RESUMO
Omega-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)butyric, -hexanoic, and -octanoic acids were evaluated in the carrageenan paw edema assay. The most active compound, the butyric acid analogue, was 1.80 times more potent than the hexanoic compound, 1.15 times more potent than the octanoic analogue, and 0.43 times as potent as indomethacin.
Assuntos
Anti-Inflamatórios/síntese química , Dibenzoxepinas/síntese química , Animais , Anti-Inflamatórios/uso terapêutico , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/uso terapêutico , Dibenzoxepinas/uso terapêutico , Edema/tratamento farmacológico , Ratos , Relação Estrutura-AtividadeRESUMO
HP 549 is an orally effective non-steroidal anti-inflammatory agent with moderate analgesic and antipyretic activity. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. HP 549 also inhibits carrageenan-induced paw edema in the rat, an activity which is not altered by adrenalectomy. The analgesic activity of HP 549 was demonstrated in phenylquinone writhing. However, HP 549 produced variable results in the Randall-Selitto analgesia test. The anti-pyretic activity of HP 549 appears to be weak. HP 549, unlike other pharmacologically active anti-inflammatory drugs, does not produce gastric irritation at effective doses and is 45 times less ulcerogenic than indomethacin. Also the acute therapeutic indices for HP 549 are more favorable than for indomethacin.
Assuntos
Anti-Inflamatórios/farmacologia , Dibenzoxepinas/farmacologia , Acetatos , Analgésicos , Animais , Anti-Inflamatórios/toxicidade , Artrite Experimental/fisiopatologia , Dibenzoxepinas/toxicidade , Edema/fisiopatologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Granuloma/fisiopatologia , Indometacina/farmacologia , Irritantes , Dose Letal Mediana , Masculino , Camundongos , Coelhos , Ratos , Tempo de Reação/efeitos dos fármacosRESUMO
4,10-Dihydro-10-oxofuro[3,2-c][1]benzoxepin-8-acetic acid and 4,10-dihydro-10-oxothieno[3,2-c][1]benzoxepin-8-acetic acid were evaluated in the carrageenan paw edema assay with the thieno analogue being ten times more active than the furano compound and 1.3. times more active than indomethacin. The therapeutic ratio (antiinflammatory activity/gastric irritation liability) of the thieno analogue was 25 times that of indomethacin.
Assuntos
Anti-Inflamatórios/síntese química , Benzoxepinas/síntese química , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Benzoxepinas/efeitos adversos , Benzoxepinas/uso terapêutico , Edema/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Métodos , Ratos , Relação Estrutura-AtividadeRESUMO
A series of 6,11-dihydrodibenz[b,e]oxepin-2-acetic acids has been evaluated for both antiinflammatory and analgetic activity in the carrageenan paw edema and phenylquinone writhing assays. The requirements for optimal activity in this series appear rather specific: (a) an unsubstituted 6,11-dihydrodibenz[b,e]oxepin nucleus and (b) a carbonyl group in the 11 position. One derivative, 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid (11), has been selected for further study.
