4-[(4-chlorobenzyl)oxy]-1-(2-cyclopropyl-1-methyl-1H-indol-6-yl)pyridin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-[(4-chlorobenzyl)oxy]-1-(2-cyclopropyl-1-methyl-1H-indol-6-yl)pyridin-2(1H)-one
• 英文别名: 4-[(4-Chlorophenyl)methoxy]-1-(2-cyclopropyl-1-methylindol-6-yl)pyridin-2-one；4-[(4-chlorophenyl)methoxy]-1-(2-cyclopropyl-1-methylindol-6-yl)pyridin-2-one
• 化学式: C₂₄H₂₁ClN₂O₂
• 分子量: 404.896
• InChiKey: HAFNACMEJSUIQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-溴-2-硝基苯酚 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙醇胺 、 sodium hydride 、 potassium carbonate 、 tin(ll) chloride 、 palladium dichloride 、 iron(II) chloride 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 4-[(4-chlorobenzyl)oxy]-1-(2-cyclopropyl-1-methyl-1H-indol-6-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test

  摘要：

  To develop non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists with a high probability of target selectivity and therapeutic window, we explored neutral bicyclic motifs that could replace the previously reported imidazo[1,2-a]pyridine or 1H-benzimidazole motif. The results indicated that the binding affinity of a chemically neutral 2H-indazole derivative 8a with MCHR1 (hMCHR1: IC50 = 35 nM) was comparable to that of the imidazopyridine and benzimidazole derivatives (1 and 2, respectively) reported so far. However, 8a was positive in the Ames test using TA1537 in S9- condition. Based on a putative intercalation of 8a with DNA, we introduced a sterically-hindering cyclopropyl group on the indazole ring to decrease planarity, which led to the discovery of 1-(2-cyclopropyl-3-methyl-2H-indazol- 5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy} pyridin-2(1H)-one 8l without mutagenicity in TA1537. Compound 8l exerted significant antiobesity effects in diet-induced obese F344 rats and exhibited promising safety profile. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.013