RESUMO
The synthesis of water soluble hydrochlorides of indazole derivatives 1b, 8 and 9 is described. By treating of 2,5-dinitroindazole with thiomorpholine 3-thiomorpholino-5-nitroindazole (10) and 3,5-dinitroindazole (11) in the form of the molecular compound 11a are obtained. The known indazole derivatives 1 and 7 as well as the newly synthesized hydrochlorides of 1b, 8 and 9 are, except of 8.HCl, less toxic than benzydamine hydrochloric (BZD). The same compounds show with some excepts a comparable or greater antiinflammatory effect than BZD in the carrageenin induced oedema test.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Indazóis/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Indazóis/farmacologia , Indazóis/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Ratos , Ratos WistarRESUMO
beta-(4-Pyrazole)acrylic acids 22-28 were prepared by the Knoevenagel reaction of malonic acid and 4-formylpyrazoles 8-14. 4-Pyrazolemethylenemalonic acids 15-21 were isolated as intermediates. The latter compounds were also synthesized by treating the 4-formylpyrazoles 8-14 with diethyl malonate followed by hydrolysis of the obtained diethyl esters 15a-21a. The effect of piperidine and pyridine on the Knoevenagel condensation was investigated. The beta-(4-pyrazole)acrylic acids 22-27, on catalytic reduction, gave the corresponding beta-(4-pyrazole)propionic acids 29-34. Compounds 23, 24, 27, 29-31 and 34 appeared to be less active than phenylbutazone in carrageenin-induced oedema test, but they were less toxic than the reference drug.
Assuntos
Acrilatos/síntese química , Anti-Inflamatórios/síntese química , Propionatos/síntese química , Pirazóis/síntese química , Acrilatos/farmacologia , Acrilatos/toxicidade , Animais , Fenômenos Químicos , Química , Masculino , Camundongos , Propionatos/farmacologia , Propionatos/toxicidade , Pirazóis/farmacologia , Pirazóis/toxicidade , Ratos , Ratos EndogâmicosRESUMO
Eight new 4-methylamino-2-phenylquinoline-3-carboxamides were obtained. Three of them were screened pharmacologically and all turned out to be antiinflammatory, analgesic and sedative compounds. Their properties were compared to those of indomethacin and pethidine.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Quinolinas/síntese química , Agressão/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Anticonvulsivantes , Fenômenos Químicos , Química , Hipnóticos e Sedativos , Dose Letal Mediana , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Parassimpatolíticos , Quinolinas/farmacologia , Quinolinas/toxicidade , Ratos , Ratos EndogâmicosRESUMO
Pirolo [3,4-e] [1,4]-diazepine derivatives: 5-(2'-naphtyl) (7-phenyl-) 2, 3, 6, 8-tetrahydro)-pirolo-[3,4-e] [1,4]-diazepine-6-thiox-8-(1H,7H)-one (PD) and 5-(2'-naphtyl) 7-p-chlorophenyl-(2, 3, 6, 8-tetrahydro)-pirolo-[3,4-e] [1,4]-diazepine-6-thiox-8-(1H, 7H)-one (PDC1) show distinct analgesic properties, but no marked antiinflammatory activity in vivo. In addition these compounds inhibit rat blood platelet aggregation in vivo, and produce contractions of the rat's pregnant uterus.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Azepinas/síntese química , Animais , Aspirina/farmacologia , Azepinas/farmacologia , Carragenina , Fenômenos Químicos , Química , Edema/induzido quimicamente , Feminino , Gossypium , Granuloma/induzido quimicamente , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Pleurisia/induzido quimicamente , Gravidez , Ratos , Ratos Endogâmicos , Tempo de Reação/efeitos dos fármacos , Terebintina , Contração Uterina/efeitos dos fármacosRESUMO
Morpholids, N-methylpiperazids, piperidids and pyrrolidids of 5-methyl, 3,5-dimethyl-1-phenyl-4-pyrazolthioacetic acid and 3,5-dimethyl-1-phenyl-4-pyrazolcarbonic acid 4-12 are obtained by the Willgerodt-Kindler procedure. The oxothioamids 13-19 result as the intermediate products of the synthesis of thioamids 4-10. The compounds 4, 5, 8, 9, 11, 14 and 17 do not respond to Mycobacterium tuberculosis H37Rv. The thioamids 4, 8 and 11 are of slight toxicity (LD50 greater than 2.8 g/kg, albino-Swiss mice) and inhibit the Carrageenin oedema of the Wistar rat claw minor than phyenylbutazon and indometacin.
Assuntos
Antituberculosos/síntese química , Pirazóis/síntese química , Animais , Anti-Inflamatórios/síntese química , Fenômenos Químicos , Química , Dose Letal Mediana , Masculino , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/toxicidade , Ratos , Ratos EndogâmicosAssuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Gota/tratamento farmacológico , Tiazinas/uso terapêutico , Animais , Anti-Inflamatórios/metabolismo , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Cinética , Piroxicam , Ratos , Tiazinas/metabolismoRESUMO
4-propionyl-4-(4-chlorophenyl)-1-(3-dimethylaminopropyl)-piperidine dihydro-chloride (S8) showed in the hot plate test a marked analgesic activity with a better therapeutic index than that of pethidine. S8 possesses also anti-inflammatory (in short and long-term tests in vivo) as well as spasmolytic properties.
Assuntos
Anti-Inflamatórios não Esteroides , Piperidinas/farmacologia , Animais , Estimulação Elétrica , Dose Letal Mediana , Masculino , Camundongos , Parassimpatolíticos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Participation of histamine in the inflammatory reaction produced by carrageenan was studied. Mepyramine did not influence the course of the inflammatory reaction. In contrast to when mepyramine was used, there was a significant inhibition of carrageenan oedema when cimetidine was used. Pretreatment of animals with compound 48/80 significantly reduced the oedema formation. Neither mepyramine nor cimetidine reversed the inhibition of rat paw swelling produced by histamine liberators. It is concluded that histamine participates in carrageenan oedema via its H2-receptors and that the anti-inflammatory effect of compound 48/80 is not connected with the 'anti-inflammatory' action of liberated histamine.
Assuntos
Edema/fisiopatologia , Histamina/fisiologia , Animais , Carragenina , Cimetidina/farmacologia , Edema/induzido quimicamente , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Masculino , Pletismografia , Pirilamina/farmacologia , Ratos , Ratos Endogâmicos , Fatores de Tempo , p-Metoxi-N-metilfenetilamina/farmacologiaAssuntos
Anti-Inflamatórios/uso terapêutico , Hidroxitolueno Butilado/análogos & derivados , Anticoagulantes , Hidroxitolueno Butilado/uso terapêutico , Epoprostenol/antagonistas & inibidores , Epoprostenol/biossíntese , Humanos , Fosfolipídeos/metabolismo , Agregação Plaquetária , Antagonistas de Prostaglandina , Prostaglandinas E/antagonistas & inibidores , Prostaglandinas E/biossíntese , Prostaglandinas F/antagonistas & inibidores , Prostaglandinas F/biossíntese , Tromboxano A2/antagonistas & inibidores , VasodilatadoresRESUMO
Substance 48/80 (condensation product of p-methoxy-N-methylphenethylamine with formaldehyde) is known to cause release of histamine and serotonin from the granules in mastocytes. The effect of this substance on the course of experimental inflammation was studied in rats. It was found that substance 48/80 produced local reactions (paw oedema, pleural exudate), while after systemic administration it exerted an antiexudative and antioedematous effect. It is suggested that local signs after administration of the substance are caused, probably, by histamine and serotonin release from the mastocytes and participation of these substances in the inflammatory reaction, since this reaction was partly blocked by antihistamine and antiserotonin agents. The mechanism of inhibition of the inflammatory reactions after systemic administration of the substance is discussed.
Assuntos
Angioedema/induzido quimicamente , Pleurisia/induzido quimicamente , p-Metoxi-N-metilfenetilamina/efeitos adversos , Animais , Liberação de Histamina/efeitos dos fármacos , Masculino , Mastócitos/metabolismo , Derrame Pleural/induzido quimicamente , Ratos , Serotonina/metabolismoAssuntos
Intestino Delgado/efeitos dos fármacos , Isoquinolinas/farmacologia , Músculo Liso/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Animais , Sinergismo Farmacológico , Feminino , Cobaias , Técnicas In Vitro , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Noscapina/farmacologia , Papaverina/farmacologiaRESUMO
The purpose of this work was to check the effect of 4-valeryl 4-(3--chlorophenyl) 1-[3-(4-methylpiperazine)-propyl]-piperidine, a new synthetic piperidine derivative, on the activity of smooth musculature of guinea pig isolated intestine. Direct and indirect myolytic action of this compound was found.