N-[(2-chloro-6-fluorophenyl)methyl]-1,3-dimethylpyrrole-2-carboxamide | 1041644-30-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[(2-chloro-6-fluorophenyl)methyl]-1,3-dimethylpyrrole-2-carboxamide
• CAS: 1041644-30-7
• 化学式: C₁₄H₁₄ClFN₂O
• 分子量: 280.729
• InChiKey: UHHDIHHKNGLHKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氯-6-氟苄胺 、 1,3-dimethyl-1H-pyrrole-2-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N-[(2-chloro-6-fluorophenyl)methyl]-1,3-dimethylpyrrole-2-carboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC INHIBITORS OF NECROPTOSIS
  [FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA NÉCROPTOSE

  摘要：

  该发明涉及一系列杂环衍生物，可以抑制肿瘤坏死因子α（TNF-α）诱导的坏死程序。该发明的杂环化合物由化学式（I）和（Ia）-（Ie）描述，并且已经证明可以抑制人类Jurkat T细胞中FADD缺陷变体中TNF-α诱导的坏死程序。该发明还涉及含有该发明化合物的药物组合物。该发明的化合物和组合物也可用于治疗坏死程序可能起重要作用的疾病。

  公开号：

  WO2009023272A1

文献信息

• [EN] HYBRID NECROPTOSIS INHIBITORS<br/>[FR] INHIBITEURS HYBRIDES DE LA NÉCROPTOSE
  申请人：HARVARD COLLEGE

  公开号：WO2014145022A1

  公开（公告）日：2014-09-18

  The present invention relates to heterocyclic compounds (e.g., compounds described by Formula (I)) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role. The heterocyclic compounds described herein can also achieve improved activity and selectivity towards RIP1 and/or RIP3.

  本发明涉及杂环化合物（例如，由式（I）描述的化合物）及其药学上可接受的盐。该发明还涉及包括这些化合物的药物组合物，以及它们在治疗可能出现大量坏死相关凋亡的疾病中的用途。本文描述的杂环化合物还可以实现对RIP1和/或RIP3的改进活性和选择性。
• [EN] HETEROCYCLIC INHIBITORS OF NECROPTOSIS<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA NÉCROPTOSE
  申请人：HARVARD COLLEGE

  公开号：WO2009023272A1

  公开（公告）日：2009-02-19

  The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

  该发明涉及一系列杂环衍生物，可以抑制肿瘤坏死因子α（TNF-α）诱导的坏死程序。该发明的杂环化合物由化学式（I）和（Ia）-（Ie）描述，并且已经证明可以抑制人类Jurkat T细胞中FADD缺陷变体中TNF-α诱导的坏死程序。该发明还涉及含有该发明化合物的药物组合物。该发明的化合物和组合物也可用于治疗坏死程序可能起重要作用的疾病。
• HETEROCYCLIC INHIBITORS OF NECROPTOSIS
  申请人：President and Fellows of Harvard College

  公开号：EP3034494A1

  公开（公告）日：2016-06-22

  The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

  本发明具有一系列抑制肿瘤坏死因子α（TNF-α）诱导坏死的杂环衍生物。本发明的杂环化合物由式(I)和(Ia)-(Ie)描述，并证明可抑制FADD缺陷变体人Jurkat T细胞中TNF-α诱导的坏死。本发明还具有以本发明化合物为特征的药物组合物。本发明的化合物和组合物还可用于治疗坏死可能起重要作用的疾病。
• Methods for treating spinal cord injury
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10022419B2

  公开（公告）日：2018-07-17

  Provided are methods for promoting axon regeneration of a Central Nervous System (CNS) neuron and promoting nerve function following injury to a CNS neuron, for example, brain and/or spinal cord injury. Axon regeneration in a CNS neuron or nerve function following injury to a CNS neuron can be promoted by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject suffering from a CNS disorder, wherein a symptom of the CNS disorder is axon degeneration.

  本文提供了促进中枢神经系统（CNS）神经元轴突再生和促进中枢神经系统神经元损伤后神经功能的方法，例如脑和/或脊髓损伤。中枢神经系统神经元的轴突再生或中枢神经系统神经元损伤后的神经功能可通过向患有中枢神经系统疾病的受试者单独施用坏死抑制剂或与凋亡抑制剂联合施用来促进，其中中枢神经系统疾病的症状是轴突变性。
• Methods and compositions for preserving retinal ganglion cells
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10617735B2

  公开（公告）日：2020-04-14

  Provided are methods and compositions for maintaining the viability of retinal ganglion cells in a subject with an ocular disorder including, for example, glaucoma and optic nerve injury. The viability of the retinal ganglion cells can be preserved by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject having an eye with the ocular condition. The compositions, when administered, maintain the viability of the cells and/or promote axon regeneration, thereby minimizing the loss of vision or visual function associated with the ocular disorder.

  本发明提供了维持患有眼部疾病（例如青光眼和视神经损伤）的患者视网膜神经节细胞活力的方法和组合物。通过向患有眼部疾病的患者单独施用坏死抑制剂或与凋亡抑制剂联合施用，可保持视网膜神经节细胞的活力。给药后，组合物可维持细胞的活力和/或促进轴突再生，从而最大程度地减少与眼部疾病相关的视力或视觉功能的丧失。