Potent and selective bicyclic lactam inhibitors of thrombin: Part 3: P1' modifications.
The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors are described. We have explored the SAR around the P1' site. Modification of the P1' site has been found to affect potency and selectivity.
Plummer
J S
JS
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Berryman
K A
KA
Cai
C
C
Cody
W L
WL
DiMaio
J
J
Doherty
A M
AM
Eaton
S
S
Edmunds
J J
JJ
Holland
D R
DR
Lafleur
D
D
Levesque
S
S
Narasimhan
L S
LS
Rubin
J R
JR
Rapundalo
S T
ST
Siddiqui
M A
MA
Susser
A
A
St-Denis
Y
Y
Winocour
P
P
D000818:Animals; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007769:Lactams / Q000494:pharmacology*; D008956:Models, Chemical; D008958:Models, Molecular; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy
D006571:Heterocyclic Compounds; D007769:Lactams; D013917:Thrombin