2-chloro-5-(5-methyl-1H-pyrazol-1-yl)-N-(6-(1-methylpiperidin-4-ylsulfonyl)benzo[d]thiazol-2-ylcarbamoyl)benzamide | 1619235-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-5-(5-methyl-1H-pyrazol-1-yl)-N-(6-(1-methylpiperidin-4-ylsulfonyl)benzo[d]thiazol-2-ylcarbamoyl)benzamide
• 英文别名: 2-chloro-N-[[6-(1-methylpiperidin-4-yl)sulfonyl-1,3-benzothiazol-2-yl]carbamoyl]-5-(5-methylpyrazol-1-yl)benzamide
• CAS: 1619235-92-5
• 化学式: C₂₅H₂₅ClN₆O₄S₂
• 分子量: 573.096
• InChiKey: ZQTZJYORDKSGOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(2-aminobenzothiazol-6-ylsulfonyl)piperidine-1-carboxylate 在 盐酸 、 sodium cyanoborohydride 、 乙酰氯 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 4.58h， 生成 2-chloro-5-(5-methyl-1H-pyrazol-1-yl)-N-(6-(1-methylpiperidin-4-ylsulfonyl)benzo[d]thiazol-2-ylcarbamoyl)benzamide
  参考文献：
  名称：

  Identification, Optimization, and Pharmacology of Acylurea GHS-R1a Inverse Agonists

  摘要：

  Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.

  DOI：

  10.1021/jm500610n