Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.
Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.
Becker
M R
MR
Department of Medicinal Chemistry, Rhône-Poulenc Rorer, Collegeville, PA 19426, USA.
Ewing
W R
WR
Davis
R S
RS
Pauls
H W
HW
Ly
C
C
Li
A
A
Mason
H J
HJ
Choi-Sledeski
Y M
YM
Spada
A P
AP
Chu
V
V
Brown
K D
KD
Colussi
D J
DJ
Leadley
R J
RJ
Bentley
R
R
Bostwick
J
J
Kasiewski
C
C
Morgan
S
S
D000818:Animals; D004285:Dogs; D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy
D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones