Sulfonamidolactam inhibitors of coagulation factor Xa.
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.
Smallheer
Joanne M
JM
Bristol-Myers Squibb Company, Cardiovascular Diseases Chemistry, PO Box 5400, Princeton, NJ 08543-5400, USA. joanne.smallheer@bms.com
Wang
Shuaige
S
Laws
Mia L
ML
Nakajima
Suanne
S
Hu
Zilun
Z
Han
Wei
W
Jacobson
Irina
I
Luettgen
Joseph M
JM
Rossi
Karen A
KA
Rendina
Alan R
AR
Knabb
Robert M
RM
Wexler
Ruth R
RR
Lam
Patrick Y S
PY
Quan
Mimi L
ML
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*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D007769:Lactams; D008024:Ligands; D010881:Piperidones; D013449:Sulfonamides