title: Synthesis and evaluation of aminopyridine derivatives as potential BACE1 inhibitors.
abstract: To identify a new non-peptidyl BACE1 inhibitor, we focused on the aminopyridine structure, which binds to the active sites of BACE1. Synthesis of aminopyridine derivatives and evaluation of inhibitory activity against rBACE1 are described. The 2-aminopyridine moiety and/or 3-methoxybenzaldehyde could be converted to terminal acetylene derivatives by the Sonogashira method. Sonogashira or Glaser cross-coupling reactions with the corresponding derivatives followed by hydrogenation could derive the designed compounds. Although inhibitory activities of the synthetic compounds against rBACE1 were weak, the aminopyridine motif has potential as a BACE1 inhibitor.
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: konno@yz.yamagata-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Taki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Iori
authors.initials: I
authors.lastname: Sakamoto
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D062105:Molecular Docking Simulation; D051381:Rats
chemical_list: D000631:Aminopyridines; D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Alzheimer’s disease; Amino pyridine; BACE1 inhibitor; Glaser coupling; Sonogashira coupling