Structure–activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure

A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenylnorstatine (Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) were designed and synthesized. From the structure–activity relationship of this series of compounds, SM-309515 was found to have potent antiviral activity against wild-type and resistant HIV-1s and to possess a desirable pharmacokinetic profile in dogs.

HIV protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure were designed and synthesized. These compounds exhibited excellent pharmacokinetic profile and potent antiviral activity against wild-type and resistant HIV-1s.Figure optionsDownload as PowerPoint slide