(2R,4R)-ethyl N¹-benzyl-4-hydroxypyrrolidine-2-carboxylate | 171192-72-6

• 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,4R)-ethyl N¹-benzyl-4-hydroxypyrrolidine-2-carboxylate
• 英文别名: ethyl (2R,4R)-1-benzyl-4-hydroxypyrrolidine-2-carboxylate；ethyl (2R,4R)-1-benzyl-4-hydroxyprolinate；(2R,4R)-1-benzyl-4-hydroxy-pyrrolidine-2-carboxylic acid ethyl ester；(2R,4R) ethyl-1-benzyl-4-hydroxypyrrolidine-2-carboxylate
• CAS: 171192-72-6
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: MZCRIMVOOXQIAJ-CHWSQXEVSA-N

物化性质

• 沸点：
  364.2±42.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4R)-ethyl N¹-benzyl-4-hydroxypyrrolidine-2-carboxylate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 ethyl (8R)-7-benzyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonane-8-carboxylate
  参考文献：
  名称：

  Design and synthesis of APTCs (aminopyrrolidinetricarboxylic acids): Identification of a new group III metabotropic glutamate receptor selective agonist

  摘要：

  A new family of mGlu receptor orthosteric ligands called APTCs was designed and synthesized using a parallel chemistry approach. Amongst 65 molecules tested on mGlu4, mGlu6 and mGlu8 subtypes, (2S,4S)-4-amino-1-[(E)-3-carboxyacryloyl]pyrrolidine-2,4-dicarboxylic acid (8a06-FP0429) has been shown to be a full mGlu4 agonist and a partial mGlu8 agonist. In addition, 8a06 was shown to be selective versus group I and II mGlu subtypes. A possible explanation for this efficacy difference is proposed by docking experiment performed with molecular model of the receptor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.062
• 作为产物：
  描述：

  顺式-4-羟基-D-脯氨酸盐酸盐 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 (2R,4R)-ethyl N¹-benzyl-4-hydroxypyrrolidine-2-carboxylate
  参考文献：
  名称：

  Asymmetric syntheses of all four isomers of 4-amino-4-carboxyproline: Novel conformationally restricted glutamic acid analogues

  摘要：

  Asymmetric syntheses of all four isomers of 4-amino-4-carboxyprolines, i.e. (2S,4S)-3, (2S,4R)-4, and their corresponding enantiomers, as novel conformationally restricted analogues of glutamic acid, were performed from trans-4-hydroxy-L-proline as a homochiral starting material. The key step was the spirohydantoin ring formation by employing the Bucherer-Bergs reaction of 4-oxoproline derivatives. These structures were determined by NMR studies.

  DOI：

  10.1016/0957-4166(95)00209-8

文献信息

• [EN] MODULATORS OF CELLULAR ADHESION<br/>[FR] MODULATEURS DE L'ADHESION CELLULAIRE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2005044817A1

  公开（公告）日：2005-05-19

  The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1-R4, n, p, A, B, D, E, L and AR1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).

  本发明提供具有以下式（I）的化合物及其药学上可接受的衍生物，其中R1-R4、n、p、A、B、D、E、L和AR1如本文中一般描述的那样，并且另外提供这些药物组合物以及用于治疗由CD11/CD18细胞粘附分子家族介导的疾病（例如LFA-1）的使用方法。
• Pyrrolidinyl di-carboxylic acid derivatives as metabotropic glutamate
  申请人：Eli Lilly and Company

  公开号：US05473077A1

  公开（公告）日：1995-12-05

  The present invention provides novel compounds that affect certain excitatory amino acid receptors, and are useful in the treatment of neurological disorders and psychiatric disorders.

  本发明提供了影响某些兴奋性氨基酸受体的新化合物，可用于治疗神经系统疾病和精神疾病。
• Pyrrolidinyl di-carboxylic acid derivatives as metabotropic glutamate receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0703218A1

  公开（公告）日：1996-03-27

  The present invention provides pyrrolidinyl di-carboxylic acid derivatives that affect certain excitatory amino acid receptors, and are useful in the treatment of neurological disorders and psychiatric disorders. This invention further provides novel pyrrolidinyl di-carboxylic acid derivatives and pharmaceutical formulations employing these novel compounds.

  本发明提供了影响特定兴奋性氨基酸受体的吡咯烷二羧酸衍生物，并且在治疗神经系统疾病和精神疾病方面具有用途。本发明还提供了新型的吡咯烷二羧酸衍生物和使用这些新化合物的药物配方。
• [EN] TRANS PYRROLIDINYL DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES DE TRANS PYRROLIDINYLE ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：FAUST PHARMACEUTICALS

  公开号：WO2005118533A1

  公开（公告）日：2005-12-15

  The present invention relates to the use of trans pyrrolidinyl of the formula (I) or (II) in which: R1, R2 or R3 are hydrogen or a carboxy or amino protecting group; R4 to R8 represent hydrogen or an alkyl radical; R9 represents a (R10)n(-R11)m group wherein R10 is -CO-, -CS-, -O-, -S-, -SO-, -SO2-, -COO-, -CONRa-, -N(Ra)CO-, -CSNRa-, -N(Ra)CS-, -N(Ra)-, Rb, aryl, and R11 is a polar group, for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals.

  本发明涉及使用式（I）或（II）的trans吡咯烷基，其中：R1、R2或R3是氢或羧基或氨基保护基；R4至R8代表氢或烷基基团；R9代表（R10）n（-R11）m基团，其中R10是-CO-、-CS-、-O-、-S-、-SO-、-SO2-、-COO-、-CONRa-、-N(Ra)CO-、-CSNRa-、-N(Ra)CS-、-N(Ra)-、Rb、芳基，R11是一个极性基团，用于治疗和/或预防与改变谷氨酸能信号和/或功能有关的疾病，以及可以通过改变哺乳动物体内谷氨酸水平或信号传导而受影响的疾病。
• Enantiospecific synthesis and receptor binding of novel dopamine receptor ligands employing natural 4-hydroxyproline as a practical and flexible building block
  作者：Cornelia Heindl、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.tetasy.2003.08.020

  日期：2003.10

  Starting from natural 4-hydroxyproline, an ex-chiral pool approach is described giving access to 2-aminoalkylpyrrolidine derivatives that were used as chiral building blocks for the synthesis of bioactive 2-methoxybenzamide derivatives. The 4-hydroxy substituent can be displaced employing organocuprates as useful carbanion equivalents. Dopamine and serotonin binding studies involving the subtypes D1

  从天然的4-羟基脯氨酸开始，描述了一种手性前池方法，该方法可得到2-氨基烷基吡咯烷衍生物，该衍生物用作合成生物活性2-甲氧基苯甲酰胺衍生物的手性构件。可以使用有机铜酸盐作为有用的碳负当量置换4-羟基取代基。多巴胺和涉及亚型D1，D2血清素结合研究长，D2短，D3和D4，以及5-HT1甲和5-HT2，分别提供有趣的见解立体结构活性关系。（2 S，4 R）-2-氨基甲基吡咯烷衍生物ent -66和（2 R，4 S）-2-氨基乙基吡咯烷衍生物68分别显示出对多巴胺D3和D4受体亚型的显着亲和力和偏爱性，两者都被认为与精神分裂症的症状有关。