Structure-Activity Relationship Studies of 3-or 4-Pyridine Derivatives of DS-6930

被引：4

作者：

Shinozuka, Tsuyoshi ^{[1
]}

Tsukada, Tomoharu ^{[1
]}

Fujii, Kunihiko ^{[1
]}

Tokumaru, Eri ^{[1
]}

Matsui, Yumi ^{[2
]}

Wakimoto, Satoko ^{[1
]}

Ogata, Tsuneaki ^{[1
]}

Araki, Kazushi ^{[1
]}

Sawamura, Ryoko ^{[1
]}

Watanabe, Nobuaki ^{[1
]}

Mori, Makoto ^{[1
]}

Tanaka, Jun ^{[1
]}

机构：

[1] Daiichi Sankyo Co Ltd, R&D Div, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan

[2] Daiichi Sankyo RD Novare Co Ltd, R&D Div, Edogawa Ku, 1-16-13 Kitakasai, Tokyo 1348630, Japan

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2019年 / 10卷 / 03期

关键词：

DS-6930; benzoic acid; benzimidazole; PPAR gamma; partial agonist;

D O I：

10.1021/acsmedchemlett.8b00645

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Derivatization efforts were continued to discover backups for a potent selective PPAR gamma modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modifications of benzimidazole ring were explored to discover potent intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed to show potent efficacy in vivo, whereas 7'-fluoro benzimidazole 3g (DS19161384) was found to result in robust plasma glucose reductions with excellent DMPK profiles.

引用

页码：358 / 362

页数：9

共 50 条

[1] STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF PHENCYCLIDINE DERIVATIVES IN RATS
CONE, EJ
MCQUINN, RL
SHANNON, HE
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 1984, 228 (01): : 147 - 153
[2] Structure-activity relationship studies of 4-methylcoumarin derivatives as anticancer agents
Miri, Ramin
Nejati, Maryam
Saso, Luciano
Khakdan, Fatemeh
Parshad, Badri
Mathur, Divya
Parmar, Virinder S.
Bracke, Marc E.
Prasad, Ashok K.
Sharma, Sunil K.
Firuzi, Omidreza
PHARMACEUTICAL BIOLOGY, 2016, 54 (01) : 105 - 110
[3] Structure activity relationship studies on the pyridine derivatives as CGRP antagonists
Luo, Guanglin
Chen, Ling
Civiello, Rita
Pin, Sokhom
Xu, Cen
Kostich, Walter A.
Cook, Deborah
Signor, Laura
Macci, Robert
Davies, Carl
Conway, Charles M.
Macor, John E.
Dubowchik, Gene
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
[4] Synthesis of Ureidomuraymycidine Derivatives for Structure-Activity Relationship Studies of Muraymycins
Aleiwi, Bilal A.
Schneider, Christopher M.
Kurosu, Michio
JOURNAL OF ORGANIC CHEMISTRY, 2012, 77 (08): : 3859 - 3867
[5] STRUCTURE ACTIVITY RELATIONSHIP OF PYRIDINE DERIVATIVES
PASKOV, D
SPASOV, A
KRUSHKOV, I
GOLOVINSKY, E
ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE, 1965, 157 (01): : 132 - +
[6] Structure-Activity Relationship of Niclosamide Derivatives
Tang, Zhonghai
Acuna, Ulyana Munoz
Fernandes, Nelson Freitas
Chettiar, Somsundaram
Li, Pui-Kai
De Blanco, Esperanza Carcache
ANTICANCER RESEARCH, 2017, 37 (06) : 2839 - 2843
[7] Antiplasmodial activity, structure-activity relationship and studies on the action of novel benzimidazole derivatives
Escala, Nerea
Pineda, Laura M.
Ng, Michelle G.
Coronado, Lorena M.
Spadafora, Carmenza
del Olmo, Esther
SCIENTIFIC REPORTS, 2023, 13 (01)
[8] Quantitative structure-activity relationship of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives with AT1 receptor antagonistic activity
Jiang Yu-ren
Chen Yu-ling
Yang Yan-yan
Liu Qiang
JOURNAL OF CENTRAL SOUTH UNIVERSITY OF TECHNOLOGY, 2012, 19 (05): : 1212 - 1218
[9] Quantitative structure-activity relationship of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives with AT1 receptor antagonistic activity
蒋玉仁
陈玉玲
杨焱焱
刘强
JournalofCentralSouthUniversity, 2012, 19 (05) : 1212 - 1218
[10] Quantitative structure-activity relationship of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives with AT1 receptor antagonistic activity
Yu-ren Jiang
Yu-ling Chen
Yan-yan Yang
qiang Liu
Journal of Central South University, 2012, 19 : 1212 - 1218

← 1 2 3 4 5 →