3,5-Bis(arylidene)-4-piperidinones modified with bisphosphonate groups using a 1,2,3-triazole ring: Synthesis and antitumor properties

作者：Makarov M V^*; Rybalkina E Yu; Klemenkova Z S; Roeschenthaler G V

来源：Russian Chemical Bulletin, 2014, 63(10): 2388-2394.

DOI：10.1007/s11172-014-0752-y

• 3,5-bis(arylidene)-4-piperidinones
• bisphosphonates
• aminobisphosphonates
• 1,2,3-triazoles
• antitumor activity

An approach to the synthesis of new conjugates of 3,5-bis(arylidene)-4-piperidone pharmacophore with bisphosphonate moiety using a 1,2,3-triazole ring as a linker has been developed. The approach is based on a Cu(I)-catalyzed reaction of tetraethyl (but-3-yne-1,1-diyl)bisphosphonate with an alkyl azide containing a 3,5-bis(arylidene)-4-piperidone moiety. In vitro evaluation of antitumor activity of new conjugates 7a-d against human cancer cell lines HCT116 and MCF7 and human embryonic fibroblasts (HEF) has revealed that only compounds bearing strong electron-withdrawing substituents (cyano and nitro groups) in the aromatic rings possess moderate antitumor properties with the IC50 values ranging from 5 to 7.5 mu mol L-1.

• 出版日期2014-10