Bryan Li
Pfizer Inc.-Groton, USA
Title: Exploratory process development of a second generation beta-amyloid cleaving enzyme inhibitor
Biography
Biography: Bryan Li
Abstract
Alzheimer’s disease (AD) is widely believed to be related to the production and deposition of the beta-amyloid (Aβ). Thus, beta-amyloid cleaving enzyme (BACE1) inhibitors, that can reduce the production of the Aβ peptide, are promising candidates for the treatment of AD. Pfizer researchers discovered a potent, selective BACE1 inhibitor that displayed good safety, tolerability, and pharmacokinetics from early stage clinical trials. The compound also exhibited excellent brain penetration, and potent in vivo efficacy. The exploratory active pharmaceutical ingredient (API) support strategy and the process development will be discussed. In this presentation, the synthesis of the complex target molecule will encompass the greening of a chiral isoxazoline production, continuous flow chemistry of a critical heteroaryl bromide-metal exchange and telescoped heteroaryl anion addition, and the GMP endgame development in multiple clinical campaigns.