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.
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 multidrug-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-I 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 agent.
Uckun
Fatih M
FM
Paradigm Pharmaceuticals, 2139 Fourth Street, White Bear Lake, MN 55110, USA. fatih_uckun@tmo.blackberry.net
Qazi
Sanjive
S
Venkatachalam
Taracad
T
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015195:Drug Design; D004351:Drug Resistance; D024921:Drug Resistance, Multiple, Viral; D005838:Genotype; D015658:HIV Infections / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011725:Pyridines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000737:chemistry; D010948:Viral Plaque Assay
D019380:Anti-HIV Agents; C403248:HI 443; D011725:Pyridines; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D014759:Viral Envelope Proteins; D054303:HIV Reverse Transcriptase; D013890:Thiourea