Novel bicyclic lactam inhibitors of thrombin: highly potent and selective inhibitors.
The potency and selectivity of a previous series of low molecular weight thrombin inhibitors were improved through modifications of the P1 and P3 residues. Introduction of diphenyl substituted sulfonamides in the P3 moiety led to highly efficacious compounds. By correctly selecting the combination of P1 and P3 residues, high levels of potency, selectivity and in vivo efficacy were obtained.
St-Denis
Yves
Y
Shire BioChem., 275 Armand-Frappier Blvd., Laval, H7V 4A7, Québec, Canada.
Lévesque
Sophie
S
Bachand
Benoit
B
Edmunds
Jeremy J
JJ
Leblond
Lorraine
L
Préville
Patrice
P
Tarazi
Micheline
M
Winocour
Peter D
PD
Siddiqui
M Arshad
MA
D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*
D000991:Antithrombins; D007769:Lactams