QSAR analysis of pyrazolidine-3,5-diones derivatives as Dyrk1A inhibitors.
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.
Koo
Kyung Ah
KA
Biohealth Products Research Center, Inje University, Gimhae, Gyongnam, South Korea.
Kim
Nam Doo
ND
Chon
Yong Sog
YS
Jung
Min-Su
MS
Lee
Burm-Jong
BJ
Kim
Jung Ho
JH
Song
Woo-Joo
WJ
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
D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011720:Pyrazoles; D000097603:Dyrk Kinases; C443742:pyrazolidine-3,5-dione