title: QSAR analysis of pyrazolidine-3,5-diones derivatives as Dyrk1A inhibitors.
abstract: Individuals with Down syndrome (DS) suffer from mental retardation. Overexpression and the resulting increased specific activity of Dyrk1A kinase located on chromosome 21 cause a learning and memory deficit in Dyrk1A transgenic mice. To search for therapeutic agents with Dyrk1A inhibition activity, previously we obtained HCD160 as a new hit compound for Dyrk1A inhibition. In the present study, we synthesized 34 HCD160 derivatives to investigate the quantitative structure-activity relationship (QSAR). This analysis could provide important information for novel drug discovery for treatment of DS related learning and memory deficits.
authors.affiliation: Biohealth Products Research Center, Inje University, Gimhae, Gyongnam, South Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Koo
authors.forename: Nam Doo
authors.initials: ND
authors.lastname: Kim
authors.forename: Yong Sog
authors.initials: YS
authors.lastname: Chon
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Jung
authors.forename: Burm-Jong
authors.initials: BJ
authors.lastname: Lee
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Woo-Joo
authors.initials: WJ
authors.lastname: Song
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D000097603:Dyrk Kinases
chemical_list: D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011720:Pyrazoles; D000097603:Dyrk Kinases; C443742:pyrazolidine-3,5-dione