aryl, heteroaryl, 3 to 8-membered heterocyclyl, —NHR8 and NR8R9, optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, alkyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)nC(O)OR5, —C(O)NR6R7, —NHC(O)R5, —NR6R7, —NHC(O)NR6R7, —NHC(O)(O)R5 and —NHS(O)mR5; or R3 and R4 are taken together with the attached carbon atoms to form a C5-C10 aliphatic ring, heterocyclyl comprising 1 to 3 heteroatoms selected from the group consisting of O, N and S, lactone, lactam, thiolactam, urea orthiourea, optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, alkyl, alkoxyl, alkoxylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R5, —C(O)NR6R7, —NHC(O)R5, —NR6R7, —OC(O)NR6R7, —NHC(O)NR6R7, —NHC(O)(O)R5 and —NHS(O)mR5; R5 is selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C10cycloalkyl, 3 to 8-membered heterocyclyl, C2-C6alkenyl, C2-C6 alkynyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups independently selected from the group consisting of alkyl, halogen, hydroxy, amino, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)nC(O)OR8, —C(O)NR9R10, —NHC(O)R8, —NR9R10, —NHC(O)NR9R10, —NHC(O)OR8 and —NHS(O)mR8; R6 and R7 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C10cycloalkyl, 3 to 8-membered heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each optionally substituted by one or more groups independently selected from the group consisting of alkyl, halogen, hydroxy, amino, alkoxyl, cycloalkyl, heterocyclyl, hydroxyalkyl, alkynyl, aryl, heteroaryl and —OR8; R8 is selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6alkoxyl, 3 to 8-membered heterocyclyl, hydroxyalkyl, aryl and heteroaryl; R9 and R10 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C10cycloalkyl, 3 to 8-membered heterocyclyl, aryl and heteroaryl; and m and n are each independently selected from 0, 1 and 2.