Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain

• DOI: 10.1016/j.ejmech.2015.04.055
• Publication Date: 2015-05-02T16:43:41Z
• Authors: Yaghoub Pourshojaei; Ali Gouranourimi; Shohre Hekmat; Ali Asadipour; Samira Rahmani-Ne...; Alireza Moradi; Hamid Nadri; Farshad Homayouni...; Saeed Emami; Alireza Foroumadi; Abbas Shafiee
• Keywords: Tacrine; Side chain; Residue (chemistry); Structure–activity relationship; Cholinesterase; Aromatic amine

A series of 3-(4-(aminoalkoxy)benzylidene)-chroman-4-ones 7a-r were designed and synthesized as analogs of homoisoflavonoids which are well known natural products with diverse pharmacological properties related to Alzheimer's disease. The in vitro anti-cholinesterase activity of designed compounds 7a-r against AChE and BuChE, revealed that compounds bearing piperidinylethoxy residue showed potent activity against AChE at sub-micromolar level (IC50 values = 0.122-0.207 μM), more potent than reference drug tacrine. The structure-activity relationships study of piperidinylethoxy series demonstrated that the selectivity and physicochemical properties of compounds could be optimized by selection of a proper substituent on the C-7 position of chroman ring, while the high potency of the molecule against AChE was reserved.