N-[4-[trans-2-aminocyclopropyl]phenyl]-3-(2-oxooxazolidin-3-yl)benzamide hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[4-[trans-2-aminocyclopropyl]phenyl]-3-(2-oxooxazolidin-3-yl)benzamide hydrochloride
• 英文别名: N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-3-(2-oxo-1,3-oxazolidin-3-yl)benzamide;hydrochloride
• 化学式: C₁₉H₁₉N₃O₃*ClH
• 分子量: 373.839
• InChiKey: BOBKEFAGKDQWKR-MCJVGQIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  84.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 20.0h， 生成 N-[4-[trans-2-aminocyclopropyl]phenyl]-3-(2-oxooxazolidin-3-yl)benzamide hydrochloride
  参考文献：
  名称：

  发现一种新型组蛋白赖氨酸特异性脱甲基酶1A（KDM1A / LSD1）抑制剂作为口服抗肿瘤药物

  摘要：

  我们报告一个新的系列反苯环丙胺（TCPA）衍生物的立体选择性合成和生物活性（14A - ķ，15，16），KDM1A的有效抑制剂。新化合物强烈抑制急性白血病细胞系的克隆形成潜力。特别地，在小鼠中评估了三种分子（14d，14e和14g）相对于MAOA具有选择性并且显着抑制THP-1人白血病细胞中的集落形成，其初步药代动力学。在小鼠急性早幼粒细胞白血病模型中进一步测试了14d和14e，得出14d最有效的。合成了它的两个对映异构体：（1 S，2 R）对映异构体15在生化和细胞分析中均显示出比其（1 R，2 S）类似物16高的活性。口服给药后，化合物15表现出体内功效，确定具有KDM1A抑制作用的小鼠白血病模型的存活率提高了62％。化合物15的生物学特性支持其作为癌症治疗剂的进一步研究。

  DOI：

  10.1021/acs.jmedchem.5b01209

文献信息

• Cyclopropylamine derivatives as histone demethylase inhibitors
  申请人：IEO - Istituto Europeo di Oncologia Srl

  公开号：EP2949648A1

  公开（公告）日：2015-12-02

  The present invention relates to cyclopropyl derivatives of general formula (I), wherein R1, and R2 are as defined in the specification. The present application also relates to pharmaceutical compositions containing such compounds and to their use in therapy.

  本发明涉及一般式(I)的环丙基衍生物，其中R1和R2如规范中所定义。本申请还涉及含有这种化合物的药物组合物，并其在治疗中的应用。
• Cyclopropylamine compounds as histone demethylase inhibitors
  申请人：IEO—Instituto Europeo di Oncologia S.r.l.

  公开号：US10233165B2

  公开（公告）日：2019-03-19

  The present disclosure relates to cyclopropyl compounds of general formula (I), wherein R1, and R2 are as defined in the specification. The present application also relates to pharmaceutical compositions containing such compounds and to their use in therapy.

  本公开涉及通式（I）的环丙基化合物，其中 R1 和 R2 如说明书中所定义。 本申请还涉及含有此类化合物的药物组合物及其在治疗中的应用。
• Reprogramming-based models of neurodevelopmental disorders and uses thereof
  申请人：IEO—Istituto Europeo di Oncologia S.r.l.

  公开号：US11369577B2

  公开（公告）日：2022-06-28

  The present invention relates to iPSC produced from fibroblast obtained from a subject affected by a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and uses thereof. The present invention also relates to a cortical neural progenitor cell or a terminally differentiated cortical glutamatergic or gabaergic neuronal cell or a neural crest stem cell line, a mesenchymal stem cell line produced from the iPSC or iPSC line. The invention also relates to method for identifying a compound for the treatment and/or prevention of a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and to a LSD1 inhibitor or a HDAC2 inhibitor for use in the treatment of such disorders.

  本发明涉及从患有神经发育障碍（包括智力障碍（ID）和/或属于自闭症谱系障碍（ASD）和/或精神分裂症（SZ））的受试者体内获得的成纤维细胞制备的iPSC及其用途。本发明还涉及一种皮质神经祖细胞或终末分化的皮质谷氨酸能或加巴能神经元细胞或神经嵴干细胞系、由iPSC或iPSC系产生的间充质干细胞系。本发明还涉及鉴定用于治疗和/或预防包含智力障碍（ID）的神经发育障碍和/或属于自闭症谱系障碍（ASD）和/或精神分裂症（SZ）的障碍的化合物的方法，以及用于治疗此类障碍的LSD1抑制剂或HDAC2抑制剂。
• CYCLOPROPYLAMINE COMPOUNDS AS HISTONE DEMETHYLASE INHIBITORS
  申请人：Istituto Europeo di Oncologia S.r.l.

  公开号：EP3148974A1

  公开（公告）日：2017-04-05
• REPROGRAMMING-BASED MODELS OF NEURODEVELOPMENTAL DISORDERS AND USES THEREOF
  申请人：IEO - Istituto Europeo di Oncologia S.r.l.

  公开号：US20190022027A1

  公开（公告）日：2019-01-24

  The present invention relates to iPSC produced from fibroblast obtained from a subject affected by a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and uses thereof. The present invention also relates to a cortical neural progenitor cell or a terminally differentiated cortical glutamatergic or gabaergic neuronal cell or a neural crest stem cell line, a mesenchymal stem cell line produced from the iPSC or iPSC line. The invention also relates to method for identifying a compound for the treatment and/or prevention of a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and to a LSD1 inhibitor or a HDAC2 inhibitor for use in the treatment of such disorders.