3-SUBSTITUTED 2-PHENYLINDOLES - SYNTHESIS AND BIOLOGICAL PROPERTIES

Knoevenagel-reaction of indol-3-carbaldehydes 5a,b and 7a,b with nitro methane leads to the nitroethenes 12 and 14, the analogous reaction wi th malodinitrile to the methylidenemalonic acid dinitriles 16.- Michae l-addition of nitromethane at 12 and 14 affords the 1,3-dinitropropane s 13 and 15, reduction of 16 the methylmalonic acid dinitriles 17.- Re action of indoles 3 with n-BuLi/phenylsulfonylchloride leads to the 3- chloroindoles 18, reaction with NaH/ethyliodide, ether cleavage and ac ylation to derivatives 19.- Compounds 7-11, 14-17, and 19 show affinit y to the estrogen receptor. Compounds 7b, 9-11, 17b, and 19b inhibit t he growth of MCF-7-and MDA-MB-231-cells. IC50-values are determined an d structure-activity relationships are discussed.