2-(N-pyrrolidinyl)-3'-methylpropiophenone | 1214940-01-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(N-pyrrolidinyl)-3'-methylpropiophenone
• 英文别名: 1-(3-Methylphenyl)-2-(1-pyrrolidinyl)-1-propanone；1-(3-methylphenyl)-2-pyrrolidin-1-ylpropan-1-one
• CAS: 1214940-01-8
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: BYYSWQHJMWVSGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(N-pyrrolidinyl)-3'-methylpropiophenone 、 富马酸 以 甲醇 、 乙醚 为溶剂， 以320 mg的产率得到2-(N-pyrrolidinyl)-3'-methylpropiophenone fumarate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Smoking Cessation

  摘要：

  Bupropion (2a) analogues were synthesized and tested for their ability to inhibit monoamine uptake and to antagonize the effects of human alpha 3 beta 4*, alpha 4 beta 2, alpha 4 beta 4, and alpha 1* nAChRs. The analogues were evaluated for their ability to block nicotine-induced effects in four tests in mice. Nine analogues showed increased monoamine uptake inhibition. Similar to 2a, all but one analogue show inhibition of nAChR function selective for human alpha 3 beta 4*-nAChR. Nine analogues have higher affinity at alpha 3 beta 4*-nAChRs than 2a. Four analogues also had higher affinity for alpha 4 beta 2 nAChR. Analogues 2r, 2m, and 2n with AD(50) values of 0.014, 0.015, and 0.028 mg/kg were 87, 8 1, and 43 times more potent than 2a in blocking nicotine-induced antinociception in the tail-nick test. Analogue 2x with IC50 values of 31 and 180 nM for DA and NE, respectively, and with IC50 of 0.62 and 9.8 mu m for antagonism of alpha 3 beta 4 and alpha 4 beta 2 nAChRs had the best overall in vitro profile relative to 2a.

  DOI：

  10.1021/jm9017465
• 作为产物：
  描述：

  四氢吡咯 、 2-溴-1-苯基-1-丁酮 以 水 、 乙腈 为溶剂， 反应 4.0h， 生成 2-(N-pyrrolidinyl)-3'-methylpropiophenone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Smoking Cessation

  摘要：

  Bupropion (2a) analogues were synthesized and tested for their ability to inhibit monoamine uptake and to antagonize the effects of human alpha 3 beta 4*, alpha 4 beta 2, alpha 4 beta 4, and alpha 1* nAChRs. The analogues were evaluated for their ability to block nicotine-induced effects in four tests in mice. Nine analogues showed increased monoamine uptake inhibition. Similar to 2a, all but one analogue show inhibition of nAChR function selective for human alpha 3 beta 4*-nAChR. Nine analogues have higher affinity at alpha 3 beta 4*-nAChRs than 2a. Four analogues also had higher affinity for alpha 4 beta 2 nAChR. Analogues 2r, 2m, and 2n with AD(50) values of 0.014, 0.015, and 0.028 mg/kg were 87, 8 1, and 43 times more potent than 2a in blocking nicotine-induced antinociception in the tail-nick test. Analogue 2x with IC50 values of 31 and 180 nM for DA and NE, respectively, and with IC50 of 0.62 and 9.8 mu m for antagonism of alpha 3 beta 4 and alpha 4 beta 2 nAChRs had the best overall in vitro profile relative to 2a.

  DOI：

  10.1021/jm9017465

文献信息

• Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Smoking Cessation
  作者：F. Ivy Carroll、Bruce E. Blough、S. Wayne Mascarella、Hernán A. Navarro、J. Brek Eaton、Ronald J. Lukas、M. Imad Damaj

  DOI：10.1021/jm9017465

  日期：2010.3.11

  Bupropion (2a) analogues were synthesized and tested for their ability to inhibit monoamine uptake and to antagonize the effects of human alpha 3 beta 4*, alpha 4 beta 2, alpha 4 beta 4, and alpha 1* nAChRs. The analogues were evaluated for their ability to block nicotine-induced effects in four tests in mice. Nine analogues showed increased monoamine uptake inhibition. Similar to 2a, all but one analogue show inhibition of nAChR function selective for human alpha 3 beta 4*-nAChR. Nine analogues have higher affinity at alpha 3 beta 4*-nAChRs than 2a. Four analogues also had higher affinity for alpha 4 beta 2 nAChR. Analogues 2r, 2m, and 2n with AD(50) values of 0.014, 0.015, and 0.028 mg/kg were 87, 8 1, and 43 times more potent than 2a in blocking nicotine-induced antinociception in the tail-nick test. Analogue 2x with IC50 values of 31 and 180 nM for DA and NE, respectively, and with IC50 of 0.62 and 9.8 mu m for antagonism of alpha 3 beta 4 and alpha 4 beta 2 nAChRs had the best overall in vitro profile relative to 2a.