1'-[6-[5-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-3-yl]pyridazin-3-yl]-5-(trifluoromethyl)spiro[3,4-dihydrochromene-2,4'-piperidine] | 1207163-51-6

• 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: 1'-[6-[5-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-3-yl]pyridazin-3-yl]-5-(trifluoromethyl)spiro[3,4-dihydrochromene-2,4'-piperidine]
• CAS: 1207163-51-6
• 化学式: C₂₆H₂₄F₃N₇O
• 分子量: 507.518
• InChiKey: SIGGFDISUSMMKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(吡啶-3-基)乙酸肼 、 6-(5-(trifluoromethyl)spiro[chromane-2,4'-piperidin]-1'-yl)pyridazine-3-carbonitrile 在 sodium methylate 、 乙酸酐 作用下， 以 甲醇 为溶剂， 以80%的产率得到1'-[6-[5-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-3-yl]pyridazin-3-yl]-5-(trifluoromethyl)spiro[3,4-dihydrochromene-2,4'-piperidine]
  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