Acidic furo[3,2-b]indoles. A new series of potent antiallergy agents

A series of furo[3,2-b]indole carboxylic acids, tetrazoles, and carbamoyltetrazoles was prepared and tested in vitro with use of a model of active pulmonary anaphylaxis, the modified Schultz-Dale Test (SDT). In this model, isolated guinea pig lung strips are repeatedly challenged with antigen in the presence of an antihistamine (H1). Most of the acidic furo[3,2-b]indoles tested inhibited the leukotriene-mediated lung contraction in a dose-related manner. Compounds with an N-phenyl substituent were more potent (IC50 less than or equal to 5.0 microM) inhibitors of SDT than the N-methyl analogues (IC50 greater than or equal to 22.0 microM). Most of the N-phenyl analogues were more potent in SDT than Fisons' mediator-release inhibitor proxicromil (FPL-57,787; IC50 = 6.3 microM). The most potent furo[3,2-b]indoles were those unsubstituted at C-7 and with N-phenyl, 2-carbamoyltetrazole, and 3-alkoxy substituents. All of the carboxylic acid ester analogues tested were weak or inactive at concentrations of 10-30 microM.