This talk will discuss the medicinal chemistry story leading to the discovery of PF-06747775. The biologic target, TKI resistant EGFR, and our previous efforts in the area will be briefly discussed to provide context. Our program’s SAR discoveries and SBDD insights that led to PF-06747775 will be described. The impact of our design philosophy for irreversible inhibitors on this clinical candidate will be demonstrated through chemical biology experiments into off target reactivity. A major focus of the talk will be the development of the synthetic chemistry that supported these efforts. Several fit-for-purpose synthetic routes will be described that span from diversity-focused routes to more process friendly routes.

Discovery and early enablement of PF-06747775: A next generation irreversible inhibitor of mutant EGFR for the treatment of NSCLC

254th National Meeting (2017)

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