Hexestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors

With the erythro-hexestrol derivative 2 as the starting material, a variety of cytotoxic linked hexestrol (HEX) compounds were prepared including the HEX-N-lost derivative 36, the HEX-(chloroethyl)nitrosourea 38, the HEX-cyclophosphamide 44, and the HEX-epoxide 68. Relative binding affinity to estradiol receptors were in the magnitude of 1%, similar to that of comparable diethylstilbestrol compounds. HEX derivatives with long polyether spacers (64, 65, 70, 71) showed no significant decrease in binding affinity in contrast to derivatives with other bulky side chains.