RESUMO
A series of eight thienyloxymethylmorpholines, thiophene analogues of viloxazine, have been synthesized by three different routes. The preliminary pharmacological evaluation of this series shows antidepressant properties on the mice models used with a light sedative action. The structure-activity relationship is established in a first approximation.
Assuntos
Antidepressivos/síntese química , Antidepressivos/farmacologia , Viloxazina/análogos & derivados , 5-Hidroxitriptofano/farmacologia , Animais , Apomorfina/toxicidade , Blefaroptose/induzido quimicamente , Blefaroptose/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Hipotermia/induzido quimicamente , Hipotermia/tratamento farmacológico , Imipramina/farmacologia , Dose Letal Mediana , Masculino , Camundongos , Transtornos dos Movimentos/tratamento farmacológico , Pentobarbital/farmacologia , Sono/efeitos dos fármacos , Relação Estrutura-Atividade , Tetrabenazina/toxicidadeRESUMO
The synthesis of new 1-tert-butylamino-3-(3-thienyloxy)-2-propanols by two alternative methods is described. Their initial antiplatelet activity evaluation against ADP, adrenaline, and collagen is reported, and the preliminary structure-activity relationships are established. The appropriateness of further pharmacological investigations, especially for the best compound of the series 1f, is indicated.
Assuntos
1-Propanol/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Propanóis , 1-Propanol/síntese química , Adulto , Humanos , Masculino , Agregação Plaquetária/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Two series of compounds, structurally related to clozapine (CAS 5786-21-0), were tested for their neuroleptic activity. The derivatives 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzoxazepine and 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine at high doses were not cataleptogenic and only very weakly antagonized the amphetamine-or apomorphine-induced stereotyped behaviour in the rat, whereas at low doses they antagonized the amphetamine-induced hypermotility in mice. Thus these compounds might be efficient neuroleptics with little propensity to cause extrapyramidal side effects. On the other hand, the unsubstituted compound 10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine appeared to be an efficient neuroleptic agent with a greater propensity to cause these side effects.
Assuntos
Antipsicóticos/síntese química , Oxazepinas/síntese química , Piperazinas/síntese química , Tiazepinas/síntese química , Animais , Antipsicóticos/farmacologia , Antipsicóticos/toxicidade , Temperatura Corporal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Dextroanfetamina/farmacologia , Dopaminérgicos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Dose Letal Mediana , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Relaxantes Musculares Centrais/síntese química , Relaxantes Musculares Centrais/farmacologia , Oxazepinas/farmacologia , Oxazepinas/toxicidade , Piperazinas/farmacologia , Piperazinas/toxicidade , Ratos , Ratos Sprague-Dawley , Comportamento Estereotipado/efeitos dos fármacos , Tiazepinas/farmacologia , Tiazepinas/toxicidadeRESUMO
The syntheses of the thiophenic analogue of Moprolol (1d) and of its related compound 1a are described. From a preliminary pharmacological evaluation compound 1d seems worthy of further studies due to its notable beta-blocking activity and its remarkable anti-platelet aggregation action.
Assuntos
Antagonistas Adrenérgicos beta/síntese química , Propanolaminas/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/toxicidade , Animais , Hemodinâmica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Fenoxipropanolaminas , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Tiofenos/síntese química , Tiofenos/farmacologia , Tiofenos/toxicidadeRESUMO
The syntheses of the three possible thiophene analogs of lotucaine, and of other structurally related derivatives, are described. Preliminary data on their local anesthetic as well as antiplatelet aggregation activities are given.
Assuntos
Anestésicos Locais/síntese química , Pirrolidinas/síntese química , Anestésicos Locais/farmacologia , Anestésicos Locais/toxicidade , Animais , Fenômenos Químicos , Química , Humanos , Técnicas In Vitro , Dose Letal Mediana , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Pirrolidinas/farmacologia , Pirrolidinas/toxicidade , RatosRESUMO
The antiplatelet activity of twenty new thiophenic derivatives, grouped in three series, was studied according to the in vitro Born method. The DI50 for the three inducers of platelet aggregation ADP, adrenaline and collagen were calculated. The strong antiplatelet activity found in some of the compounds studied, which is even superior to that of the four classic antiplatelet drugs used is worth mentioning. The structure-activity relationships is discussed.
