Selective 3-amino-2-pyridinone acetamide thrombin inhibitors incorporating weakly basic partially saturated heterobicyclic P1-arginine mimetics.
Novel, highly selective and potent thrombin inhibitors were identified as a result of combing the 3-benzylsulfonylamino-2-pyridinone acetamide P(2)-P(3) surrogate with weakly basic partially saturated heterobicyclic P(1)-arginine mimetics 1-8. The design, synthesis, biological activity, and the binding modes of non-covalent thrombin inhibitors featuring P(1)-4,5,6,7-tetrahydroindazole, 5,6,7,8-tetrahydroquinazoline, and 4,5,6,7-tetrahydrobenzothiazole moieties are described.
Peterlin-Masic
Lucija
L
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Kranjc
Andreja
A
Marinko
Petra
P
Mlinsek
Gregor
G
Solmajer
Tomaz
T
Stegnar
Mojca
M
Kikelj
Danijel
D
D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D010881:Piperidones / Q000737:chemistry* / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry
C016997:3-aminopiperidine-2-one; D000081:Acetamides; D000991:Antithrombins; D010881:Piperidones; D011728:Pyridones; D001120:Arginine; D013917:Thrombin