RESUMO
A series of substituted 1,3-diaryltriazenes has been synthesized and tested for anorectic activity. Several members of the series were effective; one compound, 1,3-bis[2-cyano-5-(trifluoromethyl)phenyl]triazene, was particularly active, causing weight loss in rats, dogs, and squirrel monkeys. It was devoid of overt central nervous system activity, and compared to previously reported biologically active triazenes, it was relatively nontoxic up to 30 days of drug administration.
Assuntos
Depressores do Apetite , Triazenos/síntese química , Animais , Depressores do Apetite/síntese química , Peso Corporal/efeitos dos fármacos , Dextroanfetamina/farmacologia , Cães , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Ingestão de Alimentos/efeitos dos fármacos , Fenfluramina/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos , Saimiri , Relação Estrutura-Atividade , Triazenos/farmacologiaRESUMO
One hundred and seven 4-quinolinehydrazones were synthesized and tested in vivo against the tapeworm Hymenolepis nana. Twenty-five derivatives showed significant cestocidal activity; structure-activity correlations were performed using Free-Wilson methodology. Two compounds, 2,6-dimethyl-4-[(3-pyridinylmethylene)hydrazino]quinoline and 2,6-dimethyl-4-[2p][(6-methyl)pyridinylmethylene]hydrazino)quinoline, predicted to be maximally active, effected 100% reduction of H. nana in mice at 200 mg/kg, p.o.
Assuntos
Anticestoides , Hidrazonas/uso terapêutico , Himenolepíase/tratamento farmacológico , Quinolinas/uso terapêutico , Animais , Anticestoides/uso terapêutico , Hidrazonas/farmacologia , Hymenolepis/efeitos dos fármacos , Masculino , Camundongos , Quinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
In the search for prostaglandin-like structures capable of exerting specific and desirable biological properties, a variety of simple heterocyclic homoprostanoidal derivatives was synthesized from readily available stearic acid derivatives. Compounds 5b and 5e were found to be more than 100 times as potent as PGE1 and PGE2 in a tracheal chain bioassay and, like 6, 9, and 12, inhibited PGE2-induced diarrhea. Derivatives 6 and 7a showed significant PG-synthetase inhibitor activity.
Assuntos
Prostaglandinas/síntese química , Animais , Gatos , Depressão Química , Diarreia/induzido quimicamente , Dioxóis/síntese química , Dioxóis/farmacologia , Cobaias , Técnicas In Vitro , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Prostaglandinas/biossíntese , Prostaglandinas/farmacologia , Prostaglandinas E/antagonistas & inibidores , Ratos , Sulfetos/síntese química , Sulfetos/farmacologia , Tionas/síntese química , Tionas/farmacologia , Traqueia/efeitos dos fármacosRESUMO
A group of tricyclic analogs of flufenamic acid were tested for their ability to inhibit both the biosynthesis of prostaglandin and carrageenan-induced inflammation of the rat paw. All had activity greater than phenylbutazone as inhibitors of prostaglandin synthetase, with SK&F 22908 being as active as flufenamic acid. The anti-inflammatory activities of these compounds correlated only to a minor degree with the inhibition of prostaglandin biosynthesis. The data support the position that within this series of compounds inhibition of prostaglandin synthetase and non-steroidal antiinflammatory activity, as well as ulcerogenic liability, may be an expression of different mechanisms.
Assuntos
Anti-Inflamatórios/farmacologia , Carragenina/antagonistas & inibidores , Inibidores de Ciclo-Oxigenase , Edema/tratamento farmacológico , Ácido Flufenâmico/análogos & derivados , Oxigenases de Função Mista/antagonistas & inibidores , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/farmacologia , Bovinos , Edema/induzido quimicamente , Ácido Flufenâmico/farmacologia , Ácido Flufenâmico/uso terapêutico , Técnicas In Vitro , Masculino , Microssomos/enzimologia , Ratos , Glândulas Seminais/ultraestrutura , Relação Estrutura-AtividadeRESUMO
Eighty-four 4-quinolinehydrazones were synthesized and tested for antiviral activity. Thirty nine derivatives were active against influenza A2 and/or Coxsackie B1 in mice at a dose of 25 mg/kg sc. Structure-activity relationships of 44 derivatives (21 inactive) were analyzed qualitatively using a modified Free-Wilson approach.
Assuntos
Antivirais/síntese química , Quinolinas/síntese química , Animais , Antivirais/uso terapêutico , Infecções por Coxsackievirus/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Hidrazonas/síntese química , Hidrazonas/uso terapêutico , Cinética , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Quinolinas/uso terapêutico , Relação Estrutura-AtividadeAssuntos
Anti-Inflamatórios/farmacologia , Ouro/farmacologia , Leishmaniose/tratamento farmacológico , Mycoplasma/efeitos dos fármacos , Administração Oral , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Aurotioglucose/farmacologia , Aurotioglucose/uso terapêutico , Cricetinae , Ouro/uso terapêutico , Tiomalato Sódico de Ouro/farmacologia , Tiomalato Sódico de Ouro/uso terapêutico , Masculino , Camundongos , Fosfinas/farmacologia , Fosfinas/uso terapêuticoAssuntos
Hipoglicemiantes/síntese química , Ácidos Picolínicos/síntese química , Administração Oral , Animais , Glicemia/análise , Depressão Química , Diabetes Mellitus Experimental/metabolismo , Gluconeogênese/efeitos dos fármacos , Cobaias , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Injeções Intraperitoneais , Córtex Renal/efeitos dos fármacos , Glicogênio Hepático/metabolismo , Masculino , Camundongos , Ácidos Picolínicos/administração & dosagem , Ácidos Picolínicos/farmacologia , Ratos , Relação Estrutura-Atividade , Compostos de Sulfidrila/administração & dosagem , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/farmacologiaRESUMO
1. 3-Mercaptopicolinic acid (SK&F 34288) inhibited gluconeogenesis in vitro, with lactate as substrate, in rat kidney-cortex and liver slices. 2. In perfused rat livers, gluconeogenesis was inhibited when lactate, pyruvate or alanine served as substrate, but not with fructose, suggesting pyruvate carboxylase or phosphoenolpyruvate carboxylase as the site of inhibition. No significant effects were evident in O(2) consumption, hepatic glycogen, urea production, or [lactate]/[pyruvate] ratios. 3. A hypoglycaemic effect was evident in vivo in starved and alloxan-diabetic rats, starved guinea pigs and starved mice, but not in 4h-post-absorptive rats. 4. In the starved rat the hypoglycaemia was accompanied by an increase in blood lactate. 5. A trace dose of [(14)C]lactate in vivo was initially oxidized to a lesser extent in inhibitor-treated rats, but during 90min the total CO(2) evolved was slightly greater. The total amount of the tracer oxidized was not significantly different from that in the controls.