Novel thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine mimetics: optimization via modification of P1 and P3 moieties.
Optimization of lead compounds 1 and 2 resulted in novel, selective, and potent thrombin inhibitors incorporating weakly basic heterobicyclic P(1)-arginine mimetics. The design, synthesis, and biological activity of racemic thrombin inhibitors 17-29 and enantiomerically pure thrombin inhibitors 30-33 are described. The arginine side-chain mimetics used in this study are 4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine, 4,5,6,7-tetrahydro-2H-indazole, and 2-imino-4,5,6,7-tetrahydro-1,3-benzothiazol-3(2H)-ylamine.
Kranjc
Andreja
A
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Peterlin-Masic
Lucija
L
Ilas
Janez
J
Prezelj
Andrej
A
Stegnar
Mojca
M
Kikelj
Danijel
D
D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005343:Fibrinolytic Agents; D015842:Serine Proteinase Inhibitors; D001120:Arginine; D013917:Thrombin