Study On Synthesis And Anti-tumor Activity Of Chroman Derivatives With Triphenylethylene Scaffold

Estrogen is the key endogenous regulator to keep female physiologic equilibrium. If the level of estrogen is too high, the growth of breast cancer will be induced, if the level is too low, the physical disfunction such as osteoporosis will be resulted in.Tamoxifen is a typical estrogen receptor antagonist with triphenylethylene scaffold, which is widely used in the treatment of estrogen-dependent breast cancer. However the long-term use of tamoxifen suffers from serious limitations because of its adverse effects. An effective estrogen receptor antagonist should be found urgently.To discover an estrogen receptor antagonist with tissue selectivity, a new type of chroman derivatives with triphenylethylene scaffold has been designed and synthesized based on tamoxifen as the lead compound, and the anti-tumor activity will be evaluated.Seventeen chroman derivatives with triphenylethylene scaffold have been synthesized by condensation reaction, catalytic hydrogenation, McMurry reaction and etherification. All of the target compounds were characterized by IR, ~1H-NMR and ESI-MS, whereas fifteen of them were not reported in literature based on the search by SciFinder and other database.The antiestrogen activity of the target compounds is under study. Anti-tumor activity with the inhibition of the growth of human leukemic HL-60 cells exhibited in all tested four target compounds, i.e.7-[2-(diethylamino)ethoxy]-4-diphenylmethylenechroman(TPE-1), 4-diphenylmethyl ene-7-[2-(4-morpholinyl)ethoxy]chroman(TPE-2),4-diphenylmethylene-7-[2-(1-piperidinyl)ethoxy] chroman(TPE-3), 4-diphenylmethylene-6-[2-(4-morpholinyl)ethoxy]chroman (TPE-6).