Regiospecific Synthesis of 5‐Halo‐substituted Thiophene Pyridyl Thiourea Compounds as Non‐nucleoside Inhibitors of HIV‐1 Reverse Transcriptase

Abstract

The regiospecific synthesis of 5‐halothiophenethylamines and halo‐substituted phenylethyl thioureas was accomplished with an overall yield of 45–60%. Condensation of t‐boc protected 2‐thiophenethylamine with N‐halo succinamide in dimethylformamide furnished the desired halo‐substituted thiophenethylamines. These thiophenethyl amines were further converted into biologically active thiourea compounds using thiocarbonyldiimidazole chemistry. Several of the halo‐substituted thiophene pyridyl thiourea compounds inhibited HIV‐1 reverse transcriptase (RT) at nanomolar concentrations.

Keywords:

• Thiourea compounds
• Non‐nucleoside inhibitors
• HIV‐1
• Reverse transcriptase