Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists

Kyung Mi An; Chang Hee Hong; Hyun Jung Kwak; Shuolin Cui; Hyo Jung Song; Joon Tae Park; An Na Moon; Jeong Ah Kim; Ji Hun Yang; Jong Min Yoon; Myong Jae Lee; Dong Gu Jeong; Dohee Kim; Don Gil Lee; Jeong Cheol Shin; In Gyu Je; Hong Sub Lee; Soobong Park; Jae Hoon Kang; Soo Young Ko

doi:10.1002/bkcs.11185

Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists

Kyung Mi An, Chang Hee Hong, Hyun Jung Kwak, Shuolin Cui, Hyo Jung Song, Joon Tae Park, An Na Moon, Jeong Ah Kim, Ji Hun Yang, Jong Min Yoon, Myong Jae Lee, Dong Gu Jeong, Dohee Kim, Don Gil Lee, Jeong Cheol Shin, In Gyu Je, Hong Sub Lee, Soobong Park, Jae Hoon Kang, Soo Young Ko

Department of Chemistry & Nanoscience

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

3 Scopus citations

Abstract

GPR40 (G protein-coupled receptor 40) has become an attractive target for insulin secretagogue via glucose-dependent mechanism with low risk of hypoglycemia. In order to overcome problems associated with previously developed GPR40 agonists, we recruited the core fragment 2,3-dihydro-1H-indene to GPR40 receptor binding pharmacophore with carboxylic acid moiety, and screened various amine analogs to finally discover several hit compounds displaying GPR40 agonistic activities. Through additional in vitro ADME, pharmacokinetics, and in vivo efficacy evaluations, compound 1e was demonstrated as a potent lead GPR40 agonist.

Original language	English
Pages (from-to)	861-868
Number of pages	8
Journal	Bulletin of the Korean Chemical Society
Volume	38
Issue number	8
DOIs	https://doi.org/10.1002/bkcs.11185
State	Published - Aug 2017

Bibliographical note

Publisher Copyright:
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

GPR40
Glucose-stimulated insulin secretion
Hypoglycemia
Insulin secretagogue

Access to Document

10.1002/bkcs.11185

Cite this

An, K. M., Hong, C. H., Kwak, H. J., Cui, S., Song, H. J., Park, J. T., Moon, A. N., Kim, J. A., Yang, J. H., Yoon, J. M., Lee, M. J., Jeong, D. G., Kim, D., Lee, D. G., Shin, J. C., Je, I. G., Lee, H. S., Park, S., Kang, J. H., & Ko, S. Y. (2017). Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists. Bulletin of the Korean Chemical Society, 38(8), 861-868. https://doi.org/10.1002/bkcs.11185

@article{78bd38d9e7154968bb7390d4f91a15ef,

title = "Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists",

abstract = "GPR40 (G protein-coupled receptor 40) has become an attractive target for insulin secretagogue via glucose-dependent mechanism with low risk of hypoglycemia. In order to overcome problems associated with previously developed GPR40 agonists, we recruited the core fragment 2,3-dihydro-1H-indene to GPR40 receptor binding pharmacophore with carboxylic acid moiety, and screened various amine analogs to finally discover several hit compounds displaying GPR40 agonistic activities. Through additional in vitro ADME, pharmacokinetics, and in vivo efficacy evaluations, compound 1e was demonstrated as a potent lead GPR40 agonist.",

keywords = "GPR40, Glucose-stimulated insulin secretion, Hypoglycemia, Insulin secretagogue",

author = "An, {Kyung Mi} and Hong, {Chang Hee} and Kwak, {Hyun Jung} and Shuolin Cui and Song, {Hyo Jung} and Park, {Joon Tae} and Moon, {An Na} and Kim, {Jeong Ah} and Yang, {Ji Hun} and Yoon, {Jong Min} and Lee, {Myong Jae} and Jeong, {Dong Gu} and Dohee Kim and Lee, {Don Gil} and Shin, {Jeong Cheol} and Je, {In Gyu} and Lee, {Hong Sub} and Soobong Park and Kang, {Jae Hoon} and Ko, {Soo Young}",

note = "Publisher Copyright: {\textcopyright} 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2017",

month = aug,

doi = "10.1002/bkcs.11185",

language = "English",

volume = "38",

pages = "861--868",

journal = "Bulletin of the Korean Chemical Society",

issn = "0253-2964",

publisher = "Wiley-Blackwell",

number = "8",

}

An, KM, Hong, CH, Kwak, HJ, Cui, S, Song, HJ, Park, JT, Moon, AN, Kim, JA, Yang, JH, Yoon, JM, Lee, MJ, Jeong, DG, Kim, D, Lee, DG, Shin, JC, Je, IG, Lee, HS, Park, S, Kang, JH & Ko, SY 2017, 'Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists', Bulletin of the Korean Chemical Society, vol. 38, no. 8, pp. 861-868. https://doi.org/10.1002/bkcs.11185

TY - JOUR

T1 - Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists

AU - An, Kyung Mi

AU - Hong, Chang Hee

AU - Kwak, Hyun Jung

AU - Cui, Shuolin

AU - Song, Hyo Jung

AU - Park, Joon Tae

AU - Moon, An Na

AU - Kim, Jeong Ah

AU - Yang, Ji Hun

AU - Yoon, Jong Min

AU - Lee, Myong Jae

AU - Jeong, Dong Gu

AU - Kim, Dohee

AU - Lee, Don Gil

AU - Shin, Jeong Cheol

AU - Je, In Gyu

AU - Lee, Hong Sub

AU - Park, Soobong

AU - Kang, Jae Hoon

AU - Ko, Soo Young

PY - 2017/8

Y1 - 2017/8

N2 - GPR40 (G protein-coupled receptor 40) has become an attractive target for insulin secretagogue via glucose-dependent mechanism with low risk of hypoglycemia. In order to overcome problems associated with previously developed GPR40 agonists, we recruited the core fragment 2,3-dihydro-1H-indene to GPR40 receptor binding pharmacophore with carboxylic acid moiety, and screened various amine analogs to finally discover several hit compounds displaying GPR40 agonistic activities. Through additional in vitro ADME, pharmacokinetics, and in vivo efficacy evaluations, compound 1e was demonstrated as a potent lead GPR40 agonist.

AB - GPR40 (G protein-coupled receptor 40) has become an attractive target for insulin secretagogue via glucose-dependent mechanism with low risk of hypoglycemia. In order to overcome problems associated with previously developed GPR40 agonists, we recruited the core fragment 2,3-dihydro-1H-indene to GPR40 receptor binding pharmacophore with carboxylic acid moiety, and screened various amine analogs to finally discover several hit compounds displaying GPR40 agonistic activities. Through additional in vitro ADME, pharmacokinetics, and in vivo efficacy evaluations, compound 1e was demonstrated as a potent lead GPR40 agonist.

KW - GPR40

KW - Glucose-stimulated insulin secretion

KW - Hypoglycemia

KW - Insulin secretagogue

UR - http://www.scopus.com/inward/record.url?scp=85026789295&partnerID=8YFLogxK

U2 - 10.1002/bkcs.11185

DO - 10.1002/bkcs.11185

M3 - Article

AN - SCOPUS:85026789295

SN - 0253-2964

VL - 38

SP - 861

EP - 868

JO - Bulletin of the Korean Chemical Society

JF - Bulletin of the Korean Chemical Society

IS - 8

ER -

Discovery of 2,3-Dihydro-1H-indene Derivatives as Novel GPR40 Agonists

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this