[1,2,4] triazol [4,3-A] pyridine derivative, preparation method therefor or medical application thereof
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.
1. A compound of formula (V) or a pharmaceutically acceptable salt thereof:
wherein:
R 2 is selected from the group consisting of hydrogen and fluorine;
W is selected from the group consisting of CH 2 , O, N and S;
R 15 and R 16 are each independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl and alkoxyl;
R 17 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxyl, C 1 -C 6 alkoxylalkyl, —C(O)R 5 , C 3 -C 10 cycloalkyl and 3 to 8-membered heterocyclyl;
R 5 is selected from the group of hydrogen, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, 3 to 8-membered heterocyclyl, C 2 -C 6 alkenyl, C 2 -C 6 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 of alkyl, halogen, hydroxy, amino, alkoxyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n C(O)OR 8 , —C(O)NR 9 R 10 , —NHC(O)R 8 , —NR 9 R 10 , —NHC(O)NR 9 R 10 , —NHC(O)OR 8 and —NHS(O) m R 8 ; and
m=0 or 1.
2. A compound selected from the group consisting of:
a pharmaceutically acceptable salt thereof.
3. A process for preparing the compound of formula (I) or the pharmaceutically acceptable salt thereof, wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is a compound of formula (V) of a pharmaceutically acceptable salt thereof according to claim 1 , the process comprising a step of:
reacting a compound of formula (IA) with a compound of formula (TB) under an alkaline condition to give the compound of formula (I) or the pharmaceutically acceptable salt thereof,
wherein R 1 is
R 2 is selected from group consisting of hydrogen and fluorine;
R 3 and R 4 are taken together with the attached carbon atoms to form the following structure:
and
m, W R 15 , R 16 , and R 17 are as defined in claim 1 .
4. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (V) or the pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier or excipient.
5. A method of modulating catalytic activity of a protein kinase, the method comprising a step of contacting the protein kinase with the compound of formula (V) or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the protein kinase is selected from the group consisting of c-Met tyrosine kinase.
6. The compound of formula (V) or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:
W is O;
R 15 and R 16 are each hydrogen;
R 17 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 1 -C 6 alkoxylalkyl; and
m is 1.
7. The compound according to claim 2 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to claim 2 , and a pharmaceutically acceptable carrier or excipient.
9. A method of modulating catalytic activity of a protein kinase, the method comprising a step of contacting the protein kinase with the compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein the protein kinase is selected from the group consisting of c-Met tyrosine kinase.