135321-13-0Relevant articles and documents
Low molecular weight, non-peptide fibrinogen receptor antagonists
Alig,Edenhofer,Hadvary,Hurzeler,Knopp,Muller,Steiner,Trzeciak,Weller
, p. 4393 - 4407 (2007/10/02)
The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin α(IIb)β3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N- terminal arginine by p-amidinophenylalanine or the Gly moiety by m- aminobenzoic acid led to compounds which are superior to the lead peptide with regard to activity and selectivity for GP IIb-IIIa vs the closely related vitronectin receptor α(v)β3. By random screening [(p- amidinobenzenesulfonamido)ethyl]-p-phenoxyacetic acid derivatives have been identified as fibrinogen receptor antagonists. Further structure-activity relationship studies culminated in the preparation of N-[N-[N-(p- amidinobenzoyl)-β-alanyl]-L-α-aspartyl]-3-phenyl-L-alanine (29h, Ro 43- 5054) and [[1-[N-(p-amidinobenzoyl)-L-tyrosyl]-4-piperidinyl]oxy]acetic acid (37f, Ro 44-9883), which exhibit very high activity as platelet aggregation inhibitors (IC50s 0.06 and 0.03 μM, respectively, human PRP/ADP) as well as marked selectivity for GP IIb-IIIa vs α(v)β3. Since the activity of 37f in dogs declines according to a two-compartment model with an initial phase having a t( 1/2 ) of 8 min and a second phase with a t( 1/2 ) of 110 min, this compound is a suitable candidate for the development as iv platelet inhibitor.
Novel benzoic and phenylacetic acid derivatives
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, (2008/06/13)
The compound of the formula STR1 wherein R1, R2 and R3 have the significance given in the description, can be used as medicaments for the therapy and prophylaxis of disorders such as thromboses, stroke, cardiac infarct, inflammations and arteriosclerosis as well as for the treatment of tumours.
