RESUMO
Syntheses for 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone sodium salt monohydrate (9; MDL 427) and the related formamido compound, 2-(formylamino)-N-1H-tetrazol-5-ylbenzamide (10), are described. Both compounds are active in the rat passive cutaneous anaphylaxis and passive peritoneal anaphylaxis tests. A 94:6 equilibrium mixture of 9 and ionized 10, respectively, forms in aqueous buffer systems at a pH-dependent rate. In addition, analogues of 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone (8) bearing substituents on the benzene ring, substituents at the 2-position, and heteroaryl groups at the 3-position other than tetrazole were prepared. These analogue sets demonstrated that an accessible electrophilic center and an acidic functionality were requirements for good antiallergic activity.
Assuntos
Azóis/síntese química , Antagonistas dos Receptores Histamínicos H1/síntese química , Hipersensibilidade/tratamento farmacológico , Quinazolinas/síntese química , Tetrazóis/síntese química , Animais , Antagonistas dos Receptores Histamínicos H1/farmacologia , Liberação de Histamina/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Masculino , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Quinazolinas/farmacologia , Quinazolinonas , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Tetrazóis/farmacologiaRESUMO
This randomized, prospective study evaluates drainage of the subhepatic space in patients undergoing simple, uncomplicated cholecystectomy. One hundred twenty-two patients were divided into open (Penrose) drainage, closed sump drainage and no drainage groups. Open drainage resulted in increased morbidity and a longer postoperative hospital stay. The best results were in patients without drains. Subhepatic drainage is unnecessary in simple, uncomplicated cholecystectomy.