Assuntos
Migração de Corpo Estranho/cirurgia , Hematoma Epidural Espinal/etiologia , Estimulação da Medula Espinal/instrumentação , Lesões nas Costas/cirurgia , Lesões nas Costas/terapia , Eletrodos Implantados/efeitos adversos , Migração de Corpo Estranho/diagnóstico , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Estimulação da Medula Espinal/efeitos adversosRESUMO
The syntheses of the ring and four side-chain dihydroretinoic acids and/or their esters, 3-7, are described. The syntheses of several other retinoids containing a substituted aromatic ring are also included. The biological activity of the compounds was evaluated in vivo in a chemically induced mouse skin papilloma test and in vitro in two vitamin A deficient assays. The activity observed for 1a, 1c, and 2a in the former test was partially retained in the dihydro derivatives 4b, 4c, and 6b. Similar results were found in the in vitro assays.
Assuntos
Tretinoína/análogos & derivados , Vitamina A/análogos & derivados , Animais , Células Cultivadas , Cricetinae , Feminino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Técnicas de Cultura de Órgãos , Papiloma/tratamento farmacológico , RNA/metabolismo , Pele/citologia , Pele/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Tretinoína/síntese química , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Deficiência de Vitamina A/tratamento farmacológicoRESUMO
A series of compounds in which the 4-acetyl-3-hydroxy-2-propylphenoxy moiety of the standard SRS-A antagonist, FPL-55712, is linked by a polymethylene or a polyether chain to substituted (aryloxy)alkanoic acids was prepared. The compounds were evaluated for their ability to antagonize SRS-A-induced contractions of guinea pig ilea and LTE-induced bronchoconstriction in the guinea pig. The results showed that the compounds were all less potent than FPL-55712 in vitro, yet surprisingly, most were more potent by the inhalation route of administration. Some of the most potent analogues were selected for further pharmacological evaluation and, by inhalation, exhibited selective antagonism of leukotrienes as compared with PAF or histamine. In comparison to FPL-55712, compounds 28 and 37 were more potent against LTE (40- and 80-fold, respectively), LTD (4- and 3-fold, respectively), and LTC (27- and 20-fold, respectively) induced bronchoconstriction when tested by inhalation.
Assuntos
Ácidos Graxos/síntese química , Contração Muscular/efeitos dos fármacos , Éteres Fenílicos/síntese química , SRS-A/antagonistas & inibidores , Animais , Brônquios/efeitos dos fármacos , Brônquios/fisiologia , Ácidos Graxos/farmacologia , Cobaias , Técnicas In Vitro , Indicadores e Reagentes , Leucotrieno E4 , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Éteres Fenílicos/farmacologia , SRS-A/análogos & derivados , SRS-A/farmacologia , Espectrofotometria , Relação Estrutura-AtividadeRESUMO
(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo in a chemically induced mouse papilloma test; the toxicities were assessed in an in vivo mouse hypervitaminosis A test. Antipapilloma activity greater than the parent nonfluorinated ester was found for 1c (ethyl 12-fluororetinoate) and 23 and 39 (aromatic 4- and 6-fluororetinoid esters, respectively). A similar increase in antipapilloma activity was observed for 71 and 72, the aromatic 4- and 6-fluororetinoic acids, respectively, relative to 2 and for 73 (aromatic 4-fluororetinoid amide) relative to 4.