3-methyl-1-(1-methyl-1H-pyrazol-3-yl)-1H-pyrrole-2,5-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-methyl-1-(1-methyl-1H-pyrazol-3-yl)-1H-pyrrole-2,5-dione
• 英文别名: 3-methyl-1-(1-methylpyrazol-3-yl)pyrrole-2,5-dione
• 化学式: C₉H₉N₃O₂
• 分子量: 191.19
• InChiKey: UPWIXROBQHXMSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.2
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• Methods and pharmaceutical compositions for the treatment of systemic mastocytosis
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)

  公开号：US11065230B2

  公开（公告）日：2021-07-20

  The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA Δ 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

  本发明涉及治疗系统性肥大细胞增多症的方法和药物组合物。本发明者展示了 KPT-251 处理对无 KIT 突变的 SCF 依赖性人肥大细胞（MC）系（WT ROSA）和两种 KIT 突变的因子依赖性 MC 系的影响：ROSA Δ 417-419 insY 和 ROSA D816V。KPT 是一种核输出选择性抑制剂（SINE），能特异性抑制输出蛋白-1（XPO1）的活性。KPT-251 在体外和体内对非癌造血细胞的毒性都很小。特别是，本发明涉及一种治疗有需要的全身性肥大细胞增多症患者的方法，包括向患者施用治疗有效量的 XPO1 抑制剂。
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF BETA-THALASSEMIAS
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3074007A1

  公开（公告）日：2016-10-05
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF SYSTEMIC MASTOCYTOSIS
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3512515A1

  公开（公告）日：2019-07-24
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US20170100378A1

  公开（公告）日：2017-04-13

  The present invention provides methods and pharmaceutical compositions designed to intervene in this defective process and to promote or restore erythrocyte maturation in individuals suffering from a myelodysplastic syndrome. The methods involve maintaining the activity of GATA-1 by preventing sequestration of Hsp70 in the cytoplasm. Accordingly, it is an object of this invention to provide methods of restoring or increasing erythrocyte maturation in a subject suffering from a myelodysplastic syndrome by preventing proteolytic inactivation of GATA-1. In some embodiments, preventing is achieved by administering to the subject a compound that inhibits the XPO1 nuclear transporter.
• US9675590B2
  申请人：——

  公开号：US9675590B2

  公开（公告）日：2017-06-13