In silico design of bioisosteric modifications of drugs for the treatment of diabetes

Guillaume Vink; Jean Christophe Nebel; Stephen P. Wren

doi:10.4155/fmc-2020-0374

In silico design of bioisosteric modifications of drugs for the treatment of diabetes

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Abstract

Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials & methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.

Original language	English
Pages (from-to)	691-700
Journal	Future Medicinal Chemistry
Volume	13
Issue number	8
Early online date	10 Mar 2021
DOIs	https://doi.org/10.4155/fmc-2020-0374
Publication status	Published - Apr 2021

Bibliographical note

Note: This work was supported by the Erasmus+ programme of the European Union.

Keywords

Chemistry
GPR40 agonist
bioisosteres
docking
drug design
preliminary communication
type 2 diabetes

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10.4155/fmc-2020-0374

Wren-S-48315-AAMAccepted author manuscript, 1.27 MBLicence: Unspecified
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https://doi.org/10.4155/fmc-2020-0374

Protein Bioinformatics: Structure and Function
Nebel, J.-C. (PI), Abbass, J. (CoI), Esmaielbeiki, R. (Researcher), Laibe, J. (Researcher), Dyrka, W. (Researcher), Kotulska, M. (CoI) & Konopka, B. M. (Researcher)
7/06/04 → 10/12/21
Project: Research

Cite this

@article{4e7b1a4f96e042bc9456c8073a8fb267,

title = "In silico design of bioisosteric modifications of drugs for the treatment of diabetes",

abstract = "Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials \& methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.",

keywords = "Chemistry, GPR40 agonist, bioisosteres, docking, drug design, preliminary communication, type 2 diabetes",

author = "Guillaume Vink and Nebel, \{Jean Christophe\} and Wren, \{Stephen P.\}",

note = "Note: This work was supported by the Erasmus+ programme of the European Union.",

year = "2021",

month = apr,

doi = "10.4155/fmc-2020-0374",

language = "English",

volume = "13",

pages = "691--700",

journal = "Future Medicinal Chemistry",

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T1 - In silico design of bioisosteric modifications of drugs for the treatment of diabetes

AU - Vink, Guillaume

AU - Nebel, Jean Christophe

AU - Wren, Stephen P.

N1 - Note: This work was supported by the Erasmus+ programme of the European Union.

PY - 2021/4

Y1 - 2021/4

N2 - Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials & methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.

AB - Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials & methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.

KW - Chemistry

KW - GPR40 agonist

KW - bioisosteres

KW - docking

KW - drug design

KW - preliminary communication

KW - type 2 diabetes

U2 - 10.4155/fmc-2020-0374

DO - 10.4155/fmc-2020-0374

M3 - Article

SN - 1756-8919

VL - 13

SP - 691

EP - 700

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

IS - 8

ER -

In silico design of bioisosteric modifications of drugs for the treatment of diabetes

Abstract

Bibliographical note

Keywords

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Protein Bioinformatics: Structure and Function

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