N-(2-hydroxy-2-pyridin-3-ylethyl)-6-[5-(trifluoromethyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]pyridazine-3-carboxamide | 1024604-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-(2-hydroxy-2-pyridin-3-ylethyl)-6-[5-(trifluoromethyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]pyridazine-3-carboxamide
• 英文别名: N-(2-hydroxy-2-(pyridin-3-yl)ethyl)-6-(5-(trifluoromethyl)spiro[chroman-2,4''-piperidine]-1''-yl)pyridazine-3-carboxamide；N-(2-hydroxy-2-pyridin-3-ylethyl)-6-[5-(trifluoromethyl)spiro[3,4-dihydrochromene-2,4'-piperidine]-1'-yl]pyridazine-3-carboxamide
• CAS: 1024604-70-3
• 化学式: C₂₆H₂₆F₃N₅O₃
• 分子量: 513.519
• InChiKey: WLOLMYNNISZAOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-chloropyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide 、 5-trifluoromethyl-3,4-dihydro-1'H-spiro(chromene-2,4'-piperidine)-1'-carboxylate hydrochloride 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 48.0h， 以49%的产率得到N-(2-hydroxy-2-pyridin-3-ylethyl)-6-[5-(trifluoromethyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]pyridazine-3-carboxamide
  参考文献：
  名称：

  Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]

  摘要：

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.043