Standard

Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835. / Krasavin, Mikhail; Lukin, Alexey; Bagnyukova, Daria; Zhurilo, Nikolay; Golovanov, Aleksei; Zozulya, Sergey; Zahanich, Ihor; Moore, Daniel; Tikhonova, Irina G.

в: European Journal of Medicinal Chemistry, Том 127, 01.01.2017, стр. 357-368.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

Harvard

Krasavin, M, Lukin, A, Bagnyukova, D, Zhurilo, N, Golovanov, A, Zozulya, S, Zahanich, I, Moore, D & Tikhonova, IG 2017, 'Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835', European Journal of Medicinal Chemistry, Том. 127, стр. 357-368. https://doi.org/10.1016/j.ejmech.2017.01.005

APA

Krasavin, M., Lukin, A., Bagnyukova, D., Zhurilo, N., Golovanov, A., Zozulya, S., Zahanich, I., Moore, D., & Tikhonova, I. G. (2017). Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835. European Journal of Medicinal Chemistry, 127, 357-368. https://doi.org/10.1016/j.ejmech.2017.01.005

Vancouver

Krasavin M, Lukin A, Bagnyukova D, Zhurilo N, Golovanov A, Zozulya S и пр. Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835. European Journal of Medicinal Chemistry. 2017 Янв. 1;127:357-368. https://doi.org/10.1016/j.ejmech.2017.01.005

Author

Krasavin, Mikhail ; Lukin, Alexey ; Bagnyukova, Daria ; Zhurilo, Nikolay ; Golovanov, Aleksei ; Zozulya, Sergey ; Zahanich, Ihor ; Moore, Daniel ; Tikhonova, Irina G. / Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835. в: European Journal of Medicinal Chemistry. 2017 ; Том 127. стр. 357-368.

BibTeX

@article{bac00148019a4b42b65f27bf3a229bc2,
title = "Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835",
abstract = "A series of spirocyclic compounds inspired by Eli Lilly's phase 1 antidiabetic FFA1 receptor agonist LY2881835 was designed to include polar aromatic periphery groups and explore a possibility of building additional contacts with the target near the agonist binding site. The frontrunner compound in the series (9i) was shown to be a potent (EC50= 260 nM) FFA1 agonist with excellent aqueous (PBS) solubility and good Caco-2 permeability. The observed structure-activity relationships were rationalized by a docking study. The new series significantly expands the ligand landscape for the ongoing quest for new potent and more polar FFA1 agonists as fundamentally new class of therapeutic agents against type 2 diabetes mellitus.",
keywords = "Antidiabetic agents, Drug discovery, FFA1 agonists, Hydrophobic interactions, Spirocyclic motifs, π−π stacking",
author = "Mikhail Krasavin and Alexey Lukin and Daria Bagnyukova and Nikolay Zhurilo and Aleksei Golovanov and Sergey Zozulya and Ihor Zahanich and Daniel Moore and Tikhonova, {Irina G.}",
year = "2017",
month = jan,
day = "1",
doi = "10.1016/j.ejmech.2017.01.005",
language = "English",
volume = "127",
pages = "357--368",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835

AU - Krasavin, Mikhail

AU - Lukin, Alexey

AU - Bagnyukova, Daria

AU - Zhurilo, Nikolay

AU - Golovanov, Aleksei

AU - Zozulya, Sergey

AU - Zahanich, Ihor

AU - Moore, Daniel

AU - Tikhonova, Irina G.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - A series of spirocyclic compounds inspired by Eli Lilly's phase 1 antidiabetic FFA1 receptor agonist LY2881835 was designed to include polar aromatic periphery groups and explore a possibility of building additional contacts with the target near the agonist binding site. The frontrunner compound in the series (9i) was shown to be a potent (EC50= 260 nM) FFA1 agonist with excellent aqueous (PBS) solubility and good Caco-2 permeability. The observed structure-activity relationships were rationalized by a docking study. The new series significantly expands the ligand landscape for the ongoing quest for new potent and more polar FFA1 agonists as fundamentally new class of therapeutic agents against type 2 diabetes mellitus.

AB - A series of spirocyclic compounds inspired by Eli Lilly's phase 1 antidiabetic FFA1 receptor agonist LY2881835 was designed to include polar aromatic periphery groups and explore a possibility of building additional contacts with the target near the agonist binding site. The frontrunner compound in the series (9i) was shown to be a potent (EC50= 260 nM) FFA1 agonist with excellent aqueous (PBS) solubility and good Caco-2 permeability. The observed structure-activity relationships were rationalized by a docking study. The new series significantly expands the ligand landscape for the ongoing quest for new potent and more polar FFA1 agonists as fundamentally new class of therapeutic agents against type 2 diabetes mellitus.

KW - Antidiabetic agents

KW - Drug discovery

KW - FFA1 agonists

KW - Hydrophobic interactions

KW - Spirocyclic motifs

KW - π−π stacking

UR - http://www.scopus.com/inward/record.url?scp=85008449861&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2017.01.005

DO - 10.1016/j.ejmech.2017.01.005

M3 - Article

C2 - 28076825

AN - SCOPUS:85008449861

VL - 127

SP - 357

EP - 368

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -

ID: 34635669