Koo Kyung Ah, Kim Nam Doo, Chon Yong Sog, Jung Min-Su, Lee Burm-Jong, Kim Jung Ho, Song Woo-Joo
Biohealth Products Research Center, Inje University, Gimhae, Gyongnam, South Korea.
Bioorg Med Chem Lett. 2009 Apr 15;19(8):2324-8. doi: 10.1016/j.bmcl.2009.02.062. Epub 2009 Feb 21.
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.
唐氏综合征（DS）患者存在智力障碍。位于21号染色体上的Dyrk1A激酶的过表达及由此导致的比活性增加，会在Dyrk1A转基因小鼠中引起学习和记忆缺陷。为了寻找具有Dyrk1A抑制活性的治疗药物，我们之前获得了HCD160作为一种新的Dyrk1A抑制活性命中化合物。在本研究中，我们合成了34种HCD160衍生物，以研究定量构效关系（QSAR）。该分析可为治疗与DS相关的学习和记忆缺陷的新药研发提供重要信息。
