2-oxo-N-(4-phenylbutyl)benzoxazole-3(2H)-carbothioamide

• 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: 2-oxo-N-(4-phenylbutyl)benzoxazole-3(2H)-carbothioamide
• 英文别名: 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carbothioamide
• 化学式: C₁₈H₁₈N₂O₂S
• 分子量: 326.419
• InChiKey: SSCDPZUHFAOLRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苯并唑啉酮 、 4-苯丁基异硫氰酸盐 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 20.0h， 以5%的产率得到2-oxo-N-(4-phenylbutyl)benzoxazole-3(2H)-carbothioamide
  参考文献：
  名称：

  Benzoxazolone Carboxamides: Potent and Systemically Active Inhibitors of Intracellular Acid Ceramidase

  摘要：

  摘要神经酰胺是一种生物活性脂质信使，参与控制细胞衰老、炎症和凋亡。神经酰胺在酸性神经酰胺酶（AC）的水解作用下停止了这些物质的生物活性，并影响正常细胞和肿瘤细胞的存活和功能。由于 AC 在神经酰胺代谢中的核心作用，它可能为神经酰胺介导的信号传导失调症提供一个新的分子靶点。在本研究中，一类苯并恶唑酮羧酰胺类化合物被鉴定为第一种强效、全身活性的神经酰胺抑制剂。该类化合物的原型成员通过与催化半胱氨酸共价结合，以低纳摩尔的效力抑制 AC。它们的代谢稳定性和高体内疗效表明，这些化合物可用作探针来研究神经酰胺在健康和疾病中的作用，而且这种支架可能是开发新型治疗药物的一个很有前景的起点。

  DOI：

  10.1002/anie.201409042

文献信息

• [EN] BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS<br/>[FR] DÉRIVÉS DE BENZOXAZOLONE EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE, ET LEUR UTILISATION COMME MÉDICAMENTS
  申请人：FOND ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：WO2015173168A1

  公开（公告）日：2015-11-19

  The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

  本发明涉及苯并噁唑酮衍生物作为酸酶抑制剂，含有这些抑制剂的药物组合物以及用于抑制酸酶治疗临床相关的调节神经酰胺水平的疾病的方法。该发明还提供苯并噁唑酮衍生物作为药物在治疗癌症、炎症、疼痛、炎症性疼痛或肺部疾病中的用途。
• Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
  申请人：FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：US10226452B2

  公开（公告）日：2019-03-12

  The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

  本发明涉及作为酸性神经酰胺酶抑制剂的苯并恶唑酮衍生物、含有这些抑制剂的药物组合物和抑制酸性神经酰胺酶的方法，用于治疗神经酰胺水平的调节与临床相关的疾病。本发明还提供了用作治疗癌症、炎症、疼痛、炎性疼痛或肺部疾病的药物的苯并恶唑酮衍生物。
• BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS
  申请人：FONDAZIONE ISTITUTO ITALIANO DI TECHOLOGIA

  公开号：US20170182010A1

  公开（公告）日：2017-06-29

  The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.
• METHODS AND COMPOSITIONS FOR TREATING LYSOSOMAL STORAGE DISORDERS
  申请人：Lysosomal Therapeutics Inc.

  公开号：US20180369210A1

  公开（公告）日：2018-12-27

  The invention relates to a method of treating lysosomal storage disorders caused by a deficiency in lysosomal hydrolase activity. The method comprises administering an effective amount of an acid ceramidase inhibitor to the subject thereby to treat the lysosomal storage disorder.
• METHODS AND COMPOSITIONS FOR TREATING NEURODEGENERATIVE DISORDERS
  申请人：Lysosomal Therapeutics Inc.

  公开号：US20180369211A1

  公开（公告）日：2018-12-27

  The invention relates to the treatment of neurodegenerative disorders with ceramidase inhibitor.