Evolution of anti-HIV drug candidates. Part 1: From α-Anilinophenylacetamide (α-APA) to imidoyl thiourea (ITU)

Stemming from work on a previous clinical candidate, loviride, and other α-APA derivatives, a new series of potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type and clinically important mutant strains of HIV-1. Synthetic work around a previous NNRTI clinical candidate (loviride) has led to diarylated imidoyl thioureas (ITUs) that are very active against both the wild-type and mutant strains of the HIV-1 virus.