5-AZAINDAZOLE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS
The present invention relates to novel 5-azaindazole derivatives of formula (I), as described and defined herein, and pharmaceutically acceptable salts, solvates and prodrug thereof, as well as pharmaceutical compositions comprising such compounds. The 5-azaindazole derivatives according to the invention have been found to be highly effective dual A 2A /A 2B adenosine receptor antagonists, and can thus be used as therapeutic agents, particularly in the treatment or prevention of hyperproliferative or infectious diseases or disorders.
1 . A compound of formula (I)
wherein:
R 1A and R 1B are mutually linked to form, together with the nitrogen atom that they are attached to, a heterocycloalkyl which is optionally substituted with one or more groups R 11 ;
or, alternatively, R 1A and R 1B are each independently selected from hydrogen, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —CO(C 1-5 alkyl), carbocyclyl, and heterocyclyl, wherein said alkyl, said alkenyl, said alkynyl, and the alkyl moiety of said —CO(C 1-5 alkyl) are each optionally substituted with one or more groups R 12 , and further wherein said carbocyclyl and said heterocyclyl are each optionally substituted with one or more groups R 13 ;
each R 11 is independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—NH—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —NH—CO—O—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —O—CO—NH—(C 1-5 alkyl), —O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;
each R 12 is independently selected from —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —NH—CO—O—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —O—CO—NH—(C 1-5 alkyl), —O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;
each R 13 is independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—NH—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-cycloalkyl, and —(C 0-3 alkylene)-heterocycloalkyl;
R 2 and R 4 are each independently selected from hydrogen, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—NH—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —NH—CO—O—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —O—CO—NH—(C 1-5 alkyl), —O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;
R 3 is selected from hydrogen, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 1-5 alkylene)-OH, —(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 1-5 alkylene)-O(C 1-5 alkylene)-OH, —(C 1-5 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 1-5 alkylene)-SH, —(C 1-5 alkylene)-S(C 1-5 alkyl), —(C 1-5 alkylene)-NH 2 , —(C 1-5 alkylene)-NH(C 1-5 alkyl), —(C 1-5 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 1-5 alkylene)-halogen, C 1-5 haloalkyl, —(C 1-5 alkylene)-O—(C 1-5 haloalkyl), —(C 1-5 alkylene)-CF 3 , —(C 1-5 alkylene)-CN, —(C 1-5 alkylene)-NO 2 , —(C 1-5 alkylene)-Si(C 1-5 alkyl) 3 , —(C 1-5 alkylene)-O(C 1-5 alkylene)-Si(C 1-5 alkyl) 3 , —(C 1-5 alkylene)-CHO, —(C 1-5 alkylene)-CO—(C 1-5 alkyl), —(C 1-5 alkylene)-COOH, —(C 1-5 alkylene)-CO—O—(C 1-5 alkyl), —(C 1-5 alkylene)-O—CO—(C 1-5 alkyl), —(C 1-5 alkylene)-CO—NH 2 , —(C 1-5 alkylene)-CO—NH(C 1-5 alkyl), —(C 1-5 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 1-5 alkylene)-NH—CO—(C 1-5 alkyl), —(C 1-5 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 1-5 alkylene)-NH—CO—O—(C 1-5 alkyl), —(C 1-5 alkylene)-N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —(C 1-5 alkylene)-O—CO—NH—(C 1-5 alkyl), —(C 1-5 alkylene)-O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —(C 1-5 alkylene)-SO 2 —NH 2 , —(C 1-5 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 1-5 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 1-5 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 1-5 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 1-5 alkylene)-SO—(C 1-5 alkyl), —(C 1-5 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-5 alkylene)-carbocyclyl, and —(C 0-5 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-5 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-5 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —NH—CO—O—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —O—CO—NH—(C 1-5 alkyl), —O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;
ring A is a bicyclic heteroaryl, wherein said bicyclic heteroaryl is optionally substituted with one or more groups R A ; and
each R A is independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—NH—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —NH—CO—O—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—O—(C 1-5 alkyl), —O—CO—NH—(C 1-5 alkyl), —O—CO—N(C 1-5 alkyl)-(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.
2 . The compound of claim 1 , wherein R 1A and R 1B are mutually linked to form, together with the nitrogen atom that they are attached to, a heterocycloalkyl which is optionally substituted with one or more groups R 11 .
3 . The compound of claim 1 , R 1A and R 1B are mutually linked to form, together with the nitrogen atom that they are attached to, a group which is selected from
wherein each one of the above-depicted groups is optionally substituted with one or more R 11 .
4 . The compound of claim 1 , wherein R 2 and R 4 are each independently selected from hydrogen, C 1-5 alkyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —CF 3 , and —CN.
5 . The compound of claim 1 , wherein R 3 is selected from C 1-5 haloalkyl, —(C 1-5 alkylene)-CN, —(C 1-5 alkylene)-SO—(C 1-5 alkyl), and —(C 1-5 alkylene)-SO 2 —(C 1-5 alkyl).
6 . The compound of claim 1 , wherein R 3 is —CH 2 —CF 3 or —CH 2 —SO 2 —CH 3 .
7 . The compound of claim 1 , wherein ring A is a fused bicyclic heteroaryl, wherein one of the two fused rings of said fused bicyclic heteroaryl has 5 ring atoms and the other fused ring has 6 ring atoms, and further wherein said bicyclic heteroaryl is optionally substituted with one or more groups R A .
8 . The compound of claim 1 , wherein ring A is a bicyclic heteroaryl having the following formula (II):
wherein each of the two fused rings of said bicyclic heteroaryl is aromatic,
wherein each ring atom A of the bicyclic heteroaryl is independently a carbon or nitrogen atom, wherein each ring atom B is independently a carbon, nitrogen, oxygen or sulfur atom, wherein at least one of the ring atoms A and/or B is different from carbon, and wherein said bicyclic heteroaryl is optionally substituted with one or more groups R A .
9 . The compound of claim 1 , wherein ring A is selected from any one of the following groups:
wherein each of the above-depicted groups is optionally substituted with one or more groups R A ;
and preferably wherein ring A is selected from any one of the following groups:
wherein each of the above-depicted groups is optionally substituted with one or more groups R A .
10 . The compound of claim 1 , wherein each R A is independently selected from C 1-5 alkyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —CF 3 , and —CN; preferably wherein each R A is independently halogen; and more preferably wherein each R A is —F.
11 . The compound of claim 1 , wherein said compound is selected from:
1
[3-(1-Methyl-1H-indol-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridine-6-yl]-1,4-oxazepan-4-yl-methanone
2
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2-
methanesulfonyl-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
3
Azepan-1-yl-[1-(2,2-difluoro-ethyl)-3-(6-fluoro-imidazo[1,2-
a]pyridin-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
4
Azepan-1-yl-[1-(2-fluoro-ethyl)-3-(6-fluoro-imidazo[1,2-
a]pyridin-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methenone
5
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-propyl-
1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
6
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methoxymethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
7
[6-(Azepane-1-carbonyl)-3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-
pyrazolo[4,3-c]pyridin-1-yl]-acetonitrile
8
Azepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2-
methoxy-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
9
[1-Cyclopropylmethyl-3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-
yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-4-yl-methanone
10
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-methanesulfonyl-
1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-4-yl-methanone
11
3-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-6-(1,4-oxazepane-
4-carbonyl)-pyrazolo[4,3-c]pyridin-1-ylmethyl]-azetidine-1-
carboxylic acid tert-butyl ester
12
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-hydroxymethyl-
1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-4-yl-methanone
13
[3-Benzofuran-3-yl-6-(1,4-oxazepane-4-carbonyl)-pyrazolo[4,3-
c]pyridin-1-yl]-acetonitrile
14
(3-Aza-bicyclo[3.2.1]oct-3-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-methylsulfanylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
15
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-
oxazepan-4-yl-methanone
16
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridine-6-yl)-1,4-oxazepan-4-yl-methanone
17
(1-Methanesulfonylmethyl-3-pyrazolo[1,5-a]pyridin-3-yl-1H-
pyrazolo[4,3-c]pyridin-6-yl)-1,4-oxazepan-4-yl-methanone
18
(3-Aza-bicyclo[3.2.1]oct-3-yl)-(1-methanesulfonylmethyl-3-
pyrazolo[1,5-a]pyridin-3-yl-1H-pyrazolo[4,3-c]pyridin-6-yl)-
methanone
19
(3-Aza-bicyclo[3.2.1]oct-3-yl)-(3-benzofuran-3-yl-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-
methanone
20
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
21
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfinylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
22
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
ethanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-
oxazepan-4-yl-methanone
23
(3-Aza-bicyclo[3.2.1]oct-3-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
24
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-endo-
hydroxy-8-exo-methyl-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone
25
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-
hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone
26
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-oxa-5-
aza-bicyclo[2.2.1]hept-5-yl)-methanone
27
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
methanesulfonylmethyl-1H-pyrazolo[4,3 c]pyridin-6-yl]-(8-oxa-3-
aza-bicyclo[3.2.1]oct-3-yl)-methanone
28
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(8-endo-hydroxy-8-exo-methyl-d3-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
29
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(6,6-difluoro-1,4-oxazepan-4-yl)-methanone
30
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(8-endo-hydroxy-3-aza-bicyclo[3.2.1]oct-3-yl)-
methanone
31
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(5-endo-hydroxy-5-exo-methyl-2-aza-
bicyclo[2.2.1]hept-2-yl)-methanone
32
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone
33
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(4,4-difluoro-piperidin-1-yl)-methanone
34
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(2-methoxymethyl-pyrrolidin-1-yl)-methanone
35
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(4-hydroxy-2,2 dimethyl-piperidin-1-yl)-
methanone
36
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(4-hydroxy-piperidin-1-yl)-methanone
37
[3-(benzofuran-3-yl)-1-(methylsulfonylmethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-
yl)methanone
38
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(3-hydroxy-piperidin-1-yl)-methanone
39
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(3,3-difluoro-piperidin-1-yl)-methanone
40
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridin-6-yl)-(4-hydroxyazepan-1-yl)-methanone
41
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-methyl-
1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
42
3-[6-(Azepane-1-carbonyl)-1-methyl-1H-pyrazolo[4,3-c]pyridin-3-
yl]-imidazo[1,2-a]pyridine-6-carbonitrile
43
3-[6-(Azepane-1-carbonyl)-1-propyl-1H-pyrazolo[4,3-c]pyridin-3-
yl]-imidazo[1,2-a]pyridine-6-carbonitrile
44
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
45
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carbonitrile
46
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]-pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carboxylic
acid amide
47
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-8-methyl-imidazo[1,2-a]pyridine-6-
carbonitrile
48
Azepan-1-yl-[3-(6-chloro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
49
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carboxylic
acid methylamide
50
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyrimidin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
51
Azepan-1-yl-[3-(6-methoxymethyl-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
52
Azepan-1-yl-[3-indolizin-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
53
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carboxylic
acid dimethylamide
54
Azepan-1-yl-[3-imidazo[1,5-a]pyridin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
55
Azepan-1-yl-[3-imidazo[1,2-a]pyridin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
56
Azepan-1-yl-[3-imidazo[1,2-a]pyrazin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
57
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-7-methyl-imidazo[1,2-a]pyridine-6-
carboxylic acid amide
58
Azepan-1-yl-[1-(2,2,2-trifluoro-ethyl)-3-(6-trifluoromethyl-
imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
59
Azepan-1-yl-[3-(6-methoxy-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
60
Azepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
61
Azepan-1-yl-[3-(6-methyl-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
62
Azepan-1-yl-[3-(8-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
63
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-7-hydroxy-imidazo[1,2-a]pyridine-6-
carbonitrile
64
Azepan-1-yl-[3-[6-(1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-3-yl]-
1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
65
Azepan-1-yl-[3-(6-cyclopropyl-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
66
Azepan-1-yl-[1-(2,2,2-trifluoro-ethyl)-3-(6-trifluoromethoxy-
imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
67
Azepan-1-yl-[3-(7-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
68
Azepan-1-yl-[3-(6-hydroxy-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
69
Azepan-1-yl-[3-(6-difluoromethyl-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
70
Azepan-1-yl-[3-[6-(2,2,2-trifluoro-ethoxy)-imidazo[1,2-a]pyridin-
3-yl]-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
71
Azepan-1-yl-[3-[1,2,4]triazolo[4,3-a]pyridin-3-yl-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
72
Azepan-1-yl-[3-[6-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-
a]pyridin-3-yl]-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
73
Azepan-1-yl-[3-(7-chloro-6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
74
Azepan-1-yl-[3-(6-chloro-7-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
75
Azepan-1-yl-[3-(6-chloro-7-hydroxy-imidazo[1,2-a]pyridin-3-yl)-
1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
76
Azepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2-
trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
77
Azepan-1-yl-[3-(6-fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2-
trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
78
Azepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(4-
methoxy-benzyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
79
Azepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
(tetrahydro-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
80
[3-(6-Fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-
1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-4-yl-methanone
81
3-[6-(1,4-Oxazepane-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carbonitrile
82
[3-(6-Fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-
1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-
yl)-methanone
83
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3c]pyridin-6-yl]-(8-oxa-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
84
3-[6-(8-Oxa-3-aza-bicyclo[3.2.1]octane-3-carbonyl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-
a]pyridine-6-carbonitrile
85
[3-(8-fluoroimidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-hydroxy-8-
azabicyclo[3.2.1]octan-8-yl)methanone
86
[3-(6-fluoroimidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-hydroxy-8-
azabicyclo[3.2.1]octan-8-yl)methanone
87
[3-(imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-hydroxy-8-
azabicyclo[3.2.1]octan-8-yl)methanone
88
(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-[3-(6-
hydroxyimidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
89
Azepan-1-yl-[3-pyrazolo[1,5-a]pyridin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone hydrochloride
90
Azepan-1-yl-[3-benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
91
Azepan-1-yl-[3-(1H-indol-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
92
Azepan-1-yl-[3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
93
1,4-Oxazepan-4-yl-[3-thieno[2,3-c]pyridin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
94
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridine-6-yl]-1,4-oxazepan-4-yl-methanone
95
1,4-Oxazepan-4-yl-[3-pyrazolo[1,5-a]pyridine-3-yl-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridine-6-yl]-methanone
96
[3-(1H-Indol-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridine-6-yl]-1,4-oxazepan-4-yl-methanone
97
1,4-Oxazepan-4-yl-[3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridine-6-yl]-methanone
98
[3-Benzo[b]thiophen-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridine-6-yl]-1,4-oxazepan-4-yl-methanone
99
(8-Oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-[3-pyrazolo[1,5-a]pyridin-3-
yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
100
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone
101
(3-Aza-bicyclo[3.2.1]oct-3-yl)-[3-benzofuran-3-yl-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
102
(3-Aza-bicyclo[3.2.1]oct-3-yl)-[3-pyrazolo[1,5-a]pyridin-3-yl-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
103
[3-Benzofuran-3-yl-1-(2,2-difluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-1,4-oxazepan-4-yl-methanone
104
[3-Benzofuran-3-yl-1-(2-fluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-
6-yl]-1,4-oxazepan-4-yl-methanone
105
2-[3-Benzofuran-3-yl-6-(1,4-oxazepane-4-carbonyl)-pyrazolo[4,3-
c]pyridin-1-yl]-acetamide
106
(3-Benzofuran-3-yl-1-propyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-1,4-
oxazepan-4-yl-methanone
107
(3-Benzofuran-3-yl-1-methanesulfonylmethyl-1H-pyrazolo[4,3-
c]pyridine-6-yl)-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone
108
(1-Methanesulfonylmethyl-3-pyrazolo[1,5-a]pyridine-3-yl-1H-
pyrazolo[4,3-c]pyridine-6-yl)-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-
yl)-methanone
109
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
110
[3-(5-fluorobenzofuran-3-yl)-1-
(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-
oxazepan-4-yl)methanone
111
[3-(5-fluorobenzofuran-3-yl)-1-
(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-(8-oxa-3-
azabicyclo[3.2.1]octan-3-yl)methanone
112
(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-[3-(1H-indol-3-
yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
113
(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-[3-pyrazolo[1,5-
a]pyridin-3-yl-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-
yl]methanone
114
(4-hydroxy-1-piperidyl)-[3-pyrazolo[1,5-a]pyridin-3-yl-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
115
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxy-1-piperidyl)methanone
116
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxy-4-methyl-1-piperidyl)methanone
117
(4-hydroxy-4-methyl-1-piperidyl)-[3-pyrazolo[1,5-a]pyridin-3-yl-
1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
118
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(6-hydroxy-1,4-oxazepan-4-yl)methanone
119
(6-hydroxy-1,4-oxazepan-4-yl)-[3-pyrazolo[1,5-a]pyridin-3-yl-1-
(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
120
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(6,6-dideuterio-1,4-oxazepan-4-yl)methanone
121
(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-pyrazolo[1,5-a]pyridin-3-yl-
1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
122
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxyazepan-1-yl)methanone
123
[3-(5-fluoro-1H-indol-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
124
methyl 3-[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-3-yl]benzofuran-5-
carboxylate
125
[3-(5-methylbenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
126
[3-(2-methylbenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
127
[3-(5-fluorobenzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone
128
3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carboxylic acid amide
129
3-[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-3-yl]benzofuran-5-carboxylic
acid
130
1-[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridine-6-carbonyl]piperidine-4-carboxylic acid
131
[3-(6-Fluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-
1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-piperidin-1-yl)-
methanone
132
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-piperidin-1-yl)-
methanone
133
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-4-methyl-
piperidin-1-yl)-methanone
134
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-hydroxy-azepan-1-yl)-
methanone
135
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-oxa-5-aza-
bicyclo[2.2.1]hept-5-yl)-methanone
136
[3-(6,8-Difluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-hydroxy-8-aza-
bicyclo[3.2.1]oct-8-yl)-methanone
137
[3-(6,8-Difluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-4-
yl-methanone
138
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-2-methyl-
piperidin-1-yl)-methanone
139
(3-Aza-bicyclo[3.2.1]oct-3-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
140
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(9-hydroxy-3-aza-
bicyclo[3.3.1]non-3-yl)-methanone
141
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-2-isopropyl-
piperidin-1-yl)-methanone
142
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-2,2-dimethyl-
piperidin-1-yl)-methanone
143
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-3-isobutyl-
piperidin-1-yl)-methanone
144
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-fluoro-piperidin-1-yl)-
methanone
145
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-oxa-2-aza-
spiro[4.5]dec-2-yl)-methanone
146
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4,4-difluoro-piperidin-1-
yl)-methanone
147
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4′-hydroxy-3′,4′,5′,6′-
tetrahydro-2′H-[3,4′]bipyridinyl-1′-yl)-methanone
148
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-4-
trifluoromethyl-piperidin-1-yl)-methanone
149
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-methoxymethyl-
pyrrolidin-1-yl)-methanone
150
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-methyl-1,4-diazepan-1-
yl)-methanone
151
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-hydroxy-piperidin-1-yl)-
methanone
152
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(7-oxa-2-aza-
spiro[4.5]dec-2-yl)-methanone
153
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-oxa-9-aza-
spiro[5.5]undec-9-yl)-methanone
154
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(tetrahydro-furo[3,4-
c]pyrrol-5-yl)-methanone
155
8-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-2,8-diaza-
spiro[4.5]decan-3-one
156
8-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-2,8-diaza-
spiro[4.5]decan-1-one
157
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-[3-(2-methoxy-ethyl)-
pyrrolidin-1-yl]-methanone
158
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-morpholin-4-yl-methanone
159
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3,3-difluoro-piperidin-1-
yl)-methanone
160
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3,3-difluoro-piperidin-1-
yl)-methanone
161
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-hydroxymethyl-
piperidin-1-yl)-methanone
162
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-endo-hydroxy-8-exo-
methyl-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone
163
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-trifluoromethyl-
morpholin-4-yl)-methanone
164
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-trifluoromethyl-
piperidin-1-yl)-methanone
165
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxymethyl-
piperidin-1-yl)-methanone
166
[3-(6,8-Difluoro-imidazo[l,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-oxa-7-aza-
spiro[3.5]non-7-yl)-methanone
167
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-methoxymethyl-
morpholin-4-yl)-methanone
168
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-hydroxy-8-aza-
bicyclo[3.2.1]oct-8-yl)-methanone
169
(4-Aza-tricyclo[4.3.1.1*3,8*]undec-4-yl)-[3-(6,8-difluoro-
imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
170
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-exo-hydroxy-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
171
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-exo-hydroxy-8-aza-
bicyclo[3.2.1]oct-8-yl)-methanone
172
(8-Aza-bicyclo[3.2.1]oct-8-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
173
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-difluoromethyl-
piperidin-1-yl)-methanone
174
3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carboxylic acid (2-hydroxy-2-
methyl-propyl)-amide
175
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-oxa-6-aza-
tricyclo[3.3.1.1*3,7*]dec-6-yl)-methanone
176
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxymethyl-4-
methyl-piperidin-1-yl)-methanone
177
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(4-hydroxy-azepan-1-yl)-
methanone
178
(2-Aza-tricyclo[3.3.1.1*3,7*]dec-2-yl)-[3-(6,8-difluoro-
imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
179
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(5-oxa-8-aza-
spiro[2.6]non-8-yl)-methanone
180
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-thiazepan-1,1-dioxide-
4-yl-methanone
181
Cis-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2,6-dimethyl-
morpholin-4-yl)-methanone
182
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2,2-dimethyl-1,4-
oxazepan-4-yl)-methanone
183
Cis-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3,5-dimethyl-
morpholin-4-yl)-methanone
184
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(3-oxa-8-aza-
bicyclo[3.2.1]oct-8-yl)-methanone
185
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(6,6-difluoro-1,4-
oxazepan-4-yl)-methanone
186
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-oxa-4-aza-
spiro[2.6]non-4-yl)-methanone
187
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-endo-hydroxy-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
188
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(7-endo-hydroxy-3-oxa-9-
aza-bicyclo[3.3.1]non-9-yl)-methanone
189
1-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-1,4-diazepan-5-one
190
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1,4-oxazepan-deuterium-4-
yl-methanone
191
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-[1,2]oxazepan-2-yl-
methanone
192
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(5-oxa-8-aza-
spiro[3.5]non-8-yl)-methanone
193
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(6-hydroxy-1,4-oxazepan-
4-yl)-methanone
194
5-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-2,5-diaza-
bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester
195
1,4-Diazepan-1-yl-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
196
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(8-oxa-5-aza-
spiro[3.5]non-5-yl)-methanone
197
(2-{[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-methyl-
amino}-ethyl)-carbamic acid tert-butyl ester
198
3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carboxylic acid (4-hydroxy-
tetrahydro-pyran-3-yl)-amide
199
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(6-oxa-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
200
3-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-3,8-diaza-
bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester
201
4-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-1,4-diazepan-2-one
202
{1-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trilluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-azepan-3-yl}-
carbamic acid tert-butyl ester
203
(3,3-Difluoro-4-hydroxy-piperidin-1-yl)-[3-(6,8-difluoro-
imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-6-yl]-methanone
204
{4-[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridine-6-carbonyl]-1,4-oxazepan-6-
yl}-carbamic acid tert-butyl ester
205
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(2-oxa-5-aza-
bicyclo[4.1.0]hept-5-yl)-methanone
206
[3-(6,8-Difluoro-imidazo[1,2-a]pyridin-3-yl)-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-(7-oxa-4-aza-
spiro[2.6]non-4-yl)-methanone
207
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxy-piperidin-1-yl)-methanone
208
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone
209
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(3-endo-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-
methanone
210
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-exo-ethyl-8-endo-hydroxy-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
211
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(5-endo-hydroxy-5-exo-methyl-2-aza-
bicyclo[2.2.1]hept-2-yl)-methanone
212
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-endo-hydroxy-8-exo-methyl-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
213
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-endo-hydroxy-8-exo-methyl-d3-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
214
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-exo-ethynyl-8-endo-hydroxy-3-aza-
bicyclo[3.2.1]oct-3-yl)-methanone
215
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(2-methoxymethyl-pyrrolidin-1-yl)-methanone
216
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(4-fluoro-piperidin-1-yl)-methanone
217
3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(6,6-difluoro-1,4-oxazepan-4-yl)-methanone
218
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(8-endo-hydroxy-3-aza-bicyclo[3.2.1]oct-3-yl)-
methanone
219
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxy-2,2-dimethyl-piperidin-1-yl)-
methanone
220
[3-Benzofuran-3-yl-1-(2,2-difluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(3-endo-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-
methanone
221
[3-Benzofuran-3-yl-1-(2-fluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-
6-yl]-(3-endo-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone
222
(3-Benzofuran-3-yl-1-propyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-(3-
endo-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone
223
tert-butyl N-[4-[3-(6,8-difluoroimidazo[1,2-a]pyridin-3-yl)-1-
(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carbonyl]-1,4-
oxazepan-6-yl]carbamate
224
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(6-hydroxy-1,4-oxazepan-4-yl)methanone
225
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(4,4-difluoro-1-piperidyl)methanone
226
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(3,3-difluoro-1-piperidyl)methanone
227
[3-Benzofuran-3-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-(3-hydroxy-piperidin-1-yl)-methanone
228
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(4-hydroxyazepan-1-yl)methanone
229
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(6,6-dideuterio-1,4-oxazepan-4-yl)methanone
230
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-[6-fluoro-1,4-oxazepan-4-yl]methanone
231
3-(benzofuran-3-yl)-N,N-di(cyclobutyl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carboxamide
232
3-(benzofuran-3-yl)-N,N-di(cyclopropyl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carboxamide
233
3-(benzofuran-3-yl)-N,N-diisopropyl-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carboxamide
234
3-(benzofuran-3-yl)-N-ethyl-N-isopropyl-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carboxamide
235
3-(benzofuran-3-yl)-N-cyclohexyl-N-ethyl-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridine-6-carboxamide
236
[3-(benzofuran-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(8-hydroxy-8-isopropyl-3-azabicyclo[3.2.1]octan-
3-yl)methanone
237
3-[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-3-yl]benzofuran-5-
carboxamide
238
(3,8-Diaza-bicyclo[3.2.1]oct-3-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
239
(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-[3-(6,8-difluoro-imidazo[l,2-
a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
240
(3-Amino-azepan-1-yl)-[3-(6,8-difluoro-imidazo[1,2-a]pyridin-3-
yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-
methanone
241
(6-Amino-1,4-oxazepan-4-yl)-[3-(6,8-difluoro-imidazo[1,2-
a]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
242
(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-(1H-indol-3-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone
243
[3-(1H-indol-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-
6-yl]-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone
244
3-[6-(Azepane-1-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-8-methyl-imidazo[1,2-a]pyridine-6-
carboxylic acid amide
245
3-[6-(Azepane-1-carbonyl)-1-propyl-1H-pyrazolo[4,3-c]pyridin-3-
yl]-imidazo[1,2-a]pyridine-6-carboxylic acid amide
246
3-[6-(1,4-Oxazepane-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-
pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-a]pyridine-6-carboxylic
acid amide
247
3-[6-(8-Oxa-3-aza-bicyclo[3.2.1]octane-3-carbonyl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-3-yl]-imidazo[1,2-
a]pyridine-6-carboxylic acid amide
248
Azepan-1-yl-[3-pyrazolo[1,5-a]pyrazin-3-yl-1-(2,2,2-trifluoro-
ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
249
1,4-Oxazepan-4-yl-[3-pyrazolo[1,5-a]pyrazin-3-yl-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
250
(1-Methanesulfonylmethyl-3-pyrazolo[1,5-a]pyrazin-3-yl-1H-
pyrazolo[4,3-c]pyridin-6-yl)-(1,4-oxazepan-4-yl)-methanone
251
[3-(benzimidazol-1-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
252
[3-(6-fluorobenzimidazol-1-yl)-1-(2,2,2-
trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-
yl)methanone
253
[3-furo[3,2-b]pyridin-3-yl-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-
c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone
254
[1,4]Oxazepan-4-yl-[3-(1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
255
[1,4]Oxazepan-4-yl-[3-(1H-pyrrolo[2,3-c]pyridin-3-yl)-1-(2,2,2-
trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone
256
(8-Oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-[3-(1H-pyrrolo[3,2-
c]pyridin-3-yl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-
c]pyridin-6-yl]-methanone
and pharmaceutically acceptable salts, solvates and prodrugs of any one of the afore-mentioned compounds.
12 . The compound of claim 1 for use as a medicament.
13 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
14 . The compound of claim 1 for use in therapy as a dual adenosine A 2A and A 2B receptor antagonist.
15 . The compound of claim 1 for use in the treatment or prevention of a hyperproliferative disease or disorder or an infectious disease or disorder.
16 . A method of treating or preventing a hyperproliferative disease or disorder the method comprising administering the compound of claim 1 to a subject in need thereof.
17 . A method of treating or preventing a hyperproliferative disease or disorder or an infectious disease or disorder, the method comprising administering the compound of claim 1 to a subject in need thereof.
18 . The method according to claim 16 , wherein said hyperproliferative disease or disorder is cancer.
19 . The method according to claim 18 , wherein the cancer is selected from the group consisting of acute granulocytic leukemia, acute lymphocytic leukemia, acute myeloid leukemia, adrenal cortex cancer, bladder cancer, brain cancer, breast cancer, cervical cancer, cervical hyperplasia, cervical cancer, chorio cancer, chronic granulocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, colon cancer, endometrial cancer, esophageal cancer, essential thrombocytosis, genitourinary carcinoma, glioma, glioblastoma, hairy cell leukemia, head and neck carcinoma, Hodgkin's disease, Kaposi's sarcoma, lung carcinoma, lymphoma, malignant carcinoid carcinoma, malignant hypercalcemia, malignant melanoma, malignant pancreatic insulinoma, medullary thyroid carcinoma, melanoma, multiple myeloma, mycosis fungoides, neuroblastoma, non-Hodgkin's lymphoma, non-small cell lung cancer, osteogenic sarcoma, ovarian carcinoma, pancreatic carcinoma, polycythemia vera, primary brain carcinoma, primary macroglobulinemia, prostatic cancer, renal cell cancer, rhabdomyosarcoma, skin cancer, small-cell lung cancer, soft-tissue sarcoma, squamous cell cancer, stomach cancer, testicular cancer, thyroid cancer and Wilms' tumor.
20 . The method according to claim 16 , wherein said hyperproliferative disease or disorder is selected from the group consisting of age-related macular degeneration, Crohn's disease, cirrhosis, a chronic inflammatory-related disorder, proliferative diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, granulomatosis, immune hyperproliferation associated with organ or tissue transplantation, and an immunoproliferative disease/disorder.
21 . The method according to claim 20 , wherein the hyperproliferative disease or disorder is an immunoproliferative disease or disorder, and wherein the immunoproliferative disease or disorder is selected from the group consisting of inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE), vascular hyperproliferation secondary to retinal hypoxia, and vasculitis.
22 . The method according to claim 17 , wherein the disease or disorder to be treated or prevented is an infectious disease or disorder, and wherein said infectious disease or disorder is selected from the group consisting of:
(a) virally induced infectious diseases which are caused by retroviruses, hepadnaviruses, herpesviruses, flaviviridae and/or adenoviruses, wherein the retroviruses are selected from lend viruses or oncoretroviruses, wherein the lentivirus is selected from the group consisting of HIV-1, HIV-2, FIV, BIV, SIVs, SHIV, CAEV, VMV and EIAV, wherein the oncoretrovirus is selected from the group consisting of HTLV-I, HTLV-II and BLV, wherein the hepadnavirus is selected from the group consisting of HBV, GSHV and WHV, wherein the herpesvirus is selected from the group consisting of HSV I, HSV II, EBV, VZV, HCMV and HHV 8, and wherein the flaviviridae are selected from the group consisting of HCV, West nile and Yellow Fever;
(b) bacterial infectious diseases which are caused by Gram-positive bacteria, wherein the Gram-positive bacteria are selected from the group consisting of methicillin-susceptible and methicillin-resistant staphylococci (including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus , and coagulase-negative staphylococci), glycopeptides-intermediate susceptible Staphylococcus aureus (GISA), penicillin-susceptible and penicillin-resistant streptococci (including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus avium, Streptococcus bovis, Streptococcus lactis, Streptococcus sanguis and Streptococci Group C (GCS), Streptococci Group G (GGS) and viridans streptococci), enterococci (including vancomycinsusceptible and vancomycin-resistant strains such as Enterococcus faecalis and Enterococcus faecium ), Clostridium difficile, Listeria monocytogenes, Corynebacterium jeikeium, Chlamydia spp (including C. pneumoniae ) and Mycobacterium tuberculosis;
(c) bacterial infectious diseases which are caused by Gram-negative bacteria, wherein the Gram-negative bacteria are selected from the group consisting of the genus Enterobacteriaceae, including Escherichia spp. (including Escherichia coli ), Klebsiella spp., Enterobacter spp., Citrobacter spp., Serratia spp., Proteus spp., Providencia spp., Salmonella spp., Shigella spp., the genus Pseudomonas (including P. aeruginosa ), Moraxella spp. (including M. catarrhalis ), Haemophilus spp. and Neisseria spp.; and
(d) infectious diseases induced by intracellular active parasites selected from the group consisting of the phylum Apicomplexa, Sarcomastigophora (including Trypanosoma, Plasmodia, Leishmania, Babesia or Theileria ), Cryptosporidia, Sacrocystida, Amoebia, Coccidia and Trichomonadia.
23 . The method according to claim 17 , wherein said compound is administered in combination with one or more further therapeutic agents.
24 . The method according to claim 17 , wherein the subject to be treated is a human.
25 . A set or kit comprising separate packs of:
(a) a compound as defined in claim 1 ; and
(b) a further therapeutic agent.
26 . In vitro use of a compound as defined in claim 1 as a dual adenosine A 2A and A 2B receptor antagonist.