Alkylation of azoles: Synthesis of new heterocyclic-based AT1-non-peptide angiotensin (II) receptor antagonists

✍ Scribed by Amal Al-Azmi; Paulson George; Osman M. E. El-Dusouqui

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2007
• Tongue: English
• Weight: 363 KB
• Volume: 44
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570440302

✦ Synopsis

Abstract

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Several novel analogues of Losartan 2 were synthesized as potential non‐peptide angiotensin (II) receptor antagonists. In these non‐peptide analogues, the tetrazole and the substituted imidazole rings of Losartan 2 were replaced, respectively, by a carboxylic acid function or its methyl ester and substituted triazole, imidazole or benzimidazole moieties. The biphenyl bromide precursor 3 (BPE) used to introduce the linker between the acid/ester function and the heterocyclic moiety was synthesized using Suzuki biphenyl coupling and then incorporated into the target molecule by simple nucleophilic substitution. The fixed N‐aryl isomeric forms of several azole and benzimidazole tautomers were successfully separated by HPLC using 50% aqueous acetonitrile as eluent. Intermediate reaction products and final target compounds were fully characterized spectroscopically.