Synthesis of N-substituted C-normorphinans and their pharmacological properties.
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.
Takeda
M
M
Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Inoue
H
H
Noguchi
K
K
Honma
Y
Y
Okamura
K
K
Date
T
T
Nurimoto
S
S
Yamamura
M
M
Saito
S
S
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D008253:Macaca mulatta; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000700:Analgesics; D009019:Morphinans