(2R,4S)-4-azido-1-benzyl-2-carbomethoxypyrrolidine | 114676-55-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S)-4-azido-1-benzyl-2-carbomethoxypyrrolidine
• 英文别名: (2R,4S)-4-Azido-1-benzyl-2-methoxycarbonylpyrrolidine；(2R,4S)-methyl 4-azido-1-benzylpyrrolidine-2-carboxylate；methyl (2R,4S)-4-azido-1-benzylpyrrolidine-2-carboxylate
• CAS: 114676-55-0
• 化学式: C₁₃H₁₆N₄O₂
• 分子量: 260.296
• InChiKey: WLLZXDRXTRGAAO-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.11
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  78.3
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-azido-1-benzyl-2-carbomethoxypyrrolidine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以94%的产率得到((2R,4S)-4-azido-1-benzylpyrrolidin-2-yl)methanol
  参考文献：
  名称：

  A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

  摘要：

  This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 mu M in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.116
• 作为产物：
  描述：

  顺式-4-羟基-D-脯氨酸盐酸盐 在 氯化亚砜 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 (2R,4S)-4-azido-1-benzyl-2-carbomethoxypyrrolidine
  参考文献：
  名称：

  A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

  摘要：

  This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 mu M in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.116

文献信息

• Design, synthesis, and properties of (4S)-7-(4-amino-2-substituted-pyrrolidin-1-yl)quinolone-3-carboxylic acids
  作者：Terry Rosen、Daniel T. W. Chu、Isabella M. Lico、Prabhavathi B. Fernandes、Kennan Marsh、Linus Shen、Valerie G. Cepa、Andre G. Pernet

  DOI：10.1021/jm00403a020

  日期：1988.8

  The quinolonecarboxylic acids constitute a class of extremely potent and orally active broad-spectrum antibacterial agents. These compounds have been shown to inhibit DNA gyrase, a key enzyme in bacterial DNA replication. The 7-(3-aminopyrrolidinyl)quinolone A-60969 (1) is a particularly potent member of this class and is currently undergoing clinical evaluation. We have studied a series of enantiomerically

  喹诺酮羧酸构成一类非常有效且具有口服活性的广谱抗菌剂。这些化合物已显示出抑制DNA回旋酶的作用，而DNA回旋酶是细菌DNA复制中的关键酶。7-（3-氨基吡咯烷基）喹诺酮A-60969（1）是此类中特别有效的成员，目前正在临床评估中。我们已经研究了一系列对映体均质的（4S）-7-（4-氨基-2-取代的吡咯烷基）喹诺酮类药物，以利用吡咯烷部分的2位改善此类药物的溶解度和药代动力学性质化合物，同时仍保持有效的抗菌活性。我们已经发现，在吡咯烷环的2-位上的绝对立体化学对于维持这种活性至关重要。在本文中，我们报告了该系列化合物的不对称合成以及体外和体内结构-活性关系的完整详细信息，以及与结构修饰相关的理化特性，例如水溶性和logP。我们还讨论了这些化合物中的几种在小鼠中的药代动力学特性，以及在本研究中在狗中具有最佳药物总体特性的59的药代动力学。
• Asymmetric Synthesis of 2-Substituted (4<i>S</i>)-4-Aminopyrrolidines. S_N2 Displacement at the 4-Position of the Pyrrolidine Moiety
  作者：Terry Rosen、Stephen W. Fesik、Daniel T. W. Chu、André G. Pernet

  DOI：10.1055/s-1988-27459

  日期：——

  The trans-disubstituted-N-benzyl pyrrolidine 10 is prepared in enantiomerically homogeneous form from cis-4-hydroxy-D-proline (4) in an efficient sequence. The key step involves an SN2 displacement of the methanesulfonate of alcohol 5 with azide ion and occurs without participation of the basic ring nitrogen. The stereochemical outcome, which is contrary to that reported for the related systems 15 and 16, suggests that a mechanism involving the proposed intermediate 19a is improbable. The cis-derivative 14 is prepared by an identical sequence of reactions beginning with trans-4-hydroxy-L-proline. Compound 10 is the precursor to the potent DNA gyrase inhibitor 1 and several related analogs.

  反式二取代的N-苄基吡咯烷10是通过高效的反应序列从顺式-4-氢氧基-D-脯氨酸(4)制备得到的，且具有对映体均匀性。关键步骤涉及醇5的甲磺酸酯与叠氮离子的SN2取代反应，并且在此过程中不涉及基本环氮原子的参与。其立体化学结果与相关系统15和16的报告相反，表明涉及所提出的中间体19a的机制是不太可能的。顺式衍生物14是通过与反式-4-氢氧基-L-脯氨酸相同的反应序列制备的。化合物10是强效DNA旋转酶抑制剂1及其若干相关类药物的前体。
• ROSEN, TERRY;LICO, ISABELLA M.;CHU, DANIEL T. W., J. ORG. CHEM., 53,(1988) N 7, 1580-1582
  作者：ROSEN, TERRY、LICO, ISABELLA M.、CHU, DANIEL T. W.

  DOI：——

  日期：——
• ROSEN, TERRY;CHU, DANIEL T. W.;LICO, ISABELLA M.;FERNANDES, PRABHAVATHI B+, J. MED. CHEM., 31,(1988) N 8, C. 1598-1611
  作者：ROSEN, TERRY、CHU, DANIEL T. W.、LICO, ISABELLA M.、FERNANDES, PRABHAVATHI B+

  DOI：——

  日期：——