Synthesis and evaluation of a novel 2-azabicyclo[2.2.2]octane class of long chain fatty acid elongase 6 (ELOVL6) inhibitors

被引：3

作者：

Sasaki, Takahide ^{[1
]}

Nagase, Tsuyoshi ^{[1
]}

Takahashi, Toshiyuki ^{[1
]}

Nagumo, Akira ^{[1
]}

Shimamura, Ken ^{[1
]}

Miyamoto, Yasuhisa ^{[1
]}

Kitazawa, Hidefumi ^{[1
]}

Kanesaka, Maki ^{[1
]}

Yoshimoto, Ryo ^{[1
]}

Aragane, Katsumi ^{[1
]}

Tokita, Shigeru ^{[1
]}

Sato, Nagaaki ^{[1
,2
]}

机构：

[1] Banyu Pharmaceut Co Ltd, Merck Res Labs, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

[2] Taisho Pharmaceut Co Ltd, Taisho Res Labs, Kita Ku, Saitama 3319530, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 15期

关键词：

Long chain fatty acid elongase 6 inhibitor; 2-Azabicyclo[2.2.2]octane; Anti-diabetic agent; Lipogenesis; ACYL-COA ELONGASE; ADIPOSE-TISSUE; GENE FAMILY; IDENTIFICATION; METABOLISM; CLONING;

D O I：

10.1016/j.bmc.2009.06.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel 2-azabicyclo[2.2.2]octane derivatives was synthesized and evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Screening of our corporate chemical collections against ELOVL6 resulted in the identification of lead 1. Exploratory chemistry efforts were applied to lead 1 to identify the orally available, potent, and selective ELOVL6 inhibitor 28a. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5639 / 5647

页数：9

共 24 条

[1] Synthesis and Evaluation of a Novel Indoledione Class of Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors
Takahashi, Toshiyuki
Nagase, Tsuyoshi
Sasaki, Takahide
Nagumo, Akira
Shimamura, Ken
Miyamoto, Yasuhisa
Kitazawa, Hidefumi
Kanesaka, Maki
Yoshimoto, Ryo
Aragane, Katsurni
Tokita, Shigeru
Sato, Nagaaki
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (10) : 3142 - 3145
[2] Synthesis and Biological Evaluation of a Novel 3-Sulfonyl-8-azabicyclo[3.2.1]octane Class of Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors
Nagase, Tsuyoshi
Takahashi, Toshiyuki
Sasaki, Takahide
Nagumo, Akira
Shimamura, Ken
Miyamoto, Yasuhisa
Kitazawa, Hidefumi
Kanesaka, Maki
Yoshimoto, Ryo
Araganc, Katsumi
Tokita, Shigeru
Sato, Nagaaki
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (14) : 4111 - 4114
[3] Quantitative Structure Activity Relationship Studies on a Novel Indolediones as Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors
Zheng, Junxia
Wu, Zhiwei
Dai, Mibei
Xu, Zhihui
Li, Xiaomei
Zhu, Shanshan
Lin, Chuyun
Hu, Peijian
Zhang, Luo
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Zhao, Suqing
Zhang, Kun
Sun, Pinghua
LETTERS IN DRUG DESIGN & DISCOVERY, 2011, 8 (05) : 422 - 429
[4] Discovery of Novel Benzoxazinones as Potent and Orally Active Long Chain Fatty Acid Elongase 6 Inhibitors
Mizutani, Takashi
Ishikawa, Shiho
Nagase, Tsuyoshi
Takahashi, Hidekazu
Fujimura, Takashi
Sasaki, Takahide
Nagumo, Akira
Shimamura, Ken
Miyamoto, Yasuhisa
Kitazawa, Hidefumi
Kanesaka, Maki
Yoshimoto, Ryo
Aragane, Katsumi
Tokita, Shigeru
Sato, Nagaaki
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (22) : 7289 - 7300
[5] Long-Chain Fatty Acid Elongase, Elovl6 is Crucial for Vascular Smooth Muscle Cell Proliferation Underlying Neointimal Hyperplasia
Sunaga, Hiroaki
Matsui, Hiroki
Yokoyama, Tomoyuki
Anjo, Saki
Iso, Tatsuya
Kurabayashi, Masahiko
CIRCULATION, 2012, 126 (21)
[6] Molecular characterization of elongase of very long-chain fatty acids 6 (elovl6) genes in Misgurnus anguillicaudatus and their potential roles in adaptation to cold temperature
Chen, Jingwen
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[7] Discovery of brain permeable 2-Azabicyclo[2.2.2]octane sulfonamides as a novel class of presenilin-1 selective γ-secretase inhibitors
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 260
[8] Two Modes of Regulation of the Fatty Acid Elongase ELOVL6 by the 3-Ketoacyl-CoA Reductase KAR in the Fatty Acid Elongation Cycle
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Kihara, Akio
PLOS ONE, 2014, 9 (07):
[9] Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance
Moon, Young-Ah
Ochoa, Courtney R.
Mitsche, Matthew A.
Hammer, Robert E.
Horton, Jay D.
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[10] Fatty acid elongase 6 plays a role in the synthesis of long-chain fatty acids in goat mammary epithelial cells
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Wu, M.
Zhu, J. J.
Zhang, C. H.
Yao, D. W.
Luo, J.
Loor, J. J.
JOURNAL OF DAIRY SCIENCE, 2017, 100 (06) : 4987 - 4995

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