Rational Development of Cyclopropane-Based Target-Selective Compounds such as GABA Transporter Inhibitors – University of Copenhagen

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DRA > Activities > 2017 > Symposia and lectures > Rational Development o...

Rational Development of Cyclopropane-Based Target-Selective Compounds such as GABA Transporter Inhibitors

Lecture by Professor Satoshi Shuto, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan

Abstract
In drug developments, when the target protein structure is unknown, an alternative approach other than the structure-based designing (SBDD) is needed. Using the characteristic steric and stereoelectronic features of cyclopropane, we present the three-dimensional (3D) structural diversity-oriented strategy, which is not structure-based but ligand and organic chemistry-based approach to the rational drug development. In this strategy, a conformationally flexible bioactive compound (i.e., GABA) can be a prototype ligand, and it is converted into a series of cyclopropane-based conformationally restricted analogues consisting of stereo- and/or regio-isomers with 3D structural diversity. Because of the 3D structural diversity, the restricted one of these isomers can be identical or analogous to the bioactive form of the prototype resulting in finding a lead that is superior to the prototype ligand in its target selectivity and/or binding potency. By this strategy, we have developed various target-selective compounds such as a BGT1 inhibitor.

The lecture is organized on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy by Petrine Wellendorph and Bente Frølund, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.

Participation is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.