ethyl (2S)-1-benzyl-4-oxoprolinate | 154342-89-9

• 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: ethyl (2S)-1-benzyl-4-oxoprolinate
• 英文别名: (2S)-ethyl N¹-benzyl-4-oxopyrrolidine-2-carboxylate；(S)-1-benzyl-4-oxopyrrolidine-2-carboxylic acid ethyl ester；ethyl (2S)-1-benzyl-4-oxopyrrolidine-2-carboxylate
• CAS: 154342-89-9
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: LXJNWJIUSCLOIV-ZDUSSCGKSA-N

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：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (2S)-1-benzyl-4-oxoprolinate 在 sodium hydroxide 、 氯化亚砜 作用下， 以 乙醇 、 水 为溶剂， 生成 methyl (2S,4R)-4-amino-1-benzyl-4-methoxycarbonylprolinate
  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：

  (4R)-4-羟基-L-脯氨酸盐酸盐 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 ethyl (2S)-1-benzyl-4-oxoprolinate
  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] 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。
• 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。
• Synthesis of the Four Isomers of 4-Aminopyrrolidine-2,4-dicarboxylate:  Identification of a Potent, Highly Selective, and Systemically-Active Agonist for Metabotropic Glutamate Receptors Negatively Coupled to Adenylate Cyclase
  作者：James A. Monn、Matthew J. Valli、Bryan G. Johnson、Craig R. Salhoff、Rebecca A. Wright、Trevor Howe、Ann Bond、David Lodge、Larry A. Spangle、Jonathan W. Paschal、Jack B. Campbell、Kelly Griffey、Joseph P. Tizzano、Darryle D. Schoepp

  DOI：10.1021/jm9601765

  日期：1996.1.1

  The four isomers of 4-aminopyrrolidine-2,4-dicarboxylate (APDC) were prepared and evaluated for their effects at glutamate receptors in vitro. (2R,4R)-APDC (2a), an aza analog of the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD, 1), was found to possess relatively high affinity for metabotropic glutamate receptors (mGluRs) (ACPD-sensitive [H-3]glutamate binding IC50 = 6.49 +/- 1.21 mu M) with no effects on radioligand binding to NMDA, AMPA, or kainate receptors up to 100 mu M. None of the other APDC isomers showed significant mGluR binding affinity, indicating that this interaction is highly stereospecific. Both 1 and 2a were effective in decreasing forskolin-stimulated cAMP formation in the adult rat cerebral cortex (EC(50) = 8.17 +/- 2.21 mu M for 1; EC(50) = 14.51 +/- 5.54 mu M for 2a); however, while 1 was also effective in stimulating basal tritiated inositol monophosphate production in the neonatal rat cerebral cortex (EC(50) = 27.7 +/- 5.2 mu M), 2a (up to 100 mu M) was ineffective in stimulating phosphoinositide hydrolysis in this tissue preparation, further supporting our previous observations that 2a is a highly selective agonist for mGluRs negatively coupled to adenylate cyclase. Microelectrophoretic application of either 1 or 2a to intact rat spinal neurons produced an augmentation of AMPA-induced excitation (95 +/- 10% increase for 1, 52 +/- 6% increase for 2a). Intracerebral injection of 1 (400 nmol) produced characteristic limbic seizures in mice which are not mimicked by 2a (200-1600 nmol, ic). However, the limbic seizures induced by 1 were blocked by systemically administered 2a in a dose-dependent manner (EC(50) = 271 mg/kg, ip). It is concluded that (2R,4R)-APDC (2a) is a highly selective, systemically-active agonist of mGluRs negatively coupled to adenylate cyclase and that selective activation of these receptors in vivo can result in anticonvulsant effects.
• CIS PYRROLIDINYL DERIVATIVES AND THEIR USES
  申请人：Faust Pharmaceuticals

  公开号：EP1751099A1

  公开（公告）日：2007-02-14
• [EN] CIS PYRROLIDINYL DERIVATIVES AND THEIR USES<br/>[FR] DERIVES DE CIS PYRROLIDINYLE ET LEURS UTILISATIONS
  申请人：FAUST PHARMACEUTICALS

  公开号：WO2005118534A1

  公开（公告）日：2005-12-15

  The present invention provides new cis 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, and their use for the treatment and/or prophylaxis of a condition associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling.