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.