Synthesis and Biological Evaluation of 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent and Selective M_2 Muscarinic Receptor Antagonists

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概要

• 論文の詳細を見る

• A series of 1,2,3,4-tetrahydroisoquinoline derivatives containing the 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton were prepared and evaluated for their in vitro binding affinities to muscarinic receptors and for antagonism of bradycardia in vivo. Among them, compound 3f had the highest affinity for M_2 muscarinic receptors in the heart (pKi=9.1) with low affinity for M_3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the benzene ring fused piperidine and the alkyl linker chain lenght are crucially important for increased M_2 affinity.

• 公益社団法人日本薬学会の論文
• 1999-05-15

著者

• Takizawa Kayoko

  Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University

• 渡辺 敏子

  School Of Pharmaceutical Sciences Toho University

• Watanabe Toshifumi

  Pharmaceutical Research Laboratories Ii Pharmaceutical Research Division Takeda Chemical Industries

• SHIBANUMA Tadao

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• Takizawa Kayoko

  Res. Center For Pathogenic Fungi And Microbial Toxicoses Chiba Univ.

• Watanabe T

  Chiba Univ. Chiba Jpn

• Watanabe Toshiko

  Faculty Of Pharmaceutical Sciences Chiba University

• Watanabe Toshiko

  Graduate School Of Pharmaceutical Sciences Chiba University

• Watanabe Toshihiro

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Takizawa K

  Res. Center For Pathogenic Fungi And Microbial Toxicoses Chiba Univ.

• Shibanuma Tadao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• KINOYAMA Isao

  Institute for Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• HIRANO Seiko

  Institute for Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• Hirano S

  The Nukada Institute For Medical And Biological Research

• Kinoyama Isao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• TAKIZAWA Kenji

  Clinical Development Division, Yamanouchi Pharmaceutical Co.,

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