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Synthesis of 2‐Methylsulfanyl‐1 H ‐imidazoles as Novel Non‐nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Author(s) -
Loksha Yasser M.,
ElBadawi Mahmoud A.,
ElBarbary Ahmed A.,
Pedersen Erik B.,
Nielsen Claus
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200390017
Subject(s) - chemistry , potassium thiocyanate , isopropyl , alkylation , thioether , imidazole , stereochemistry , medicinal chemistry , organic chemistry , catalysis
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.