4-[(diethylamino)methyl]-N-hydroxybenzamide | 1392835-70-9

• 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: 4-[(diethylamino)methyl]-N-hydroxybenzamide
• 英文别名: 4-(diethylaminomethyl)-N-hydroxybenzamide
• CAS: 1392835-70-9
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: ZKULTALXLHDKIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N,N-二乙基-4-氨甲基苯甲酸甲酯 在 羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.25h， 以83%的产率得到4-[(diethylamino)methyl]-N-hydroxybenzamide
  参考文献：
  名称：

  Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome

  摘要：

  Disease-modifying therapies are needed for Fragile X Syndrome (FXS), as at present there are no effective treatments or cures. Herein, we report on a tetrahydroquinoline-based selective histone deacetylase 6 (HDAC6) inhibitor SW-100, its pharmacological and ADMET properties, and its ability to improve upon memory performance in a mouse model of FXS, Fmr1-1- mice. This small molecule demonstrates good brain penetrance, low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM), with at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms. Moreover, through its inhibition of the alpha-tubulin deacetylase domain of HDAC6 (CD2), in cells SW-100 upregulates alpha-tubulin acetylation with no effect on histone acetylation and selectively restores the impaired acetylated alpha-tubulin levels in the hippocampus of Fmr1(-/-) mice. Lastly, SW-100 ameliorates several memory and learning impairments in Fmr1(-/-) mice, thus modeling the intellectual deficiencies associated with FXS, and hence providing a strong rationale for pursuing HDAC6-based therapies for the treatment of this rare disease.

  DOI：

  10.1021/acschemneuro.8b00600

文献信息

• HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：Kozikowski Alan

  公开号：US20140128408A1

  公开（公告）日：2014-05-08

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.

  本发明公开了组蛋白去乙酰化酶抑制剂（HDACIs）及其组成物。公开了治疗疾病和状况的方法，其中抑制HDAC提供了益处，如癌症、神经退行性疾病、周围神经病变、神经疾病、创伤性脑损伤、中风、高血压、疟疾、自身免疫疾病、自闭症、自闭症谱系障碍和炎症。
• N-HYDROXYBENZAMIDE DERIVATIVES AS HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2670733B1

  公开（公告）日：2019-04-10
• US9249087B2
  申请人：——

  公开号：US9249087B2

  公开（公告）日：2016-02-02
• USRE47009E1
  申请人：——

  公开号：USRE47009E1

  公开（公告）日：2018-08-28
• [EN] HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS DE HDAC ET PROCÉDÉS THÉRAPEUTIQUES LES UTILISANT
  申请人：UNIV ILLINOIS

  公开号：WO2012106343A2

  公开（公告）日：2012-08-09

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.