methyl 2S-N-(p-methylphenylmethyl)pyroglutamate | 87341-35-3

• 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: methyl 2S-N-(p-methylphenylmethyl)pyroglutamate
• 英文别名: methyl (2S)-1-[(4-methylphenyl)methyl]-5-oxopyrrolidine-2-carboxylate
• CAS: 87341-35-3
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: PNTBCXNPBFYSEG-LBPRGKRZSA-N

物化性质

• 沸点：
  410.4±45.0 °C(Predicted)
• 密度：
  1.186±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：
  4
• 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：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2S-N-(p-methylphenylmethyl)pyroglutamate 在 水 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以42%的产率得到(2S)-N-(4-methylbenzyl) pyroglutamic acid
  参考文献：
  名称：

  [EN] CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYL- AMINOMETHYL)]-PIPERIDIN-1-YL}-PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  [FR] 1-(4-MÉTHYLPHÉNYLMÉTHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYLAMINOMÉTHYL)]-

  摘要：

  手性l-(4-甲基苯甲基)-5-氧-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺作为胶原诱导的血小板活化和粘附的抑制剂。本发明提供手性(2S)-l-(4-甲基苯甲基)-5-氧-(3S)-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺和(2S)-1-(4-甲基苯甲基)-5-氧-(3R)-{N-[(3-t-丁氧羰基氨甲基)]-哌啶-1-基}-吡咯烷-2-羧酰胺，分别为公式6和7。本发明还涉及使用这些分子作为通过胶原受体介导的胶原诱导的血小板粘附和聚集的抑制剂。本发明提供了一种制备公式6和7的手性羧酰胺的方法，该方法具有避免在N-烷基化过程中α-羧基中发生任何消旋的优点。在低温下使用试剂LiHMDS可提供良好的手性纯度的甲基N-(对甲基苯甲基)吡咯酰胺。

  公开号：

  WO2012104866A1
• 作为产物：
  描述：

  4-甲基苄溴 、 L-焦谷氨酸甲酯 在 lithium hexamethyldisilazane 作用下， 生成 methyl 2S-N-(p-methylphenylmethyl)pyroglutamate
  参考文献：
  名称：

  N-取代的焦谷氨酸双spidine衍生物的双重抗血小板活性的合成和评价

  摘要：

  制备了取代的联吡啶的N-芳烷基焦谷氨酰胺，并在体内和体外评估其抑制胶原诱导的血小板聚集的能力。一些化合物显示出很高的抗血小板功效（体外），其中有六种化合物通过双重机制抑制胶原蛋白以及U46619诱导的血小板凝集，并具有浓度依赖性的抗血小板功效。特别地，该化合物4 Ĵ提供针对显著保护胶原诱导肾上腺素肺血栓栓塞症，以及氯化铁诱导的动脉血栓形成，而不影响在小鼠出血倾向。因此，本研究表明化合物4 j 显示出显着的抗血栓形成功效，比阿司匹林和氯吡格雷好得多。

  DOI：

  10.1016/j.ejmech.2016.01.019

文献信息

• Synthesis and identification of chiral aminomethylpiperidine carboxamides as inhibitor of collagen induced platelet activation
  作者：K.S. Anil Kumar、Ankita Misra、Tanveer Irshad Siddiqi、Stuti Srivastava、Manish Jain、Rabi Sankar Bhatta、Manoj Barthwal、Madhu Dikshit、Dinesh K. Dikshit

  DOI：10.1016/j.ejmech.2014.05.017

  日期：2014.6

  A series of chiral lactam carboxamides of aminomethylpiperidine were synthesized and investigated for the collagen induced in vitro anti-platelet efficacy and collagen plus epinephrine induced in vivo pulmonary thromboembolism. The compound 31a (30 mu M/kg) displayed a remarkable antithrombotic efficacy (60% protection) which was sustained for more than 24 h and points to its excellent bioavailability. The compounds 31a (IC50 = 6.6 mu M) and 32a (IC50 = 37 mu M), as well as their racemic mixture 28i (IC50 = 16 mu M) significantly inhibited collagen-induced human platelet aggregation in vitro. Compound 34c displayed dual mechanism of action against both collagen (IC50 = 3.3 mu M) and U46619 (IC50 = 2.7 mu M) induced platelet aggregation. The pharmacokinetic study of 31a indicated very faster absorption, prolonged and constant systemic exposure and thereby exhibiting better therapeutic response. (C) 2014 Elsevier Masson SAS. All rights reserved.
• CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYL-AMINOMETHYL)]-PIPERIDIN-1-YL}-PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  申请人：Council of Scientific & Industrial Research

  公开号：EP2670722A1

  公开（公告）日：2013-12-11
• CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO--PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION
  申请人：Council of Scientific & Industrial Research

  公开号：US20160143896A1

  公开（公告）日：2016-05-26

  Chiral 1-(4-methylphenylmethyl)-5-oxo-N-[(3-t-butoxycarbonyl-aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamides as inhibitors of collagen induced platelet activation and adhesion. The present invention provides chiral (2S)-1-(4-methyl-phenylmethyl)-5-oxo-(3S)-N-[(3-t-butoxycarbonyl aminomethyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide, and (2S)-1-(4-methylphenylmethyl)-5-oxo-(3R)-N-[(3-t-butoxycarbonyl amino methyl)]-piperidin-1-yl}-pyrrolidine-2-carboxamide of formula 6 and 7 respectively. The present invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors. The present invention provides a process for preparation of chiral carboxamides of formula 6 and 7 using the process which has advantage to avoid any racemization at the a-carboxylic center, during N-alkylation. The reagent LiHMDS is used at low temperatures to furnish methyl N-(p-methylphenylmethyl)1pyroglutamate in good chiral purity.
• US9206155B2
  申请人：——

  公开号：US9206155B2

  公开（公告）日：2015-12-08
• US9687480B2
  申请人：——

  公开号：US9687480B2

  公开（公告）日：2017-06-27