Computer-Aided Selective Optimization of Side Activities of Talinolol.
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ABSTRACT:
SUBMITTER: Hiesinger K
PROVIDER: S-EPMC6580380 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Computer-Aided Selective Optimization of Side Activities of Talinolol.
Hiesinger Kerstin K Kramer Jan S JS Achenbach Janosch J Moser Daniel D Weber Julia J Wittmann Sandra K SK Morisseau Christophe C Angioni Carlo C Geisslinger Gerd G Kahnt Astrid S AS Kaiser Astrid A Proschak Anna A Steinhilber Dieter D Pogoryelov Denys D Wagner Karen K Hammock Bruce D BD Proschak Ewgenij E
ACS medicinal chemistry letters 20190529 6
Selective optimization of side activities is a valuable source of novel lead structures in drug discovery. In this study, a computer-aided approach was used to deorphanize the pleiotropic cholesterol-lowering effects of the beta-blocker talinolol, which result from the inhibition of the enzyme soluble epoxide hydrolase (sEH). X-ray structure analysis of the sEH in complex with talinolol enables a straightforward optimization of inhibitory potency. The resulting lead structure exhibited <i>in viv ...[more]
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