Bristol-Myers Squibb Lecture

Wednesday, November 7th
Dr. William Rick Ewing
“Part 1. Metabolism Driven Pharmacokinetic Optimization of Dual Inhibitors of Angiotensin 1 and Endothelin A Receptors: Part 2. Synthesis of triazolopyridines and triazolopyrimidines using a modified Mitsunobu reaction ”

4:15pm - 5:15pm
Braun Lecture Hall
S.G.Mudd Chemistry Building
Stanford University


This is the first of two special lectures hosted by the Bristrol-Myers Squibb Company in support of synthetic organic chemistry. The second lecture will be given by Professor Kevan Shokat from the University of California at San Franicsco and will start at 5:30.

These lectures are free and open to the public. All Stanford University Chemistry students are encouraged to attend this special event.

About the lecture:
Part 1. Dual antagonists of angiotensin II and endothelin receptors have potential therapeutic application as anti-hypertensive agents. During investigations of chemotypes with dual inhibitory properties, interactions with cytochrome P450 3A4 were found to lead to highly variable pharmacokinetics. Sites of hydroxylation were identified through in-vitro CYP3A4 metabolism studies. Structure activity relationship efforts focused on reducing metabolic rates, resulting in BMS-509701, a potent dual antagonist in-vitro, which had optimized pharmacokinetic and pharmacodynamic properties.

Part 2. Bicyclic heterocyles represent a motif of interest for the medicinal chemist in the strategic replacement of peptide bonds. During the course of an SAR program, a novel synthesis of triazolopyridines was discovered. The synthesis of triazolopyridines under mild conditions using a modified Mitsunobu reaction starting from acylated 2-hydrazinopyridines and acylated-hydrazinopyrimidines will be described.

About Ewing:
Rick Ewing is a research director in medicinal chemistry at Bristol Myers Squibb. His research is focused on the discovery of therapeutic agents for the treatment of diabetes and obesity. Rick received his PhD degree from the University of Pennsylvania with Professor Madeleine Joullie where his research focused on the synthesis of cyclic depsipeptides, methodology for the synthesis of peptide mimetics and functionalized pyrrolidines, and the design of angiogenesis inhibitors (in collaboration with Judah Folkman). Rick’s current research interests are, methodology development for the synthesis of novel heterocycles, peptide mimetics, structure based drug design, and structural elicitation of screening deck impurities.

Questions
Please contact Patricia Dwyer at 650-723-4770.