| Discovery of a new chemical lead for a matrix metalloproteinase inhibitor. | |
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MedLine Citation:
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PMID: 16481176 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of N-benzoyl gamma-aminobutyric hydroxamic acids were synthesized and evaluated as matrix metalloproteinase inhibitors. First, we focused on chemical modification of the N-benzoyl residue. Introduction of electron-rich para-substituents was effective to increase the inhibitory activity. Especially, some of the analogs with relatively more planar N-acyl residues, such as 10 and 11, demonstrated more potent activity. Second, chemical modification of the gamma-aminobutyric hydroxamic acid moiety was carried out to optimize the three-dimensional arrangement of the two pharmacophores (hydroxamic acid and N-acyl residues). Among the tested, the gamma-aminobutyric hydroxamic acid moiety was found to be the best spacer for connecting the above-mentioned two pharmacophores. Synthesis and structure-activity relationships are discussed. |
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Authors:
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Masahiro Ikura; Shingo Nakatani; Shingo Yamamoto; Hiromu Habashita; Tsuneyuki Sugiura; Kanji Takahashi; Koji Ogawa; Hiroyuki Ohno; Hisao Nakai; Masaaki Toda |
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Publication Detail:
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Type: Journal Article Date: 2006-02-14 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 14 ISSN: 0968-0896 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-08 Completed Date: 2006-08-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 4241-52 Citation Subset: IM |
Affiliation:
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Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. ikura@ono.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Drug Design Enzyme Inhibitors / chemical synthesis, chemistry*, pharmacology* Humans Matrix Metalloproteinases / antagonists & inhibitors* Molecular Structure Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; EC 3.4.24.-/Matrix Metalloproteinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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