Design, synthesis and biological evaluation of non-peptide PAR1 thrombin receptor antagonists based on small bifunctional templates: arginine and phenylalanine side chain groups are keys for receptor activity.

Abstract:

:In the present study, we report the synthesis and biological evaluation of a series of new non-peptide PAR(1) mimetic receptor antagonists, based on conformational analysis of the S(42)FLLR(46) tethered ligand (TL) sequence of PAR(1). These compounds incorporate the key pharmacophore groups in the TL sequence, guanidyl, amino and phenyl, which are essential for triggering receptor activity. Compounds 5 and 15 (50-100 microM) inhibited both TFLLR-amide (10 microM) and thrombin-mediated (0.5 and 1 U/ml; 5 and 10 microM) calcium signaling in a cultured human HEK cell assay.

journal_name

Amino Acids

journal_title

Amino acids

authors

Androutsou ME,Saifeddine M,Hollenberg MD,Matsoukas J,Agelis G

doi

10.1007/s00726-009-0306-z

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

985-90

issue

4

eissn

0939-4451

issn

1438-2199

journal_volume

38

pub_type

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