Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications.
Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.
St-Denis
Y
Y
BioChem Therapeutic Inc., Laval, Québec, Canada.
Augelli-Szafran
C E
CE
Bachand
B
B
Berryman
K A
KA
DiMaio
J
J
Doherty
A M
AM
Edmunds
J J
JJ
Leblond
L
L
Lévesque
S
S
Narasimhan
L S
LS
Penvose-Yi
J R
JR
Rubin
J R
JR
Tarazi
M
M
Winocour
P D
PD
Siddiqui
M A
MA
D000818:Animals; D018360:Crystallography, X-Ray; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D005343:Fibrinolytic Agents; D007769:Lactams; D015842:Serine Proteinase Inhibitors; D013917:Thrombin