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JMC_15_12_2020.pdf (7.3 MB)

Structural Determinants for the Mode of Action of the Imidazopyridine DS2 at d-containing g-Aminobutyric Acid Type A (GABAA) Receptors

preprint
submitted on 17.12.2020, 07:48 and posted on 23.12.2020, 07:44 by Bente Frølund, Frederik Rostrup, Christina Birkedahl Falk-Petersen, Kasper Harpsøe, Stine Buchleithner, Irene Conforti, Sascha Jung, David E. Gloriam, Tanja Schirmeister, Petrine Wellendorph
A SAR study of the delta-selective positive modulators DS2 was performed to assist the quest for the binding site. The modulatory effect was measured using a fluorometric inaging plate reader (FLIPR) membrane potential (FMP) functional assay. Specific positions in the structural scaffold of DS2 was found to severly affect the pharmacological profile.
Analogs superior to DS2 were identified displaying higher potency and selectivity for the alfa4beta1delta over alfa4beta1gamma.

History

Email Address of Submitting Author

bfr@sund.ku.dk

Institution

University of Copenhagen, Department of Drug Design and Pharmacology

Country

Denmark

ORCID For Submitting Author

0000-0001-5476-6288

Declaration of Conflict of Interest

no conflict of interest

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