Synthesis of 2-Methylsulfanyl-1H-imidazoles as Novel Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

✍ Scribed by Yasser M. Loksha; Mahmoud A. El-Badawi; Ahmed A. El-Barbary; Erik B. Pedersen; Claus Nielsen

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 158 KB
• Volume: 336
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200390017

✦ Synopsis

Abstract

α‐Aminoketone hydrochlorides 2a—d were synthesized by Dakin‐West reaction from L‐phenylalanine and L‐cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give 2‐methylsulfanyl‐1__H__‐imidazoles 4a—d with 4‐benzyl/4‐cyclohexylmethyl and 5‐ethyl/5‐isopropyl substituents. Coupling of 4a—d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N‐1 5a—d and N‐3 6a—h alkylated products. The synthesised compounds were tested for their activity against HIV‐1. The most active compounds have a cyclohexylmethyl group in the 5‐position of 6 and showed an activity against HIV‐1 comparable to the activity of Nevirapine.