A commercially viable route and process to HIV PI GW640385X

ORGN 210

John Roberts, Synthetic Chemistry, Chemical Development, Synthetic Chemistry, Chemical Development, GlaxoSmithKline, Five Moore Drive, Research, Triangle Park, NC 27709-3398
The development of a commercially viable route and process to GW640385X, an HIV protease inhibitor currently in clinical trials, was recently developed at GlaxoSmithKline in Research Triangle Park. A compound with increased complexity from its marketed predecessors, e.g. Amprenavir, GW640385X was initially synthesized in 14 steps to satisfy early supply requirements. Both branches of this convergent approach were fraught with problems including unacceptable cost of goods limitations. The current in-house synthesis, recently used to produce over 150 kg of drug substance, consists of four stages.