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US 9,868,727 B2Granted
Factor XIa inhibitors
AssigneeMerck Sharp & Dohme Corp.
InventorsWeiguo Liu, Scott D. Edmondson, Zhuyan Guo, Sung-Sau So, Anthony K. Ogawa, Rongze Kuang, Heping Wu, Amjad Ali, Ying-Duo Gao, Yu Jiang, Chunsing Li, Tingting Yu
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Abstract
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.
Claims16
A compound of the formula:
- wherein
- is a 5 or 6 membered heteroaryl ring, wherein said heteroaryl ring is optionally substituted with one to three substituents independently selected from the group consisting of nitro, cyano, oxo, Ra, (C═O)R4, (C═O)OR4, NR4R5, NH(C═O)R4, NH(C═O)OR4, SO2R4, SO2NR4R5, NR4SO2R5 and PO3R4;
- R1 is aryl, heteroaryl, C3-6 cycloalkyl or heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo, nitro, cyano, oxo, R4, OR4, (C═O)R4, (C═O)OR4, NR4R5, NH(C═O)R4, NH(C═O)OR4, C3-6 cycloalkyl and heteroaryl which is optionally substituted with R4;
- R2 is hydrogen or CH(R2a)(R2b);
- R2a is hydrogen, C1-6 alkyl, aryl, heteroaryl, C3-6 cycloalkyl, heterocyclyl or (C═O)NR4R5, wherein said alkyl group is optionally substituted with one to three substituents independently selected from the group consisting of halo, hydroxy and cyano, and wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo, nitro, cyano, oxo, R4 and OR4;
- R2b is hydrogen or C1-6 alkyl, which is optionally substituted with one to three substituents independently selected from the group consisting of halo, hydroxy and cyano;
- R3 is halo, cyano, (C═O)OR4 or R6;
- R4 is hydrogen or C1-6 alkyl, which is optionally substituted with one to three groups independently selected from the group consisting of halo and hydroxy;
- R5 is hydrogen or C1-6 alkyl, which is optionally substituted with one to three groups independently selected from the group consisting of halo and hydroxy;
- R6 is aryl, heteroaryl, C3-10 cycloalkyl or heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo, nitro, cyano, oxo, R4, OR4, (C═O)R4, (C═O)OR4, (C═O)NR4R5, NR4R5, NH(C═O)R4, NH(C═O)OR4, SO2R4, SO2NR4R5, NR4SO2R5 and PO3R4;
- Ra is hydrogen, halo, R4 or OR4;
- or a pharmaceutically acceptable salt thereof.
9 more elements
Dependencies are inferred from the claim text.