dimethyl (2R)-2-(benzylideneamino)butanedioate | 1584725-20-1

• 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: dimethyl (2R)-2-(benzylideneamino)butanedioate
• CAS: 1584725-20-1
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: SYHFTHGTZXTEKV-LLVKDONJSA-N

物化性质

• 沸点：
  352.6±32.0 °C(predicted)
• 密度：
  1.11±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  65
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl (2R)-2-(benzylideneamino)butanedioate 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.25h， 生成 methyl (R)-2-[1-benzyl-4-(cyclohexylmethyl)-3,6-dioxopiperazin-2-yl]acetate
  参考文献：
  名称：

  Synthesis, Pharmacological Evaluation, and σ₁ Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines

  摘要：

  Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. sigma receptor affinity was recorded using receptor material from both animal and human origin, sigma(1) affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yliethanol (7c) revealed the highest affinity at human sigma(1) receptors (K-i = 6.8 nM). The potent a, receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the a, receptor was analyzed in detail using the 3D homology model of the sigma(1) receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human a, receptor.

  DOI：

  10.1021/jm401707t
• 作为产物：
  描述：

  苯甲醛 、 D-天冬氨酸二甲酯盐酸盐 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 dimethyl (2R)-2-(benzylideneamino)butanedioate
  参考文献：
  名称：

  2-(2-羟乙基)哌嗪衍生物作为有效的人碳酸酐酶抑制剂：合成、酶抑制、计算研究和抗青光眼活性

  摘要：

  靶向碳酸酐酶 (CA) 代表了一种治疗从青光眼到癌症的多种疾病的策略。为了拓宽我们的系列哌嗪的构效关系 (SAR)，这些哌嗪具有有效的人碳酸酐酶 (hCA) 抑制作用，制备了一系列带有 (2-羟乙基) 基团的新手性哌嗪。Zn 结合功能，即 4-氨磺酰基苯甲酰基部分，与一个哌嗪 N 原子相连，而另一个氮被烷基取代基修饰。与用于合成先前报道的系列的方法类似，新化合物的制备从 ( R )- 和 ( S）-天冬氨酸。在合成过程中发生了部分外消旋化。为了克服这个问题，研究了其他化学策略。使用停流CO 2水合酶测定确定新的极性衍生物对四种hCA同工型I、II、IV和IX的抑制活性。一些化合物显示出纳摩尔范围内的效力和抑制 hCA IX 的偏好。

  DOI：

  10.1016/j.ejmech.2021.114026

文献信息

• Stereoselective synthesis of conformationally restricted KOR agonists based on the 2,5-diazabicyclo[2.2.2]octane scaffold
  作者：Christian Wittig、Dirk Schepmann、Michael Soeberdt、Constantin G. Daniliuc、Bernhard Wünsch

  DOI：10.1039/c7ob01530e

  日期：——

  the KOR affinity depends on the dihedral angle of the ethylenediamine pharmacophore. Herein, 2,5-diazabicyclooctanes bearing a pyrrolidino moiety in the 7-position were envisaged to study KOR agonists with a conformationally rigid ethylenediamine pharmacophore and thus a defined N(pyrrolidine)–C7–C1–N2 dihedral angle. The first approach with an intramolecular addition at the chiral sulfinylimines 9 failed

  据推测，KOR亲和力取决于乙二胺药效基团的二面角。在此，设想在7位上带有吡咯烷酮部分的2,5-二氮杂双环辛烷研究带有构象刚性乙二胺药效团并因此具有确定的N（吡咯烷）-C7-C1-N2二面角的KOR激动剂。在手性亚磺胺类化合物9上分子内添加的第一种方法未能得到双环产物。第二种方法的关键步骤是Dieckmann类似环化，提供了混合的甲基甲硅烷基缩酮11a-e作为关键中间体。最高KOR亲和力被发现的2,5-二苄基取代的衍生物（小号，- [R ，小号） - 16A（K i = 31 nM）和（R，S，R）-16a（K i = 74 nM），吡咯烷环朝向N-5方向。的高KOR亲和力（小号，- [R ，小号） - 16A是出乎意料的，因为KOR药效乙二胺系统采用约160°的二面角°，这是从柔性的和有效的能量最有利的构象异构体的角度相当不同KOR激动剂2。（S，R，S）-16a代表KOR激动剂，对MOR
• 2-(2-Hydroxyethyl)piperazine derivatives as potent human carbonic anhydrase inhibitors: Synthesis, enzyme inhibition, computational studies and antiglaucoma activity
  作者：Niccolò Chiaramonte、Andrea Angeli、Silvia Sgambellone、Alessandro Bonardi、Alessio Nocentini、Gianluca Bartolucci、Laura Braconi、Silvia Dei、Laura Lucarini、Elisabetta Teodori、Paola Gratteri、Bernhard Wünsch、Claudiu T. Supuran、Maria Novella Romanelli

  DOI：10.1016/j.ejmech.2021.114026

  日期：2022.1

  Targeting Carbonic Anhydrases (CAs) represents a strategy to treat several diseases, from glaucoma to cancer. To widen the structure-activity relationships (SARs) of our series of piperazines endowed with potent human carbonic anhydrase (hCA) inhibition, a new series of chiral piperazines carrying a (2-hydroxyethyl) group was prepared. The Zn-binding function, the 4-sulfamoylbenzoyl moiety, was connected

  靶向碳酸酐酶 (CA) 代表了一种治疗从青光眼到癌症的多种疾病的策略。为了拓宽我们的系列哌嗪的构效关系 (SAR)，这些哌嗪具有有效的人碳酸酐酶 (hCA) 抑制作用，制备了一系列带有 (2-羟乙基) 基团的新手性哌嗪。Zn 结合功能，即 4-氨磺酰基苯甲酰基部分，与一个哌嗪 N 原子相连，而另一个氮被烷基取代基修饰。与用于合成先前报道的系列的方法类似，新化合物的制备从 ( R )- 和 ( S）-天冬氨酸。在合成过程中发生了部分外消旋化。为了克服这个问题，研究了其他化学策略。使用停流CO 2水合酶测定确定新的极性衍生物对四种hCA同工型I、II、IV和IX的抑制活性。一些化合物显示出纳摩尔范围内的效力和抑制 hCA IX 的偏好。
• Synthesis, Pharmacological Evaluation, and σ₁ Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines
  作者：Frauke Weber、Stefanie Brune、Katharina Korpis、Patrick J. Bednarski、Erik Laurini、Valentina Dal Col、Sabrina Pricl、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1021/jm401707t

  日期：2014.4.10

  Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. sigma receptor affinity was recorded using receptor material from both animal and human origin, sigma(1) affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yliethanol (7c) revealed the highest affinity at human sigma(1) receptors (K-i = 6.8 nM). The potent a, receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the a, receptor was analyzed in detail using the 3D homology model of the sigma(1) receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human a, receptor.