1-(1,3-benzothiazol-2-yl)-3-hexyl-urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 1-(1,3-benzothiazol-2-yl)-3-hexyl-urea
• 英文别名: 1-(1,3-benzothiazol-2-yl)-3-hexylurea
• 化学式: C₁₄H₁₉N₃OS
• 分子量: 277.39
• InChiKey: KESBMEGTLWDJME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基苯并噻唑 、 异氰酸己酯 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 5.0h， 以64%的产率得到1-(1,3-benzothiazol-2-yl)-3-hexyl-urea
  参考文献：
  名称：

  Pharmacophore Identification and Scaffold Exploration to Discover Novel, Potent, and Chemically Stable Inhibitors of Acid Ceramidase in Melanoma Cells

  摘要：

  Acid ceramidase (AC) hydrolyzes ceramides, which are central lipid messengers for metabolism and signaling of sphingolipids. A growing body of evidence links deregulation of sphingolipids to several diseases, including cancer. Indeed, AC expression is abnormally high in melanoma cells. AC inhibition may thus be key to treating malignant melanoma. Here, we have used a systematic scaffold exploration to design a general pharmacophore for AC inhibition. This pharmacophore comprises a 6 + 5 fused ring heterocycle linked to an aliphatic substituent via a urea moiety. We have thus identified the novel benzimidazole derivatives 10, 21, 27, and 30, which are highly potent AC inhibitors. Their chemical and metabolic stabilities are comparable or superior to those of previously reported AC inhibitors. Moreover, they are potent against endogenous AC in intact melanoma cells. These novel inhibitors merit further characterization and can serve as a promising starting point for the discovery of new antimelanoma therapeutics.

  DOI：

  10.1021/acs.jmedchem.7b00472

文献信息

• Pharmacophore Identification and Scaffold Exploration to Discover Novel, Potent, and Chemically Stable Inhibitors of Acid Ceramidase in Melanoma Cells
  作者：Jose Antonio Ortega、Jose M. Arencibia、Giuseppina La Sala、Marco Borgogno、Inga Bauer、Luca Bono、Clarissa Braccia、Andrea Armirotti、Stefania Girotto、Anand Ganesan、Marco De Vivo

  DOI：10.1021/acs.jmedchem.7b00472

  日期：2017.7.13

  Acid ceramidase (AC) hydrolyzes ceramides, which are central lipid messengers for metabolism and signaling of sphingolipids. A growing body of evidence links deregulation of sphingolipids to several diseases, including cancer. Indeed, AC expression is abnormally high in melanoma cells. AC inhibition may thus be key to treating malignant melanoma. Here, we have used a systematic scaffold exploration to design a general pharmacophore for AC inhibition. This pharmacophore comprises a 6 + 5 fused ring heterocycle linked to an aliphatic substituent via a urea moiety. We have thus identified the novel benzimidazole derivatives 10, 21, 27, and 30, which are highly potent AC inhibitors. Their chemical and metabolic stabilities are comparable or superior to those of previously reported AC inhibitors. Moreover, they are potent against endogenous AC in intact melanoma cells. These novel inhibitors merit further characterization and can serve as a promising starting point for the discovery of new antimelanoma therapeutics.