Sulfonamidolactam inhibitors of coagulation factor Xa
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- 作者：Joanne M. Smallheer ; Shuaige Wang ; Mia L. Laws ; Suanne Nakajima ; Zilun Hu ; Wei Han ; Irina Jacobson ; Joseph M. Luettgen ; Karen A. Rossi ; Alan R. Rendina ; Robert M. Knabb ; Ruth R. Wexler ; Patrick Y.S. L
- 关键词：Factor Xa inhibitors ; Anticoagulant ; Serine protease inhibitors ; Antithrombotic
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：1 April 2008
- 年：2008
- 卷：18
- 期：7
- 页码：2428-2433
- 全文大小：272 K
文摘
As part of an effort to identify novel backups for previously reported pyrazole-based coagulation Factor Xa inhibitors, the pyrazole 5-carboxamide moiety was replaced by 3-(sulfonylamino)-2-piperidone. This led to the identification of a structurally diverse chemotype that was further optimized to incorporate neutral or weakly basic aryl and heteroaryl P1 groups while maintaining good potency versus Factor Xa. Substitution at the sulfonamide nitrogen provided further improvements in potency and as did introduction of alternate P4 moieties.