title: Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran 14176, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Pourshojaei
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran 14176, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Gouranourimi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran 14176, Iran.
authors.forename: Shohre
authors.initials: S
authors.lastname: Hekmat
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Asadipour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran 14176, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Rahmani-Nezhad
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Farshad Homayouni
authors.initials: FH
authors.lastname: Moghadam
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran; Drug Design and Development Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran 14176, Iran. Electronic address: ashafiee@ams.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008958:Models, Molecular
chemical_list: D000588:Amines; D001597:Benzylidene Compounds; D002800:Cholinesterase Inhibitors; D002867:Chromones
keywords: Acetylcholinesterase; Alzheimer's disease; Chroman-4-one; Docking study; Homoisoflavonoids