FACTOR XIa INHIBITORS

摘要

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.;

主权项

1. A compound of the formula: whereinis heteroaryl, which is optionally substituted with one to three groups independently selected from the group consisting of halo, methyl and cyano;
X is N or CR1b; Z is CH2, C═O or CH(C═O)OH; R1a is NH2 or (C1-3 alkyl)NH2; R1b is hydrogen, C1-3 alkyl, F or Cl; R1c is hydrogen, C1-3 alkyl, F or Cl; R1d is hydrogen, C1-3 alkyl, F or Cl; or R1a and R1b can be taken together with the atoms between them to form a 4 to 7 membered heterocyclyl ring; each R2 is independently selected from the group consisting of halo, cyano, hydroxy, OR3, C1-6 alkyl, C(O)OH, C(O)OR3, (R3)C(O)OH, (R3)C(O)OR4, NR5R6, (R3)NR5R6, NHCOR3, NHC(O)OR3, NHC(O)OC3-6 cycloalkyl, NHC(O)O(R3)OR4, NHC(O)O(R3)C(O)OH, (R3)NHC(O)OR4, NHCONR5R6, NHSO2R3, CONR5R6, CH2CONR5R6 and NHCONH(R3)heterocyclyl; R3 is hydrogen or C1-6 alkyl, wherein said alkyl is optionally substituted with one to three halo or hydroxy; R4 is hydrogen or C1-6 alkyl, wherein said alkyl is optionally substituted with one to three halo; R5 is hydrogen or C1-6 alkyl; R6 is hydrogen or C1-6 alkyl; R7 is hydrogen, C1-6 alkyl, CO2R3, COR3 or CONR5R6, wherein said alkyl is optionally substituted with one to three halo; y is an integer between one and four; z is an integer between zero and three; or a pharmaceutically acceptable salt thereof.