Stein P D, Floyd D M, Bisaha S, Dickey J, Girotra R N, Gougoutas J Z, Kozlowski M, Lee V G, Liu E C, Malley M F
Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
J Med Chem. 1995 Apr 14;38(8):1344-54. doi: 10.1021/jm00008a013.
Random screening of compounds in an ETA receptor binding assay led to the discovery of a class of benzenesulfonamide ligands. Optimization led to the development of 5-amino-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamides which were functional antagonists. Structural features which were important to activity included a 1,5-substitution pattern on the naphthalene ring; a sulfonamide NH with a pK value < 7; an amine, preferably with alkyl substituents, at the 5-position; and methyl groups on both the 3- and 4-positions of the isoxazole.
