methyl(2-piperidin-1-ylethyl)carbamylchloride | 936691-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl(2-piperidin-1-ylethyl)carbamylchloride
• 英文别名: N-methyl-N-(2-piperidin-1-ylethyl)carbamoyl chloride
• CAS: 936691-71-3
• 化学式: C₉H₁₇ClN₂O
• 分子量: 204.7
• InChiKey: FTEXZUSWQPDHLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-苯基哌啶-4-甲腈 、 methyl(2-piperidin-1-ylethyl)carbamylchloride 在 N,N-二异丙基乙胺 作用下， 以 氯仿 为溶剂， 反应 4.0h， 生成 4-cyano-N-methyl-4-phenyl-N-(2-(piperidin-1-yl)ethyl)piperidine-1-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of a spiro-isobenzofuranone class of histamine H3 receptor inverse agonists

  摘要：

  Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain-penetrable non-imidazole H-3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t-x. Spiro-isobenzofuranone 2x, the most potent among the derivatives, was converted to the corresponding amide 1a, which possessed dramatically improved H3 activity (IC50 = 0.72 nM; more than 20-fold improvement over 2x). Further elaboration led to the identification of 1b, a 5-methoxy derivative with an IC50 of 0.54 nM. Our studies demonstrated that derivatives 1a and 1b to be potent, selective, and brain-penetrable H-3 inverse agonists. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.125
• 作为产物：
  描述：

  甲基-(2-哌啶-1-乙基)-胺 、 三光气 在 N,N-二异丙基乙胺 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 methyl(2-piperidin-1-ylethyl)carbamylchloride
  参考文献：
  名称：

  Synthesis and evaluation of a spiro-isobenzofuranone class of histamine H3 receptor inverse agonists

  摘要：

  Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain-penetrable non-imidazole H-3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t-x. Spiro-isobenzofuranone 2x, the most potent among the derivatives, was converted to the corresponding amide 1a, which possessed dramatically improved H3 activity (IC50 = 0.72 nM; more than 20-fold improvement over 2x). Further elaboration led to the identification of 1b, a 5-methoxy derivative with an IC50 of 0.54 nM. Our studies demonstrated that derivatives 1a and 1b to be potent, selective, and brain-penetrable H-3 inverse agonists. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.125

文献信息

• Synthesis and evaluation of a spiro-isobenzofuranone class of histamine H3 receptor inverse agonists
  作者：Makoto Jitsuoka、Daisuke Tsukahara、Sayaka Ito、Takeshi Tanaka、Norihiro Takenaga、Shigeru Tokita、Nagaaki Sato

  DOI：10.1016/j.bmcl.2008.07.125

  日期：2008.9

  Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain-penetrable non-imidazole H-3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t-x. Spiro-isobenzofuranone 2x, the most potent among the derivatives, was converted to the corresponding amide 1a, which possessed dramatically improved H3 activity (IC50 = 0.72 nM; more than 20-fold improvement over 2x). Further elaboration led to the identification of 1b, a 5-methoxy derivative with an IC50 of 0.54 nM. Our studies demonstrated that derivatives 1a and 1b to be potent, selective, and brain-penetrable H-3 inverse agonists. (C) 2008 Elsevier Ltd. All rights reserved.