| Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats. | |
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MedLine Citation:
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PMID: 19926281 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd). |
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Authors:
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Yoshikazu Uto; Tsuneaki Ogata; Yohei Kiyotsuka; Yuko Ueno; Yuriko Miyazawa; Hitoshi Kurata; Tsuneo Deguchi; Nobuaki Watanabe; Masahiro Konishi; Ryo Okuyama; Nobuya Kurikawa; Toshiyuki Takagi; Satoko Wakimoto; Jun Ohsumi |
Publication Detail:
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Type: Journal Article Date: 2009-10-29 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-05-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 341-5 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co. Ltd, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. uto.yoshikazu.pw@daiichisankyo.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Enzyme Inhibitors / chemical synthesis, chemistry*, pharmacokinetics Humans Hypoglycemic Agents / chemical synthesis, chemistry*, pharmacokinetics Mice Microsomes, Liver / metabolism Piperidines / chemical synthesis, chemistry*, pharmacokinetics Pyridazines / chemical synthesis, chemistry*, pharmacology Pyridines / chemical synthesis, chemistry*, pharmacology Rats Rats, Zucker Stearoyl-CoA Desaturase / antagonists & inhibitors*, metabolism Triglycerides / blood* |
| Chemical | |
Reg. No./Substance:
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0/6-(4-(2-methylbenzoyl)piperidin-1-yl)pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide; 0/Enzyme Inhibitors; 0/Hypoglycemic Agents; 0/Piperidines; 0/Pyridazines; 0/Pyridines; 0/Triglycerides; EC 1.14.19.1/Stearoyl-CoA Desaturase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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