Synthesis and biological evaluation of 3,4-diphenyl-1,2-dihydroisoquinolines as a new tamoxifen analogue.

3,4-Diphenyl-1,2-dihydroisoquinoline derivatives (1) as a new tamoxifen analogue were synthesized with trifluoromethanesulfonic acid from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (2), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 1 and 2, and 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolines (3) prepared by NaBH4 reduction of 1 against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. 1,2-Dihydroisoquinoline (1a) was the most active against MCF-7 cells in the compounds tested and the activity [IC50(micrograms/mL) 0.94] was nearly equipotent to that of tamoxifen. The structure-activity relationships of the compounds 1,2 and 3 were discussed.