Synthesis of N-substituted C-normorphinans and their pharmacological properties. |
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Authors: | M Takeda H Inoue K Noguchi Y Honma K Okamura T Date S Nurimoto M Yamamura S Saito |
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Institution: | Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan. |
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Abstract: | 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. |
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