(2R,4R)-4-amino-1-benzyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester | 911697-25-1

• 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: (2R,4R)-4-amino-1-benzyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester
• 英文别名: dimethyl (2R,4R)-4-amino-1-benzylpyrrolidine-2,4-dicarboxylate
• CAS: 911697-25-1
• 化学式: C₁₅H₂₀N₂O₄
• 分子量: 292.335
• InChiKey: GERUWGIJRXNVCE-IUODEOHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4R)-4-amino-1-benzyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester 在 palladium dihydroxide 盐酸 、 N-氯代丁二酰亚胺 、 titanium(III) chloride 、 苄基三乙基氯化铵 、 氨 、 氢气 、 碳酸氢钠 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 11.0h， 生成 1-amino-APDC
  参考文献：
  名称：

  1-amino-APDC, a partial agonist of group II metabotropic glutamate receptors with neuroprotective properties

  摘要：

  The synthesis of the 1-amino derivative of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid (1-amino-APDC), a selective metabotropic glutamate ligand, is disclosed. This compound acts as a partial agonist of the group II mGluRs and shows pronounced neuroprotective properties in the NMDA model of cell toxicity, (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00266-8
• 作为产物：
  描述：

  ethyl (8R)-7-benzyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonane-8-carboxylate 在 sodium hydroxide 、 氯化亚砜 作用下， 生成 (2R,4R)-4-amino-1-benzyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester
  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

文献信息

• Trans Pyrrolidinyl Derivates and Their Pharmaceutical Use
  申请人：Schann Stephan

  公开号：US20080027127A1

  公开（公告）日：2008-01-31

  The present invention relates to the use of trans pyrrolidinyl of the formula (I) or (II) in which: R 1 , R 2 or R 3 are hydrogen or a carboxy or amino protecting group; R 4 to R 8 represent hydrogen or an alkyl radical; R 9 represents a (R 10 ) n (—R 11 ) m group wherein R 10 is —CO—, —CS—, —O—, —S—, —SO—, —SO 2 —, —COO—, —CONR a —, —N(R a )CO—, —CSNR a —, —N(R a )CS—, —N(R a )—, R b , aryl, and R 11 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）的反式吡咯烷基，其中：R1、R2或R3为氢或羧基或氨基保护基；R4至R8表示氢或烷基基团；R9表示（R10）n（—R11）m基团，其中R10为—CO—、—CS—、—O—、—S—、—SO—、—SO2—、—COO—、—CONRa—、—N（Ra）CO—、—CSNRa—、—N（Ra）CS—、—N（Ra）—、Rb、芳基，而R11为极性基团，用于治疗和/或预防与改变谷氨酸能信号和/或功能相关的疾病和/或可以受到哺乳动物谷氨酸水平或信号改变影响的疾病。
• Design and synthesis of APTCs (aminopyrrolidinetricarboxylic acids): Identification of a new group III metabotropic glutamate receptor selective agonist
  作者：Stephan Schann、Christel Menet、Paul Arvault、Géraldine Mercier、Mélanie Frauli、Stanislas Mayer、Nadia Hubert、Nicolas Triballeau、Hugues-Olivier Bertrand、Francine Acher、Pascal Neuville

  DOI：10.1016/j.bmcl.2006.06.062

  日期：2006.9

  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.
• 1-amino-APDC, a partial agonist of group II metabotropic glutamate receptors with neuroprotective properties
  作者：Alan P Kozikowski、Gian Luca Araldi、Werner Tückmantel、Sergey Pshenichkin、Elena Surina、Jarda T Wroblewski

  DOI：10.1016/s0960-894x(99)00266-8

  日期：1999.6

  The synthesis of the 1-amino derivative of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid (1-amino-APDC), a selective metabotropic glutamate ligand, is disclosed. This compound acts as a partial agonist of the group II mGluRs and shows pronounced neuroprotective properties in the NMDA model of cell toxicity, (C) 1999 Elsevier Science Ltd. All rights reserved.