Crystal and molecular structure of nafoxidine and stereochemical features of anticancer antiestrogens

We have determined the molecular structure of the anticancer antiestrogen nafoxidine and compared its three-dimensional structure with two other clinically useful antiestrogens in order to delineate stereochemical parameters in these compounds. Crystals of nafoxidine hydrochloride-ethanol are monoclinic with cell dimensions a = 17.040, b = 7.967, c = 25.260 A, beta = 123.7 degrees, and space group P21/c with four formula units per cell. The structure was solved by direct phasing methods and refined to a discrepancy index of 0.068. The methoxyphenyl and phenyl rings are trans to each other relative to the ethylene bond, and the substituted amine-aryl ether chain has an extended conformation. Stereoscopic superposition drawings and tabular data are given to show structural similarities and difference in nafoxidine, clomiphene, and tamoxifen, the three antiestrogens with with demonstrated clinical efficacy in the management of metastatic mammary carcinoma.