Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists

Mikhail Krasavin; Alexei Lukin; Anna Bakholdina; Nikolay Zhurilo; Oleksandra Onopchenko; Petro Borysko; Sergey Zozulya; Daniel Moore; Irina G Tikhonova

doi:10.1016/j.ejmech.2017.09.019

Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists

Mikhail Krasavin, Alexei Lukin, Anna Bakholdina, Nikolay Zhurilo, Oleksandra Onopchenko, Petro Borysko, Sergey Zozulya, Daniel Moore, Irina G Tikhonova

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

An earlier reported series of 1,2,4-thiadiazole-based agonists of FFA1 (GPR40) was evolved into two structurally distinct series of compounds. One of the series (structurally related to known FFA1 agonist GW9508) displayed low micromolar potency while the other (representing a truncated version of the earlier reported potent FFA1 agonists) was, surprisingly, found to be devoid of agonist potency. In silico docking of representative compounds into the crystal structure of FFA1 revealed possible structural grounds for the observed SAR.

Original language	English
Pages (from-to)	229-238
Number of pages	10
Journal	European Journal of Medicinal Chemistry
Volume	140
Early online date	13 Sept 2017
DOIs	https://doi.org/10.1016/j.ejmech.2017.09.019
Publication status	Early online date - 13 Sept 2017

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Journal Article

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Krasavin, M., Lukin, A., Bakholdina, A., Zhurilo, N., Onopchenko, O., Borysko, P., Zozulya, S., Moore, D., & Tikhonova, I. G. (2017). Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists. European Journal of Medicinal Chemistry, 140, 229-238. Advance online publication. https://doi.org/10.1016/j.ejmech.2017.09.019

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AU - Krasavin, Mikhail

AU - Lukin, Alexei

AU - Bakholdina, Anna

AU - Zhurilo, Nikolay

AU - Onopchenko, Oleksandra

AU - Borysko, Petro

AU - Zozulya, Sergey

AU - Moore, Daniel

AU - Tikhonova, Irina G

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AB - An earlier reported series of 1,2,4-thiadiazole-based agonists of FFA1 (GPR40) was evolved into two structurally distinct series of compounds. One of the series (structurally related to known FFA1 agonist GW9508) displayed low micromolar potency while the other (representing a truncated version of the earlier reported potent FFA1 agonists) was, surprisingly, found to be devoid of agonist potency. In silico docking of representative compounds into the crystal structure of FFA1 revealed possible structural grounds for the observed SAR.

KW - Journal Article

U2 - 10.1016/j.ejmech.2017.09.019

DO - 10.1016/j.ejmech.2017.09.019

M3 - Article

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JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists

Abstract

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