RESUMO
The reactions of morphine and its derivatives with phenyliodo(III)diacetate (PIDA) have been studied. This methodology has not been introduced to morphine alkaloids, despite the fact that such a strategy would ensure dearomatization of the electrophilic aromatic ring of morphine derivatives leading to nucleophilic ortho-quinoidal structures with potential pharmacological interest. The products, formed in regio- and diastereoselective or diastereospecific reactions, carry mixed-acetal or 1,3-dioxolane moieties. At low concentrations 6a has mu-opioid agonist character but in higher concentrations showed a non receptorial antagonist effect on isolated mouse vas deferens.
Assuntos
Acetatos/química , Analgésicos Opioides/síntese química , Analgésicos Opioides/farmacologia , Iodobenzenos/química , Derivados da Morfina/síntese química , Derivados da Morfina/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Cobaias , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Nociceptores/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/fisiologiaRESUMO
The development of beta-D-galactofuranosidase inhibitors provides a good chemotherapeutic target for treatment of major human diseases, because beta-D-galactofuranose is a constituent of important pathogen microorganisms but is absent in mammals. With this purpose we have prepared beta-D-galactofuranosyl nucleoside analogues, derived by the addition of nucleophiles to perbenzoylated beta-D-galactofuranosyl isothiocyanate, a compound previously prepared in this laboratory. N-beta-D-Galactofuranosyl-O-ethylthiourethane, N-beta-D-galactofuranosyl-4-oxoimidazolidine-2-thione, N-beta-D-galactofuranosyl-4-imidazoline-2-thione, and N-beta-D-galactofuranosyl-4-methoxyimidazolidine-2-thione, were prepared. The biological assays showed that imidazoline and imidazolidine-2-thione derivatives act as a new type of exo beta-D-galactofuranosidase inhibitor.
Assuntos
Galactosídeos/síntese química , Nucleosídeos/síntese química , beta-Galactosidase/antagonistas & inibidores , Galactosídeos/farmacologia , Humanos , Estrutura Molecular , Nucleosídeos/farmacologia , Penicillium/química , Penicillium/enzimologia , Tioglicosídeos/química , beta-Galactosidase/metabolismoRESUMO
From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery. Another group of 50 patients, who matched in risk factors and stage of disease, were treated with preoperative chemotherapy and surgery. Chemotherapy consisted of bleomycin, vincristine, mitolactol and methotrexate. All patients received 3 courses. Surgery was performed 2-3 weeks post-chemotherapy or 4-6 weeks postradiotherapy. Forty-four percent of the patients in the radiotherapy group showed recurrences, while 30% of the patients had recurrence in the chemotherapy group. The overall 3-year survival rate was 66% in the chemotherapy group and 57% in the radiation therapy group, with no statistical difference.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Mitolactol/administração & dosagem , Neoplasias Bucais/cirurgia , Cuidados Pré-Operatórios , Vincristina/administração & dosagemRESUMO
Results of the combined (irradiation + surgical) treatment of 33 patients, in great majority with advanced mouth cavity flattened epithelium are reported on. With 45% of the patients a 3 years survival could be obtained. The mainly radical surgical interventions were carried out after big dose preoperative irradiation treatment (Co. 60).