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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
Published on: January 1, 2016
Sulfonamidolactam inhibitors of coagulation factor Xa
Joanne M Smallheer1, Shuaige Wang, Mia L Laws
1Bristol-Myers Squibb Company, Cardiovascular Diseases Chemistry, PO Box 5400, Princeton, NJ 08543-5400, USA. joanne.smallheer@bms.com
Abstract:
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.
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