Document Detail


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.
MedLine Citation:
PMID:  19926281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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:
Type:  Journal Article     Date:  2009-10-29
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  341-5     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co. Ltd, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. uto.yoshikazu.pw@daiichisankyo.co.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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


Previous Document:  Reaction of naphthoquinones with substituted nitromethanes. Facile synthesis and antifungal activity...
Next Document:  Improving the developability profile of pyrrolidine progesterone receptor partial agonists.