Synthesis and activity studies of conformationally restricted alpha-ketoamide factor Xa inhibitors.
Conformationally restricted borolysine compounds containing a 2-(2-cyanophenylthio) benzoyl in the P3 position unexpectedly led to enhanced factor Xa inhibition. In an effort to improve both the potency and selectivity of this series by extending into the S' domain, we have replaced the boronic acid with alpha-ketoamides, utilizing a novel process that was developed in our labs.
Cacciola
J
J
DuPont Pharmaceuticals Company, Wilmington, DE 19880-0500, USA. joseph.cacciola@dupontpharma.com
Fevig
J M
JM
Stouten
P F
PF
Alexander
R S
RS
Knabb
R M
RM
Wexler
R R
RR
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D008958:Models, Molecular; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors