2-Acylimino-3H-thiazoline derivatives: a novel template for platelet GPIIb/IIIa receptor antagonists.
In the course of our research for the low-molecular weight RGD peptide mimics, we have found that a rigid 2-acylimino-3H-thiazoline structure is suitable for the peptide backbone mimics. Introduction of amidinophenyl and beta-alanine moiety as arginine and aspartic acid side-chain surrogates to this backbone mimic resulted in a highly potent fibrinogen receptor antagonist 2-(4-amidinobenzoylimino)-3,4-dimethyl-N-(2-carboxyethyl)-3H-thiazoline-5-carboxamide (7c), namely PS-028 (Ki = 46.5 +/- 5.8 microM).
Manaka
A
A
Taisho Pharmaceutical Co. Ltd., Medicinal Research Laboratories, Omiya-shi, Saitama, Japan.
Sato
M
M
Aoki
M
M
Tanaka
M
M
Ikeda
T
T
Toda
Y
Y
Yamane
Y
Y
Nakaike
S
S
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D020128:Inhibitory Concentration 50; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis; D010455:Peptides / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013844:Thiazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
C434803:2-acylimino-3H-thiazoline; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013844:Thiazoles; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen