2-Benzyl-1,4-dioxane-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: 2-Benzyl-1,4-dioxane-2-carboxamide
• 英文别名: 2-benzyl-1,4-dioxane-2-carboxamide
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.25
• InChiKey: HMDYGIQVWUVVIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• [EN] BIDENTATE-BINDING MODULATORS OF LRRK2 AND JNK KINASES<br/>[FR] MODULATEURS DES LIAISONS BIDENTÉES DES KINASES LRRK2 ET JNK
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2014200682A1

  公开（公告）日：2014-12-18

  Both JNK and LRRK2 are associated with Parkinson's disease (PD), myocardial infarction (Ml), and other medical disorders. Here we report a reasonably selective and potent kinase inhibitors (e.g., compounds 6 and 10) that bound to both JNK and LRRK2 (a dual inhibitor). A bidentate-binding strategy that simultaneously utilized the ATP hinge binding and a unique protein surface site outside of the ATP pocket was applied to the design and identification of this kind of inhibitor. Compound 6 was a potent JNK3 and modest LRRK2 dual inhibitor with an enzyme IC50 value of 12 nM and 99 nM (LRRK2-G2019S), respectively. 6 also exhibited good cell potency, inhibited LRRK2:G2019S induced mitochondrial dysfunction in SHSY5Y cells, and was demonstrated to be reasonably selective against a panel of 116 kinases from representative kinase families.

  JNK和LRRK2都与帕金森病（PD）、心肌梗死（MI）和其他医学疾病相关联。在这里，我们报告了一种相对选择性和有效的激酶抑制剂（例如，化合物6和10），它们结合了JNK和LRRK2（双重抑制剂）。采用一种双齿结合策略，同时利用ATP铰链结合和ATP口袋外的独特蛋白表面位点，用于设计和识别这种抑制剂。化合物6是一种强效的JNK3和适度的LRRK2双重抑制剂，酶IC50值分别为12 nM和99 nM（LRRK2-G2019S）。6还表现出良好的细胞效力，在SHSY5Y细胞中抑制了LRRK2：G2019S诱导的线粒体功能障碍，并被证明对来自代表性激酶家族的116种激酶面板具有相当的选择性。
• BIDENTATE-BINDING MODULATORS OF LRRK2 AND JNK KINASES
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20160185818A1

  公开（公告）日：2016-06-30

  Both JNK and LRRK2 are associated with Parkinson's disease (PD), myocardial infarction (MI), and other medical disorders. Here we report a reasonably selective and potent kinase inhibitors (e.g., compounds 6 and 10) that bound to both JNK and LRRK2 (a dual inhibitor). A bidentate-binding strategy that simultaneously utilized the ATP hinge binding and a unique protein surface site outside of the ATP pocket was applied to the design and identification of this kind of inhibitor. Compound 6 was a potent JNK3 and modest LRRK2 dual inhibitor with an enzyme IC50 value of 12 nM and 99 nM (LRRK2-G2019S), respectively. 6 also exhibited good cell potency, inhibited LRRK2:G2019S induced mitochondrial dysfunction in SHSY5Y cells, and was demonstrated to be reasonably selective against a panel of 116 kinases from representative kinase families.

  JNK和LRRK2都与帕金森病（PD）、心肌梗死（MI）和其他医学疾病有关。在这里，我们报告了一种相对选择性和有效的激酶抑制剂（例如化合物6和10），它们结合了JNK和LRRK2（双重抑制剂）。采用一种双齿配体结合策略，同时利用ATP铰链结合和ATP口袋外的独特蛋白表面位点，设计和鉴定了这种抑制剂。化合物6是一种强效的JNK3和适度的LRRK2双重抑制剂，其酶IC50值分别为12 nM和99 nM（LRRK2-G2019S）。6还表现出良好的细胞效力，在SHSY5Y细胞中抑制了LRRK2：G2019S诱导的线粒体功能障碍，并被证明在代表性激酶家族的116个激酶面板中相对选择性较好。
• US9850276B2
  申请人：——

  公开号：US9850276B2

  公开（公告）日：2017-12-26