Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold

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Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold. / Krasavin, Mikhail; Lukin, Alexey; Zhurilo, Nikolay; Kovalenko, Alexey; Zahanich, Ihor; Zozulya, Sergey.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 31, No. 6, 01.11.2016, p. 1404-1410.

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

Author

Krasavin, Mikhail ; Lukin, Alexey ; Zhurilo, Nikolay ; Kovalenko, Alexey ; Zahanich, Ihor ; Zozulya, Sergey. / Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2016 ; Vol. 31, No. 6. pp. 1404-1410.

BibTeX

@article{668d34142e76414d83ab309280a5bd3b,

title = "Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold",

abstract = "1,3,4-Thiadiazole was explored as a more polar, heterocyclic replacement for the phenyl ring in the 3-arylpropionic acid pharmacophore present in the majority of GPR40 agonists. Out of 13 compounds synthesized using a flexible, three-step protocol (involving no chromatographic purification), four compounds were confirmed to activate the target in micromolar concentration range. While the potency of the series should be subject of further optimization, the remarkable aqueous solubility and microsomal stability observed for the lead compound (8g) apparently attests to this new scaffold{\textquoteright}s high promise in the GPR40 agonist field.",

keywords = "Agonists, aqueous solubility, bioisosteric replacement, cLogP, free fatty acid receptor 1, GPR40, metabolic stability, total polar surface area",

author = "Mikhail Krasavin and Alexey Lukin and Nikolay Zhurilo and Alexey Kovalenko and Ihor Zahanich and Sergey Zozulya",

year = "2016",

month = nov,

day = "1",

doi = "10.3109/14756366.2016.1142984",

language = "English",

volume = "31",

pages = "1404--1410",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

issn = "1475-6366",

publisher = "Taylor & Francis",

number = "6",

}

RIS

TY - JOUR

T1 - Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold

AU - Krasavin, Mikhail

AU - Lukin, Alexey

AU - Zhurilo, Nikolay

AU - Kovalenko, Alexey

AU - Zahanich, Ihor

AU - Zozulya, Sergey

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 1,3,4-Thiadiazole was explored as a more polar, heterocyclic replacement for the phenyl ring in the 3-arylpropionic acid pharmacophore present in the majority of GPR40 agonists. Out of 13 compounds synthesized using a flexible, three-step protocol (involving no chromatographic purification), four compounds were confirmed to activate the target in micromolar concentration range. While the potency of the series should be subject of further optimization, the remarkable aqueous solubility and microsomal stability observed for the lead compound (8g) apparently attests to this new scaffold’s high promise in the GPR40 agonist field.

AB - 1,3,4-Thiadiazole was explored as a more polar, heterocyclic replacement for the phenyl ring in the 3-arylpropionic acid pharmacophore present in the majority of GPR40 agonists. Out of 13 compounds synthesized using a flexible, three-step protocol (involving no chromatographic purification), four compounds were confirmed to activate the target in micromolar concentration range. While the potency of the series should be subject of further optimization, the remarkable aqueous solubility and microsomal stability observed for the lead compound (8g) apparently attests to this new scaffold’s high promise in the GPR40 agonist field.

KW - Agonists

KW - aqueous solubility

KW - bioisosteric replacement

KW - cLogP

KW - free fatty acid receptor 1

KW - GPR40

KW - metabolic stability

KW - total polar surface area

UR - http://www.scopus.com/inward/record.url?scp=84959057647&partnerID=8YFLogxK

U2 - 10.3109/14756366.2016.1142984

DO - 10.3109/14756366.2016.1142984

M3 - Article

C2 - 26899762

AN - SCOPUS:84959057647

VL - 31

SP - 1404

EP - 1410

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 6

ER -

ID: 9432352