Synthesis of 3'-methoxy-E-diethylstilbestrol and its analogs as tumor angiogenesis inhibitors.

3'-Methoxy-E-diethylstilbestrol (2), with the structural and original similarities to 2-methoxyestradiol (2-ME2, 1), was synthesized and screened against HUVEC and a series of human cancer cell lines including RL95-2, SKOV-3, MCF-7 and T-47D in vitro. The configuration of the title compound was determined via the single crystal X-ray diffraction of its benzoyl-ester derivative (10). The fact that 3'-methoxy-E-diethylstilbestrol and its analogues (8 and 11) showed potential antiangiogenesis and anti-tumor activities at a close level, whereas its ester derivative (10) did not display any cytotoxic activities on all the screening cell lines indicated that the core scaffold of 3'-methoxy-3,4-diphenylhexane and the exposed hydroxyl-groups in the structures are essential pharmacophores for their anti-tumor activities. Copyright Â