(S)-N-((1-Boc-pyrrolidin-2-yl)-methyl)-2-aminobenzamide | 937701-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-N-((1-Boc-pyrrolidin-2-yl)-methyl)-2-aminobenzamide
• 英文别名: (S)-1-Boc-2-((2-aminobenzamido)methyl)pyrrolidine；tert-butyl (2S)-2-[[(2-aminobenzoyl)amino]methyl]pyrrolidine-1-carboxylate
• CAS: 937701-79-6
• 化学式: C₁₇H₂₅N₃O₃
• 分子量: 319.404
• InChiKey: JDKVWWACNFNHOB-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-N-((1-Boc-pyrrolidin-2-yl)-methyl)-2-aminobenzamide 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 51.0h， 生成 (S)-N-(2-((1-(3,4-dimethoxyphenethyl)pyrrolidin-2-yl)methylcarbamoyl)phenyl)quinoline-3-carboxamide
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.03.014
• 作为产物：
  描述：

  (S)-1-Boc-2-((2-nitrobenzamido)methyl)pyrrolidine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以94%的产率得到(S)-N-((1-Boc-pyrrolidin-2-yl)-methyl)-2-aminobenzamide
  参考文献：
  名称：

  具有双氢键电势的​​功能化脯氨酸：在盐水中将高羰基化合物对映体选择性地加成羰基化合物至β-硝基苯乙烯

  摘要：

  简单地合成S-脯氨酸即可获得脯氨酰胺5 – 7作为能够双氢键合的有机催化剂，用于羰基化合物与β-硝基苯乙烯的对映选择性迈克尔加成反应。结果表明，脯氨酰胺催化剂7导致具有高非对映选择性和对映选择性的加成产物。据信涉及通过两个H键结合亲电硝基苯乙烯的过渡态结构通过由甲苯磺酰基环介导的π，π堆积相互作用而进一步稳定。

  DOI：

  10.1016/j.tetlet.2010.07.164

文献信息

• In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)
  作者：Philippe Labrie、Shawn P. Maddaford、Jacques Lacroix、Concettina Catalano、David K.H. Lee、Suman Rakhit、René C. Gaudreault

  DOI：10.1016/j.bmc.2007.03.014

  日期：2007.6.1

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.
• Functionalized proline with double hydrogen bonding potential: highly enantioselective Michael addition of carbonyl compounds to β-nitrostyrenes in brine
  作者：Satyajit Saha、Saona Seth、Jarugu Narasimha Moorthy

  DOI：10.1016/j.tetlet.2010.07.164

  日期：2010.10

  synthetic manipulation of S-proline allows access to prolinamides 5–7 as organocatalysts capable of double hydrogen bonding for enantioselective Michael addition reactions of carbonyl compounds to β-nitrostyrenes. It is shown that prolinamide catalyst 7 leads to addition products with a high diastereo- as well as enantioselectivity. The transition state structure involving the binding of electrophilic

  简单地合成S-脯氨酸即可获得脯氨酰胺5 – 7作为能够双氢键合的有机催化剂，用于羰基化合物与β-硝基苯乙烯的对映选择性迈克尔加成反应。结果表明，脯氨酰胺催化剂7导致具有高非对映选择性和对映选择性的加成产物。据信涉及通过两个H键结合亲电硝基苯乙烯的过渡态结构通过由甲苯磺酰基环介导的π，π堆积相互作用而进一步稳定。