Synthesis of 1-Benzothiepine and 1-Benzazepine Derivatives as Orally Active CCR5 Antagonists
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概要
- 論文の詳細を見る
Quaternary ammonium benzocycloheptene compound I has previously been reported as a clinical candidate for an injectable CCR5 antagonist. In order to develop an orally active CCR5 antagonist, derivatives of tertiary amine benzocycloheptene 2, the chemical precursor to 1, were investigated. The benzocycloheptene ring was converted to benzothiepine and benzazepine rings and it was found that these changes could enhance the potency of tertiary amine derivatives. In particular, the 1-benzothiepine-1,1-dioxide 11b and the N-methyl-1-benzazepine 18 showed increased activity and good preliminary pharmacokinetic properties. The synthesis of 1-benzothiepine and 1-benzazepine derivatives and their activity are described.
- 公益社団法人日本薬学会の論文
- 2004-02-01
著者
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KANZAKI Naoyuki
Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
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Shiraishi Mitsuru
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Shiraishi Mitsuru
Pharmaceutical Research Laboratories Ii Takeda Chemical Industries Ltd.
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Shiraishi Mitsuru
Pharmaceutical Research Laboratories Ii Pharmaceutical Research Division Takeda Chemical Industries
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Kanzaki Naoyuki
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
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Kanzaki Naoyuki
Takeda Chemical Industries Ltd. Pharmaceutical Research Division
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SETO Masaki
Medicinal Chemistry Research Laboratries, Pharmaceutical Research Division, Takeda Chemical Industri
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ARAMAKI Yoshio
Medicinal Chemistry Research Laboratries, Pharmaceutical Research Division, Takeda Chemical Industri
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ODA Tsuneo
Medicinal Chemistry Research Laboratries, Pharmaceutical Research Division, Takeda Chemical Industri
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OKAWA Tomohiro
Medicinal Chemistry Research Laboratries, Pharmaceutical Research Division, Takeda Chemical Industri
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Oda T
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Seto M
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Aramaki Y
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Okawa Tomohiro
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Shiraishi M
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Seto Masaki
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industrie
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Aramaki Yoshio
Medicinal Chemistry Research Laboratories Pharmaceutical Research Division Takeda Chemical Industries Ltd
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