1-(methylsulfonyl)-N-[4-(pyridin-3-yl)phenyl]-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide | 1185761-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(methylsulfonyl)-N-[4-(pyridin-3-yl)phenyl]-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide
• 英文别名: 1-(methylsulfonyl)-N-(4-(pyridin-3-yl)phenyl)spiro[indoline-3,4''-piperidine]-1''-carboxamide；1-methylsulfonyl-N-(4-pyridin-3-ylphenyl)spiro[2H-indole-3,4'-piperidine]-1'-carboxamide
• CAS: 1185761-74-3
• 化学式: C₂₅H₂₆N₄O₃S
• 分子量: 462.572
• InChiKey: YFVXIRYDRAPMQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  91
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(methylsulfonyl)-N-[4-(pyridin-3-yl)phenyl]-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 1-(methylsulfonyl)-N-[4-(pyridin-3-yl)phenyl]-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide hydrochloride
  参考文献：
  名称：

  新型口服活性NPY Y5受体拮抗剂：螺吲哚啉类化合物的合成及其构效关系

  摘要：

  合成了设计用作NPY Y5受体拮抗剂的螺吲哚啉脲衍生物，并研究了它们的结构-活性关系。在这些衍生物中，化合物3a显示出良好的Y5结合亲和力和良好的药代动力学性质。化合物3a显着抑制了bPP Y5激动剂诱导的大鼠食物摄取，并抑制了DIO小鼠的体重增加。

  DOI：

  10.1016/j.bmc.2009.05.064
• 作为产物：
  描述：

  phenyl N-(4-pyridin-3-ylphenyl)carbamate 、 1-(甲基磺酰基)螺[吲哚啉-3,4’-哌啶] 在 三乙胺 作用下， 以 氯仿 为溶剂， 生成 1-(methylsulfonyl)-N-[4-(pyridin-3-yl)phenyl]-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxamide
  参考文献：
  名称：

  Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists

  摘要：

  A series of spiroindoline-3,40-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats. Some of the antagonists showed good oral bioavailability and/ or good brain penetration. In particular, compound 6e was orally bioavailable and brain penetrant, and oral administration of 6e inhibited bPP-induced food intake in rats with a minimum effective dose of 10 mg/ kg. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.02.035

文献信息

• Novel orally active NPY Y5 receptor antagonists: Synthesis and structure–activity relationship of spiroindoline class compounds
  作者：Toshihiro Sakamoto、Minoru Moriya、Hiroyasu Tsuge、Toshiyuki Takahashi、Yuji Haga、Katsumasa Nonoshita、Osamu Okamoto、Hirobumi Takahashi、Aya Sakuraba、Tomoko Hirohashi、Takunobu Shibata、Tetsuya Kanno、Junko Ito、Hisashi Iwaasa、Akira Gomori、Akane Ishihara、Takahiro Fukuroda、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmc.2009.05.064

  日期：2009.7

  Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure–activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic properties. Compound 3a significantly inhibited bPP Y5 agonist-induced food intake in rats, and suppressed body weight gain in DIO mice.

  合成了设计用作NPY Y5受体拮抗剂的螺吲哚啉脲衍生物，并研究了它们的结构-活性关系。在这些衍生物中，化合物3a显示出良好的Y5结合亲和力和良好的药代动力学性质。化合物3a显着抑制了bPP Y5激动剂诱导的大鼠食物摄取，并抑制了DIO小鼠的体重增加。
• Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists
  作者：Toshihiro Sakamoto、Minoru Moriya、Yuji Haga、Toshiyuki Takahashi、Takunobu Shibata、Osamu Okamoto、Katsumasa Nonoshita、Hidefumi Kitazawa、Masayasu Hidaka、Akira Gomori、Hisashi Iwaasa、Akane Ishihara、Akio Kanatani、Takehiro Fukami、Ying-Duo Gao、Douglas J. MacNeil、Lihu Yang

  DOI：10.1016/j.bmcl.2009.02.035

  日期：2009.3

  A series of spiroindoline-3,40-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats. Some of the antagonists showed good oral bioavailability and/ or good brain penetration. In particular, compound 6e was orally bioavailable and brain penetrant, and oral administration of 6e inhibited bPP-induced food intake in rats with a minimum effective dose of 10 mg/ kg. (C) 2009 Published by Elsevier Ltd.