Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide

Authors
Zhang, HC McComsey, DF White, KB Addo, MF Andrade-Gordon, P Derian, CK Oksenberg, D Maryanoff, BE
Citation
Hc. Zhang et al., Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide, BIOORG MED, 11(16), 2001, pp. 2105-2109
Citations number
35
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
16
Year of publication
2001
Pages
2105 - 2109
Database
ISI
SICI code
0960-894X(20010820)11:16<2105:TR(ASS>2.0.ZU;2-5
Abstract
A novel, 10-step, solid-phase method, based on a secondary amide linker, wa s developed to construct a diverse library of indole-based SFLLR peptide mi metics as thrombin receptor (protease-activated receptor 1, PAR-I) antagoni sts. The key steps include stepwise reductive alkylation, urea formation, a nd Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity. (C) 2001 Elsevi er Science Ltd. All rights reserved.