Synthesis of 2-(aminocarbonylmethylthio)-1 H-imidazoles as novel Capravirine analogues

Abstract

Different analogues of Capravirine (AG-1549) or S-1153 were prepared by synthesis of 2-(5-benzyl-4-isopropyl-1-methyl-2,3-dihydro-1 H-imidazol-2-ylthio)acetamide ( 3a– c), ethyl [5-benzyl-1-(ethoxymethyl)-4-ethyl-1 H-imidazol-2-ylthio]acetate ( 10), 2-[5-alkyl-4-substituted 1-(pyridin-4-ylmethyl)-1 H-imidazol-2-ylthio]acetamides ( 12a– f), and 2-[5-benzyl-1-(benzyloxymethyl)-4-isopropyl-1 H-imidazol-2-ylthio]acetamides ( 14a– l) from their corresponding amino acids through a sequence of reactions: Dakin–West reaction, hydrolysis, condensation with thiocyanate derivatives, alkylation with 2-iodoacetamide and ethyl chloroacetate, and coupling with 4-pyridylmethyl chloride, ethoxymethyl chloride and benzyloxymethyl chloride. All the synthesized compounds were screened for their activity against HIV-1 (wild type) and some of them (especially Capravirine like structures) were found active.