Synthesis and antiproliferative properties of N3/8-disubstituted 3,8-diazabicyclo[3.2.1]octane analogues of 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl-piperazine

Article abstract of DOI:10.1016/j.ejmech.2006.11.013

A series of novel N_3/8-disubstituted-3,8-diazabicyclo[3.2.1]octanes in order to improve the in vitro activity of the prototype 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridyl-4-yl)methylpiperazine (1) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines. Compounds 2a,b,f and m demonstrated not only growth-inhibitory activities against leukemia cancer cells, but also fairly good activities against the growth of certain solid tumors. Among them, 2a is the most potent one with IC₅₀ values in the low micromolar range. Moreover, compound 2a has been selected for in vitro testing on MCF-7 cell to evaluate the mode of action of this lead compound.