4-(1-pyrazolylmethyl)-N-hydroxybenzamide | 1392835-64-1

• 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-(1-pyrazolylmethyl)-N-hydroxybenzamide
• 英文别名: 4-((1H-pyrazol-1-yl)methyl)-N-hydroxybenzamide；N-hydroxy-4-(pyrazol-1-ylmethyl)benzamide
• CAS: 1392835-64-1
• 化学式: C₁₁H₁₁N₃O₂
• 分子量: 217.227
• InChiKey: DUGDSZFLAKVUEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  甲基 4-(1H-吡唑-1-甲基)苯甲酸 在 羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.25h， 以56%的产率得到4-(1-pyrazolylmethyl)-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。
• Selective HDAC6 inhibitors
  申请人：ITALFARMACO S.P.A.

  公开号：US11351178B2

  公开（公告）日：2022-06-07

  The present invention relates to novel benzohydroxamic compounds of formula (I) and (II) and pharmaceutically acceptable salts, isomers and prodrugs thereof, exhibiting a high selective inhibitory activity against histone deacetylase 6 (HDAC6) enzyme.

  本发明涉及式（I）和（II）的新型苯羟肟类化合物及其药学上可接受的盐、异构体和原药，它们对组蛋白去乙酰化酶 6（HDAC6）酶具有高选择性抑制活性。
• 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
• Selective HDAC6 Inhibitors
  申请人：ITALFARMACO S.P.A.

  公开号：US20210128577A1

  公开（公告）日：2021-05-06

  The present invention relates to novel benzohydroxamic compounds of formula (1) and (II) and pharmaceutically acceptable salts, isomers and prodrugs thereof, exhibiting a high selective inhibitory activity against histone deacetylase 6 (HDAC6) enzyme.
• US9249087B2
  申请人：——

  公开号：US9249087B2

  公开（公告）日：2016-02-02