Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to improve oral efficacy are discussed.
Brown, M. F., Marfat, A., Antognoli, G., Chambers, R. J., Cheng, J. B., Damon, D. B., … Watson, J. W. (1998). N-carbamoyl analogs of Zafirlukast: Potent receptor antagonists of leukotriene D4. Bioorganic and Medicinal Chemistry Letters, 8(18), 2451–2456. https://doi.org/10.1016/S0960-894X(98)00442-9