Hexahydro-1H-1-pyrindines from acid rearrangement of 9-alkylidene-5-(m-methoxyphenyl)-2-methylmorphans. A new structural type of narcotic antagonists.

Awaya, H; May, E L; Aceto, M D; Harris, L S; Silverton, J V; Rice, K C; Mattson, M V; Jacobson, A E

Awaya, H; May, E L; Aceto, M D; Harris, L S; Silverton, J V; Rice, K C; Mattson, M V; Jacobson, A E.

J Med Chem ; 30(5): 947-50, 1987 May.

Article en En | MEDLINE | ID: mdl-3033248

RESUMEN

9-Methylene- and 9-ethylidene-5-(m-methoxyphenyl)-2-methylmorphans (1, 2) and refluxing 48% HBr have given rearrangement products 3 and 4, respectively. The structure of 4 [4a-ethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H-1- pyrindine] was determined by X-ray crystallography and that of 3 [1,4a-dimethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H- pyrindine] follows from analogy and NMR data. Compounds 3 and 4 are opioid antagonists of about the potency of nalorphine in the tail-flick vs. morphine assay and precipitate a complete abstinence syndrome in morphine-dependent monkeys. Both are nearly devoid of antinociceptive activity and they have about 0.025 times the affinity of nalorphine for the mu opioid receptor.

Asunto(s)

Alcaloides/farmacología; Antagonistas de Narcóticos; Piridinas; Alcaloides/metabolismo; Analgesia; Animales; Fenómenos Químicos; Química; Macaca mulatta; Masculino; Ratones; Morfina/antagonistas & inhibidores; Nalorfina/metabolismo; Nalorfina/farmacología; Naloxona/farmacología; Ratas; Ratas Endogámicas; Receptores Opioides/metabolismo; Receptores Opioides mu; Sodio/farmacología; Difracción de Rayos X

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridinas / Alcaloides / Antagonistas de Narcóticos Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 1987 Tipo del documento: Article Pais de publicación: Estados Unidos

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