Large-scale synthesis of GMP grade N'- [2-(2-thiophene) ethyl]-N'- [2- (5-bromopyridyl)] -thiourea (HI-443), a new anti-HIV drug candidate.
The thiourea compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (HI-443, CAS 258340-15-7), was found to be a potent anti-HIV agent with remarkable activity against nucleoside analog reverse transcriptase (NRT)-resistant, non-nucleoside analog reverse transcriptase (NNRT)-resistant, as well as multidrug-resistant HIV. Now the method of producing HI-443 under current Good Manufacturing Practice (cGMP) conditions on the scale of kilograms is reported. The availability of GMP-grade HI-443 will promote the preclinical and clinical development efforts aimed at making this new drug candidate available to HIV-infected persons.
DuMez
Darin
D
Paradigm Pharmaceuticals, 2139 Fourth Street, White Bear Lake, MN 55110, USA.
Venkatachalam
Taracad K
TK
Uckun
Fatih M
FM
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide; D004339:Drug Compounding / Q000592:standards; D004345:Drug Industry / Q000592:standards; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011725:Pyridines / Q000138:chemical synthesis*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D019380:Anti-HIV Agents; C403248:HI 443; D007202:Indicators and Reagents; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D013890:Thiourea; D004121:Dimethyl Sulfoxide