Noncovalent thrombin inhibitors incorporating an imidazolylethynyl P1.
A series of noncovalent tripeptidic thrombin inhibitors incorporating a unidazolylethynyl moiety at P1 was investigated. A number of compounds of this series were highly potent and selective versus trypsin, and several compounds demonstrated good oral absorption in rats (F = 58% for compound 19).
Lee
K
K
Life Science R&D, LG Chemical Ltd/Research Park, Science Town, Taejon, South Korea. kleec@lgchem.co.kr
Jung
W H
WH
Kang
M
M
Lee
S H
SH
D000114:Acetylene / Q000138:chemical synthesis / Q000494:pharmacology; D000480:Alkynes / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D006490:Hemostatics / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D000480:Alkynes; D006490:Hemostatics; D007093:Imidazoles; D015842:Serine Proteinase Inhibitors; D014357:Trypsin; D013917:Thrombin; D000114:Acetylene