The Challenge of CNS Drug Discovery: 5-HT1B Ligands as Potential Agents for the Treatment of Anxiety and Depression
Peter Bernstein,
Sr. Principal Scientist
AstraZeneca US Research
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Abstract: The serotonin 5-hydroxytryptamine 1B receptor (5-HT1B) has been found to play a crucial role in the modulation of synaptic release of serotonin. Since clinically effective antidepressants enhance serotonergic neurotransmission it has been hypothesized that 5-HT1B antagonists are potential agents for the treatment of anxiety and depression.
AstraZeneca's research in this area will be described, with a focus on our providing compounds that will effectively test this hypothesis by: the discovery of multiple clinical candidates, the development of the first 5-HT1B PET ligand, and the synergies achieved in CNS drug discovery by the combination of these work streams.
Presenter Biography: BS, University of Rochester 1973, in Chemistry with High Distinction
PhD, Columbia University, 1977, in Organic Chemistry
Fellow, Department Of Chemistry, University of Wisconsin, Madison, 1979
In 1979, after doctoral studies with Professor Gilbert Stork, Columbia University, and a postdoctoral fellowship with Professor Barry Trost, University of Wisconsin, Madison, WI, Peter joined the Medicinal Chemistry Department of ICI Pharmaceuticals Group in Wilmington, DE. Peter has stayed with that group, working through its spin-off as Zeneca Pharmaceuticals and then through its merger with Astra Pharmaceuticals to form AstraZeneca Pharmaceuticals.
Peter has worked on many targets and has put >10 compounds into clinical development. Early in his career he started, and worked on, ICI’s leukotriene antagonist project and helped discover and develop Accolate™, the first LTRA to be approved in the US. After developing a potential back-up, ZD3523, he moved on to developing inhibitors of human neutrophil elastase. Two compounds from those efforts, ZD8321 and ZD0892 entered clinical development. Since then he has worked on, or led, projects targeting: neurokinin antagonists, β-estrogen agonists, γ-secretase inhibitors, H3 antagonists, and 5HT1b antagonists. In the area of neurokinin antagonists he led the chemistry teams working on dual NK1/NK2 antagonists for pulmonary disease [e.g. ZD6021 and ZD2249] and NK1 antagonists [e.g. ZD4974] targeted for CNS indications. Recently, he led the chemistry of, and then was project leader for, the 5HT1b-antagonist program and he also led the H3 antagonist program.
Peter is an author on over 170 scientific papers, presentations, and patents. He is active in the broader scientific community as: speaker, conference organizer, and board member. Currently, he serves as Industrial Councilor for the MEDI Division of the ACS, is on the Scientific Advisory Board for the Keystone Symposia, and sits on the editorial board of Topics in Medicinal Chemistry. He was the Chair of the 2004 Gordon Research Conference on Medicinal Chemistry and spent 8 years as Member and Chair of the Carothers Award Committee of the Delaware Section ACS. At AstraZeneca, in addition to managerial duties as a Project Chemistry Leader, he has progressed on the Scientific Ladder and is a Senior Principal Scientist.
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