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Eur J Med Chem. 2017 Nov 10;140:229-238. doi: 10.1016/j.ejmech.2017.09.019. Epub 2017 Sep 13.

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

Author information

1
Saint Petersburg State University, Saint Petersburg 199034 Russia. Electronic address: m.krasavin@spbu.ru.
2
Lomonosov Institute of Fine Chemical Technologies, Moscow Technological University, Moscow 117571 Russia.
3
Enamine Ltd, Kyiv 02094, Ukraine.
4
Enamine Ltd, Kyiv 02094, Ukraine; Taras Shevchenko National University, 62 Volodymyrska, Kyiv 01033, Ukraine.
5
Molecular Therapeutics, School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Northern Ireland, UK.

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.

KEYWORDS:

1,2,4-Thiadiazole; Agonist potency; Free fatty acid receptor 1; GPR40; Heterocyclic bioisosteres; In silico docking

PMID:
28938138
DOI:
10.1016/j.ejmech.2017.09.019
[Indexed for MEDLINE]

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