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.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010047:Ovalbumin; D011738:Pyrilamine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005663:Furans; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D010047:Ovalbumin; D011738:Pyrilamine