2-(2,6-difluorocyclohexa-2,4-dien-1-yl)-N-(4-pyrrolidin-3-yloxypyrimidin-5-yl)-1,3-thiazole-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2,6-difluorocyclohexa-2,4-dien-1-yl)-N-(4-pyrrolidin-3-yloxypyrimidin-5-yl)-1,3-thiazole-4-carboxamide
• 化学式: C₁₈H₁₇F₂N₅O₂S
• 分子量: 405.4
• InChiKey: SKOWPPALUFOEPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  9

文献信息

• PIM KINASE INHIBITOR AND PREPARATION METHOD AND USE IN MEDICINAL MANUFACTURE THEREOF
  申请人：Jikai Biosciences Inc.

  公开号：EP2743271A1

  公开（公告）日：2014-06-18

  The present invention provided a PIM kinase inhibitor - a compound with a general structural formula represented by Formula I. Also provided are isomers, diastereomers, enantiomers, tautomers, and pharmaceutically acceptable salts represented by Formula 1. E, J1, J2, Q, X, Y, Z and m in Formula I are defined in Claim 1. A PIM biochemical assay shows that the compounds (1-63) of the present invention can significant inhibit PIM-1 kinase activity. At 3 micromolar concentration, the compounds of the present invention can inhibit PIM-2 and PIM-3 activities by as much as 100%. Therefore, the PIM kinase inhibitors of the present invention can be used to prepare drugs to treat PIM kinase mediated diseases such as cancers, autoimmune diseases, allergic reactions, or organ transplant rejection, thus have great clinical value. Also provided are preparation methods for the compounds represented by Formula 1.

  本发明提供了一种PIM激酶抑制剂--通式结构式由式I代表的化合物。还提供了由式 1 表示的异构体、非对映异构体、对映体、同系物和药学上可接受的盐。式 I 中的 E、J1、J2、Q、X、Y、Z 和 m 在权利要求 1 中定义。PIM生化试验表明，本发明的化合物（1-63）能显著抑制PIM-1激酶的活性。在 3 微摩尔浓度下，本发明化合物对 PIM-2 和 PIM-3 活性的抑制率高达 100%。因此，本发明的 PIM 激酶抑制剂可用于制备治疗 PIM 激酶介导的疾病（如癌症、自身免疫性疾病、过敏反应或器官移植排异反应等）的药物，具有极大的临床价值。本发明还提供了式 1 所代表化合物的制备方法。
• PIM KINASE INHIBITORS AND PREPARATION METHOD AND USE IN MEDICINAL MANUFACTURE THEREOF
  申请人：Jikai Biosciences Inc.

  公开号：EP2743271B1

  公开（公告）日：2017-05-31