title: Sulfonamidolactam inhibitors of coagulation factor Xa.
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.
authors.affiliation: Bristol-Myers Squibb Company, Cardiovascular Diseases Chemistry, PO Box 5400, Princeton, NJ 08543-5400, USA. joanne.smallheer@bms.com
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Smallheer
authors.forename: Shuaige
authors.initials: S
authors.lastname: Wang
authors.forename: Mia L
authors.initials: ML
authors.lastname: Laws
authors.forename: Suanne
authors.initials: S
authors.lastname: Nakajima
authors.forename: Zilun
authors.initials: Z
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Irina
authors.initials: I
authors.lastname: Jacobson
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.forename: Alan R
authors.initials: AR
authors.lastname: Rendina
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
authors.forename: Mimi L
authors.initials: ML
authors.lastname: Quan
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001780:Blood Coagulation Tests; D065427:Factor Xa Inhibitors; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D008956:Models, Chemical; D010881:Piperidones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D007769:Lactams; D008024:Ligands; D010881:Piperidones; D013449:Sulfonamides