Development of commercially viable enantioselective processes for HIV-1 NNRTIs

Area of Science:

• Medicinal Chemistry
• Process Chemistry
• Pharmaceutical Development

Background:

• Quinazolinone derivatives have shown promise as HIV-1 drug candidates.
• DPC-961 and DPC-963 are specific quinazolinone-based compounds investigated for HIV-1 treatment.
• Accelerated development programs present unique challenges in drug substance production.

Purpose of the Study:

• To review the process research and development (R&D) of DPC-961 and DPC-963.
• To detail the synthetic evolution of these quinazolinone-based HIV-1 drug candidates.
• To highlight challenges encountered during the scale-up and commercialization of these drug substances.

Main Methods:

• Chronological review of synthetic process evolution.
• Analysis of process development from laboratory to kilogram scale.
• Examination of challenges in accelerated drug development.

Main Results:

• Successful transition from racemic syntheses to efficient routes for kilogram-scale production.
• Development of commercially viable manufacturing processes for DPC-961 and DPC-963.
• Identification and resolution of key challenges during accelerated process development.

Conclusions:

• The R&D journey of DPC-961 and DPC-963 demonstrates successful process optimization for HIV-1 drug candidates.
• Scalable and commercially viable synthetic routes were established despite accelerated timelines.
• The review provides insights into overcoming process development hurdles in pharmaceutical manufacturing.