Renin Inhibitors. II. Synthesis and Structure-Activity Relationships of N-Terminus Modified Inhibitors Containing a Homostatine Analogue
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概要
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The synthesis and structure-activity relationships of N-terminus modified renin inhibitors containing the homostatine analogue, (2RS, 4S, 5S)-5-amino-2-ethyl-4-hydroxy-7-methyloctanoic acid, are described. The compounds having a 3-alkyl (or aryl)sulfonylpropionyl residue at the N-terminus are found to be potent inhibitors which contain two amino acids. (2RS, 4S, 5S)-N-Isobutyl-5-[N-[(2S)-3-ethylsulfonyl-2-(1-naphthylmethyl)propionyl]-L-norleucyl]-amino-2-ethyl-4-hydroxy-7-methyloctanamie (20) has an IC_<50> of 0.5 nM against human plasma renin and the oral bioavailability of 20 is 0.73% in rats. Interaction between renin and the N-terminus of 1 and 20 is discussed in molecular modeling studies.
- 公益社団法人日本薬学会の論文
- 1992-12-25
著者
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小池 隆
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
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中野 麻喜子
Biochemistry Central Research Laboratories Banyu Pharmaceutical Co. Ltd.
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松山 研治
Biochemistry, New Drug Discovery Research Laboratories, Tsukuba Research Institute, Banyu Pharamaceu
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厚海 修吾
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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中野 真人
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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小池 隆
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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田中 誠一
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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船橋 洋
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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沢崎 芳男
Pharmacology Central Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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船橋 薫
Biochemistry Central Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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森島 甫
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd.,
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松山 研治
Biochemistry New Drug Discovery Research Laboratories Tsukuba Research Institute Banyu Pharamaceutic
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船橋 洋
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
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船橋 薫
Biochemistry Central Research Laboratories Banyu Pharmaceutical Co. Ltd.
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森島 甫
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
-
中野 真人
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
-
沢崎 芳男
Pharmacology Central Research Laboratories Banyu Pharmaceutical Co. Ltd.
-
田中 誠一
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
-
厚海 修吾
Structural Biology & Chemistry New Drug Discovery Research Laboratories Tsukuba Research Institu
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- Renin Inhibitors. III. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Dihydroxyethylene Isostere at the P_1-P_ Site
- Renin Inhibitors. II. Synthesis and Structure-Activity Relationships of N-Terminus Modified Inhibitors Containing a Homostatine Analogue
- Renin Inhibitors. I. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Homostatine Analogues at the Scissile Bond
- A New Approach to the Stereospecific Synthesis of a Dihydroxyehylene Isostere
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