Pharmacological characterization of a novel sulfonylureid-pyrazole derivative, SM-19712, a potent nonpeptide inhibitor of endothelin converting enzyme
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- Umekawa Kayo
- Discovery Research Laboratories I,Research Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Hasegawa Hirohiko
- Discovery Research Laboratories I,Research Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Tsutsumi Yasushi
- Discovery Research Laboratories I,Research Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Sato Kimihiko
- Discovery Research Laboratories I,Research Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Matsumura Yasuo
- Department of Pharmacology,Osaka University of Pharmaceutical Sciences,Osaka 569-1094,Japan
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- Ohashi Naohito
- Discovery Research Laboratories I,Research Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
書誌事項
- タイトル別名
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- Pharmacological Characterization of a Novel Sulfonylureid-Pyrazole Derivative, SM-19712, a Potent Nonpeptidic Inhibitor of Endothelin Converting Enzyme.
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We describe the pharmacological characteristics of SM−19712 {4−chloro−N−[[(4−cyano−3−methyl−1−phenyl−1H−pyrazol−5−yl)amino]carbonyl]benzenesulfonamide, monosodium salt}.SM−19712 inhibited endothelin converting enzyme(ECE)solubilized from rat lung microsomes with an IC50 value of 42 nM and, at 10−100μM, had no effect on other metalloproteases such as neutral endopeptidase 24.11 and angiotensin converting enzyme, showing a high specificity for ECE.In cultured porcine aortic endothelial cells, SM−19712 at 1−100μM concentration−dependently inhibited the endogenous conversion of big endothelin−1(ET−1)to ET−1 with an IC50 value of 31μM.In anesthetized rats, either intravenous(1−30 mg/kg)or oral(10−30 mg/kg)administration of SM−19712 dose−dependently suppressed the pressor responses induced by big ET−1.In acute myocardial infarction of rabbits subjected to coronary occlusion and reperfusion, SM−19712 reduced the infarct size, the increase in serum concentration of ET−1 and the serum activity of creatinine phosphokinase.The present study demonstrates that SM−19712 is a structurally novel, nonpeptide, potent and selective inhibitor of ECE, and SM−19712 is a valuable new tool for elucidating the pathophysiological role of ECE.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 84 (1), 7-15, 2000
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282679261926016
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- NII論文ID
- 10008184942
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- NII書誌ID
- AA00691188
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- DOI
- 10.1254/jjp.84.7
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- COI
- 1:CAS:528:DC%2BD3cXmvVyrur0%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 5526002
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- PubMed
- 11043447
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I5526002
- https://api.elsevier.com/content/article/PII:S0021519819305426?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819305426?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/84/1/84_1_7/_pdf
- https://search.jamas.or.jp/link/ui/2001025610
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- 本文言語コード
- en
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- JaLC
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