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.
Kihara
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Ikeuchi
M
M
Nagao
Y
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D007624:KB Cells / Q000187:drug effects; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007546:Isoquinolines; D013629:Tamoxifen