Discovery of novel pyrrole derivatives as potent agonists for the niacin receptor GPR109A.


Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 05 2020
Historique:
received: 29 12 2019
revised: 23 02 2020
accepted: 08 03 2020
pubmed: 23 3 2020
medline: 1 5 2021
entrez: 23 3 2020
Statut: ppublish

Résumé

Novel pyrrole derivatives were discovered as potent agonists of the niacin receptor, GPR109A. During the derivatization, compound 16 was found to be effective both in vitro and in vivo. The compound 16 exhibited a significant reduction of the non-esterified fatty acid in human GPR109A transgenic rats, and the duration of its in vivo efficacy was much longer than niacin.

Identifiants

pubmed: 32199732
pii: S0960-894X(20)30194-3
doi: 10.1016/j.bmcl.2020.127105
pii:
doi:

Substances chimiques

Fatty Acids, Nonesterified 0
HCAR2 protein, human 0
Nicotinic Agonists 0
Pyrroles 0
Receptors, G-Protein-Coupled 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

127105

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Yuriko Miyazawa (Y)

External Affairs Department, Daiichi Sankyo Co., Ltd., Nihonbashi-honcho, Chuo-ku, Tokyo 103-8426, Japan. Electronic address: miyazawa.yuriko.kv@daiichisankyo.co.jp.

Takahiro Yamaguchi (T)

Modality Research Laboratories, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Mitsuhiro Yamaguchi (M)

R&D Planning & Management Department, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Keiko Tago (K)

Medicinal Chemistry Research Laboratories, Daiichi Sankyo RD Novare Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Akihiro Tamura (A)

Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.

Daisuke Sugiyama (D)

Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Takahide Aburatani (T)

Modality Research Laboratories, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Tomohiro Nishizawa (T)

External Affairs Department, Daiichi Sankyo Co., Ltd., Nihonbashi-honcho, Chuo-ku, Tokyo 103-8426, Japan.

Nobuya Kurikawa (N)

Specialty Medicine Research Laboratories II, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Keita Kono (K)

Specialty Medicine Research Laboratories I, Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

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Classifications MeSH