Structure-Activity Relationship of Orally Potent Tripeptide-Based HIV Protease Inhibitors Containing Hydroxymethylcarbonyl Isostere
スポンサーリンク
概要
- 論文の詳細を見る
We designed and synthesized a new class of peptidomimetic human immunodeficiency virus protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl isostere as the active moiety. From a structure-activity relationship study of HIV-1 protease inhibition, enzyme selectivity for other aspartyl proteases, the antiviral activity and pharmacokinetics in rats, 24c (KNI-227) and 24d (KNI-272,our first clinical candidate) were found to be selective and orally potent HIV protease inhibitors. Moreover, an improvement of the pharmacokinetic features of KNI-272 provided two long-lasting and highly bioavailable compounds (24g : JE-2178,24h : JE-2179).
- 公益社団法人日本薬学会の論文
- 2000-09-01
著者
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Kiso Y
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Nojima Satoshi
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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KISO Yoshiaki
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Centur
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HAYASHI Hideya
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation
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Hayashi H
Univ. Tokyo Tokyo Jpn
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Kato Ryohei
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Ueno Takamasa
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Tanaka Shigeki
Department Of Surgery Yokohama City University Hospital And School Of Medicine
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Hayashi H
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Hayashi Hideya
Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation
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Hayashi H
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Hayashi Hideya
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Hattori N
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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TERASHIMA Keisuke
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd.
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TAKAKU Haruo
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd.
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SHINTANI Makoto
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd.
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MISAWA Satoru
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation
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TAKAKU Haruo
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation
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MIMOTO Tsutomu
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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HATTORI Naoko
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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KISANUKI Sumitsugu
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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FUKAZAWA Tominaga
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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TERASHIMA Keisuke
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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NOJIMA Satoshi
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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IMAI Junya
Department of Medicinal Chemistry, Kyoto Pharmaceutical University
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ENOMOTO Hiroshi
Department of Medicinal Chemistry, Kyoto Pharmaceutical University
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SAKIKAWA Hiroshi
Department of Medicinal Chemistry, Kyoto Pharmaceutical University
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SHINTANI Makoto
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation
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Nojima Satoshi
Pesticide Research Institute Faculty Of Agriculture Kyoto University
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Enomoto Hiroshi
Department Of Mechanical Engineering Osaka Prefecture University
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Enomoto Hiroshi
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Imai Junya
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Takaku H
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Kiso Yoshiaki
Department Of Medicinal Chemistry Center For Frontier Research In Medicinal Science 21st Century Coe
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Misawa Satoru
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Misawa S
Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation
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Nakata Shingo
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Mimoto Tsutomu
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Sakikawa H
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Takaku Haruo
Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation
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Shintani M
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Terashima Keisuke
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Fukazawa Tominaga
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation
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Enomoto H
Department Of Mechanical Engineering Osaka Prefecture University
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Tanaka Shigeki
Department Of Applied Chemistry Tokai University
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Tanaka Shigeki
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Kisanuki S
Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation:department Of Medicinal Chem
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KISO Yoshiaki
Department of Ecological Engineering, Toyohashi University of Technology, JAPAN.
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