Synthesis and analgesic activity of some spiro[dibenz[b,f]oxepin-10,4'-piperidine] derivatives

A series of 10,11-dihydro-11-oxospiro[dibenz[b,f]oxepin-10,4'-piperdine] derivatives (II) was synthesized and evaluated for analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Preliminary structure-activity correlations indicate that optimum activity is...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1979-07, Vol.22 (7), p.834-839
Main Authors: Ong, Helen H, Profitt, James A, Spaulding, Theodore C, Wilker, Jeffrey C
Format: Article
Language:English
Subjects:
Analgesics - chemical synthesis
Animals
Dibenzoxepins - chemical synthesis
Dibenzoxepins - pharmacology
Dose-Response Relationship, Drug
Male
Methods
Mice
Postural Balance - drug effects
Quinones - antagonists & inhibitors
Reaction Time - drug effects
Spiro Compounds - chemical synthesis
Spiro Compounds - pharmacology
Structure-Activity Relationship
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Summary:A series of 10,11-dihydro-11-oxospiro[dibenz[b,f]oxepin-10,4'-piperdine] derivatives (II) was synthesized and evaluated for analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Preliminary structure-activity correlations indicate that optimum activity is associated with a short-chain (R less than or equal to C2) N substituent and a nuclear fluorine function, as exemplified by 9b. This compound, when administered orally, was equipotent to morphine in protecting against mouse writhing. The observation that the PQW activity of 9b remained relatively unchanged after naloxone challenge seems to favor a nonnarcotic profile.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00193a016