N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (HI-443), a Rationally Designed Non-Nucleoside Reverse Transcriptase Inhibitor Compound with Potent Anti-HIV Activity

Abstract The in vitro activity profile of N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (CAS 258340-15-7, HI-443) was examined against 38 clinical isolates of HIV-1. HI-443 inhibited the replication and/or infectivity of each of the 7 HIV-1 isolates of non-B envelope subtype, each of the 22 isolates with genotypic nucleoside reverse transcriptase inhibitor (NRTI) resistance, each of the 6 multi-drug-resistant HIV isolates with genotypic NRTI/non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, each of the 3 isolates with no RT mutations, and each of the 3 laboratory strains of HIV-1 with NNRTI or NNRTI/NRTI resistance. The potency of HI-443 against clinical HIV-1 isolates with NRTI- or NNRTI-resistance warrants the further development of this rationally designed NNRTI as a new anti-HIV agents.

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