Fibrinogen receptors

The hydantoin moiety has been utilized as a biostere for the peptide linkage, transforming a peptide lead into an orally available drug candidate. Therefore, an Arg-Gly-Asp-Ser tetrapeptide (18) lead structure was modified to a non-peptide RGD mimetic as an orally active fibrinogen receptor antagonist 19. ° ... 

Ku TW, Miller WH, Bondinell WE, Erhard KF, Keenan RM, Nichols AJ, Peishoff CE, Samanen JM, Wong AS, Huffman WF. Potent non-peptide fibrinogen receptor antagonists which present an alternative pharmacophore. J Med Chem 1995 38 9-12. 

A good example of this is the work completed on the fibrinogen receptor antagonist L-767,679 [10]. This compound exhibits extreme polarity due to its zwitter-... 

Constrained templates for fibrinogen receptor (GPIIb/IIIa) antagonists 2001BML2619... 

Fig. 3.11 Structures of the fibrinogen receptor antagonist L-767,679 and its benzyl ester (L-775,318) analogue.

An in vitro or ex vivo measure of drug effect, for example, mean inhibitory concentration (MIC) of an antimicrobial against bacterial culture inhibition of ADP-induced platelet aggregation with a fibrinogen receptor antagonist. 

Detection of thrombus is another clinically important goal. Contrast enhancement of vascular thrombosis has been achieved with a microbubble having a small peptide covalently attached to its surface that selectively binds to the GPIIb/llla fibrinogen receptor expressed on the surface of activated platelets that attach to thrombi. 

Hemler ME, Crouse C, Takada Y SonnenbergA. Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibrinogen receptor) and VLA-6 structures. J Biol Chem 1988 263(16) 7660-7665. 

BennetJS, Vilaire G. Exposure of platelet fibrinogen receptors by ADPand epinephrine. J Clin Invest 1979 64(5) 1393-1401. 

Benzylacetoacetate (5) was reduced to be n z y I - (.S ) - (+) - 3 - h y dm x y b u ty rale (6) by the yeast Candida schatavii MY 1831 (Scheme 19.7), which is considered a possible intermediate in the synthesis of L-734,217 (7), an experimental fibrinogen receptor antagonist.80 Initially, 8 microorganisms were tested for their reduction ability using 5 as substrate. The best culture, C. schatavii MY 1831, yielded product with an ee of 93% and an estimated conversion yield of >95% (by thin layer chromatography [TLC]). 

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