Compounds and compositions as TRK inhibitors

摘要

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TRK kinase activity.;wherein:
A is;X1 is CH or N;

主权项

1. A compound of Formula (I): wherein: A isX1 is CH or N;R1 is —C(O)NH2, —C(O)N(R7)2, —C(O)N(R8)2, —NR7C(O)R8, —NR7C(O)N(R7)2, —NR7C(O)N(R8)2, —NR7C(O)N(R9)2; —C(O)OR7, —NR7C(O)OR7, —NR7C(O)OR8, —C(O)NR7R8, —C(O)NR7C(O)OR7, —C(O)NR7C(O)NH2, —C(O)NR7C(O) N(R7)2 or H;each R2 is independently selected from H and C1-C6alkyl;each R3 is independently selected from H, C1-C6alkyl, —CN, —C(O)N(R7)2, —OR7 and halo, or the two R3 together with the C atom they are attached form a cyclopropyl group spiro attached to the pyrrolidine;or a R2 and a R3 together with the C atom they are attached form a cyclopropyl ring fused to the pyrrolidine;each R4 is independently selected from H, halo, —OR7, C1-C6alkyl, C1-C6alkyl substituted with 1-3 halo, C1-C6alkoxy substituted with 1-3 halo, —CN and —C(O)N(R7)2;each R5 is independently selected from H and C1-C6alkyl;each R6 is independently selected from H, C1-C6alkyl, —CN, —OR7 and halo;each R7 is independently selected from H, C1-C6alkyl or C1-C6alkyl substituted with 1-3 —OH;each R8 is independently selected from H, C1-C6alkyl, phenyl, benzyl, phenyl substituted with 1-3 groups independently selected from R6, benzyl substituted with 1-3 groups independently selected from R6, an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from O and N, a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from O and N which is substituted with 1-3 groups independently selected from R6, an unsubstituted C3-C6cycloalkyl, a C3-C6cycloalkyl substituted with 1-3 groups independently selected from R6, an unsubstituted 5-6 membered heteroaryl having 1 to 2 heteroatoms independently selected from O and N, a 5-6 membered heteroaryl having 1 to 2 heteroatoms independently selected from O and N which is substituted with 1-3 groups independently selected from R6;each R9 is a C1-C6alkyl and together with the N atom they are attached form an unsubstituted 5-6 membered heterocycloalkyl or a 5-6 membered heterocycloalkyl substituted with 1-3 groups independently selected from R6;m is 0, 1, 2, 3 or 4,n is 0, 1 or 2,or a pharmaceutically acceptable salt thereof.