Novel 5-Hydroxytryptamine 4 (5-HT_4) Receptor Agonists. Synthesis and Gastroprokinetic Activity of 4-Amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamides

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概要

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• A novel series of 4-amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamide derivatives (1), which had amines conformationally restricted due to the effect of repulsion by neighboring substituents, were prepared and evaluated for 5-hydroxytryptamine 4 (5-HT_4) agonistic activities by using the contraction of longitudinal muscle myenteric plexus (LMMP) of guinea pig ileum. One of the most potent compounds in this series was 4-amino-5-chloro-N-[2-(1-dimethylamino-1-cyclohexyl)ethyl]-2-methoxybenzamide (1c, YM-47813) with an EC<50> value of 1.0 μM on LMMP. This compound effectively enhanced gastric motility and gastric emptying in conscious dogs by oral administration (1-3 mg/kg).

• 公益社団法人日本薬学会の論文
• 1998-07-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• SUZUKI Takeshi

  Institute for Solid State Physics, University of Tokyo

• Miyata K

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Miyata K

  Yamanouchi Pharmaceutical Co. Ltd. Tsukuba City Jpn

• Miyata Keiji

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Miyata Keiji

  Inflammation Research Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pha

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• 鈴木 徳治

  千葉大 薬

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Ohta Masato

  Pharmaceutical Research Center Meiji Seika Kaisha Ltd.

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• WATANUKI Susumu

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

• Ohta Miyako

  Division Of Biological Chemistry And Biologicals National Institute Of Health Sciences

• Miyata K

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Yamagiwa Yoko

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Watanuki Susumu

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Miyata K

  Inflammation Research Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pha

• NAKAHARA Hideaki

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

• MASE Toshiyasu

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

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Nakahara H

  Graduate School Of Science And Engineering Saitama University

• IMANISHI Naoki

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

• OHTA Mitsuaki

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

• ITAHANA Hirotsune

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

• Imanishi N

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Miyata K

  Hitachi Research Laboratory Hitachi Ltd.

• Mase T

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Nakahara Hideaki

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Itahana Hirotsune

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Suzuki Takeshi

  Institute For Molecular And Cellular Regulation Gunma University

• Hirotsune Itahana

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

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