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Medicinal-Pharmaceutical Chemistry Commons

Open Access. Powered by Scholars. Published by Universities.®

2016

University of Nebraska - Lincoln

David Berkowitz Publications

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

“Zipped Synthesis” By Cross-Metathesis Provides A Cystathionine Β‑Synthase Inhibitor That Attenuates Cellular H2S Levels And Reduces Neuronal Infarction In A Rat Ischemic Stroke Model, Christopher D. Mccune, Su Jing Chan, Matthew L. Beio, Weijun Shen, Woo Jin Chung, Laura M. Szczesniak, Chou Chai, Shu Qing Koh, Peter T.-H. Wong, David B. Berkowitz Mar 2016

“Zipped Synthesis” By Cross-Metathesis Provides A Cystathionine Β‑Synthase Inhibitor That Attenuates Cellular H2S Levels And Reduces Neuronal Infarction In A Rat Ischemic Stroke Model, Christopher D. Mccune, Su Jing Chan, Matthew L. Beio, Weijun Shen, Woo Jin Chung, Laura M. Szczesniak, Chou Chai, Shu Qing Koh, Peter T.-H. Wong, David B. Berkowitz

David Berkowitz Publications

The gaseous neuromodulator H2S is associated with neuronal cell death pursuant to cerebral ischemia. As cystathionine β-synthase (CBS) is the primary mediator of H2S biogenesis in the brain, it has emerged as a potential target for the treatment of stroke. Herein, a “zipped” approach by alkene cross-metathesis into CBS inhibitor candidate synthesis is demonstrated. The inhibitors are modeled after the pseudo-C2-symmetric CBS product (L,L)-cystathionine. The “zipped” concept means only half of the inhibitor needs be constructed; the two halves are then fused by olefin cross-metathesis. Inhibitor design is also mechanism-based, exploiting the favorable kinetics ...