ethyl (2S,4R)-1-benzyl-4-hydroxyprolinate | 154342-88-8

• 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,4R)-1-benzyl-4-hydroxyprolinate
• 英文别名: (2S,4R)-1-Benzyl-4-hydroxy-pyrrolidine-2-carboxylic acid ethyl ester；ethyl (2S,4R)-1-benzyl-4-hydroxypyrrolidine-2-carboxylate
• CAS: 154342-88-8
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: MZCRIMVOOXQIAJ-OLZOCXBDSA-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：

  ethyl (2S,4R)-1-benzyl-4-hydroxyprolinate 在 4-二甲氨基吡啶 、 锂硼氢 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 (2S,4S)-1-benzyl-2-<(tert-butyldimethylsilyloxy)methyl>pyrrolidine-4-spiro-5'-hydantoin
  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
• 作为产物：
  描述：

  L-羟基脯氨酸 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 ethyl (2S,4R)-1-benzyl-4-hydroxyprolinate
  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] TRICYCLIC COMPOUNDS AS HISTONE METHYL-TRANSFERASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASES
  申请人：GLOBAL BLOOD THERAPEUTICS INC

  公开号：WO2019036377A1

  公开（公告）日：2019-02-21

  The present disclosure provides certain tricyclic compounds that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinopathies (e.g., beta-thalassemia and sickle cell disease). Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本公开提供了某些三环化合物，它们是组蛋白甲基转移酶G9a和/或GLP抑制剂，因此可用于治疗通过抑制G9a和/或GLP可治疗的疾病，如癌症和血红蛋白病（例如β地中海贫血和镰状细胞病）。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• [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。
• 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.