Isoxazolines and isoxazoles as factor Xa inhibitors.
3,4,5-Trisubstituted isoxazolines (2) and isoxazoles (3) were prepared and evaluated for their in vitro and in vivo antithrombotic efficacy. They were compared to 3,5,5-trisubstituted isoxazolines (1) for Factor Xa selectivity and potency. They were also compared in an arterio-venous (A-V) shunt model of thrombosis.
Pruitt
J R
JR
The DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0500, USA. james.r.pruitt@dupontpharma.com
Pinto
D J
DJ
Estrella
M J
MJ
Bostrom
L L
LL
Knabb
R M
RM
Wong
P C
PC
Wright
M R
MR
Wexler
R R
RR
D000818:Animals; D018360:Crystallography, X-Ray; D065427:Factor Xa Inhibitors; D007555:Isoxazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008958:Models, Molecular; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000517:prevention & control
D065427:Factor Xa Inhibitors; D007555:Isoxazoles; D015842:Serine Proteinase Inhibitors