Synthesis of N-Substituted C-Normorphinans and Their Pharmacological Properties

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概要

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• Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested for their analgetic and narcotic antagonist activities and physical dependence capacity. Treatment of N-formyl-octahydro-2-pyrindine (IIIc) with polyphosphoric acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII) obtained from IV were converted to VIII and IX. The N-methyl derivative (I), which was previously reported to be inactive by Haffner's method, exhibited potent analgetic activity by the hot plate method and the AcOH-induced writhing test. Compounds VIII and IX showed pharmacological properties similar to those of N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited potent analgetic and antagonist activities with no physical dependence capacity in the single-dose suppression tests both in rats and monkeys.

• 1992-05-25

著者

• 井上 博純

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd, .

• 武田 幹男

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• 岡村 公生

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• 伊達 忠正

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• 本間 靖

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.

• 野口 勝通

  Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.

• 斎藤 清一

  Organic Chemistry Research Laboratory

• 斉藤 清一

  田辺製薬研

• 斎藤 清一

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• 岡村 公生

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• 塗本 精一

  Safety Research Laboratory Tanabe Seiyaku Co. Ltd.

• 山村 道夫

  Safety Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• 本間 靖

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• 武田 幹男

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• 伊達 忠正

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• 井上 博純

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd .

• 山村 道夫

  Safety Reseach Laboratory:tanabe Seiyaku Co. Ltd.

• 山村 道夫

  Safety Research Laboratory Tanabe Seiyaku Co. Ltd.

• 野口 勝通

  Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd. :(present Address)sapporo Branch Tanab

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