Synthesis, stereochemistry, and analgesic activity of 4-mono- and 4,4-disubstituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines

Autor:	Robert T. Parfitt, Abiodun O. Ogundaini
Rok vydání:	1985
Předmět:	Steric effects Analgesics Magnetic Resonance Spectroscopy Morphine Chemistry Stereochemistry Analgesic Antagonist Stereoisomerism Biological activity Carbon-13 NMR Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Cyclazocine Molecular Medicine Epimer Phenols
Zdroj:	Journal of Medicinal Chemistry. 28:177-181
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm00380a005
Popis:	The synthesis of 4-alkyl-, 4-aralkyl-, and 4-alkenyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines is described together with some 4,4-disubstituted and 8-hydroxy derivatives. Evidence of the stereochemistry of the 4-substituent was from 1H and 13C NMR. In the 4-methyl series the equatorial epimer 1b has a higher analgesic (hot-plate) potency than 1a, and 10a, 10c, and 10f are also good agonists. 5a afforded analgesic properties without an antagonist component. Surprisingly 10d, bearing an 8-OH function, was without analgesic activity, contrasting with the significant hot-plate activity exhibited by 1,2,3,4,5,6-hexahydro-3,5,6-trimethyl-2,6-methano-3-benzazocine. If the assumption is made that the more active enantiomorph in members of this series is configurationally related to (-)-morphine, then it may be that the enantiotopic edge in hexahydro-2,6-methano-3-benzazocines has a narrow steric requirement for analgesic responses.
Databáze:	OpenAIRE
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