L-Proline, 1-((2,6-dichlorophenyl)methyl)-5-oxo-, methyl ester | 59749-20-1

• 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: L-Proline, 1-((2,6-dichlorophenyl)methyl)-5-oxo-, methyl ester
• 英文别名: methyl (2S)-1-[(2,6-dichlorophenyl)methyl]-5-oxopyrrolidine-2-carboxylate
• CAS: 59749-20-1
• 化学式: C₁₃H₁₃Cl₂NO₃
• 分子量: 302.157
• InChiKey: COJJNIMKYLDCCA-NSHDSACASA-N

物化性质

• 密度：
  1.3878 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  L-Proline, 1-((2,6-dichlorophenyl)methyl)-5-oxo-, methyl ester 在 水 、 sodium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.59h， 生成 tert-butyl ((R)-1-((S)-1-(2,6-dichlorobenzyl)-5-oxopyrrolidine-2-carbonyl)piperidin-3-yl)methylcarbamate
  参考文献：
  名称：

  Synthesis and identification of chiral aminomethylpiperidine carboxamides as inhibitor of collagen induced platelet activation

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.05.017
• 作为产物：
  描述：

  2,6-二氯苄基溴 、 L-焦谷氨酸甲酯 在 lithium hexamethyldisilazane 作用下， 生成 L-Proline, 1-((2,6-dichlorophenyl)methyl)-5-oxo-, methyl ester
  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.
• Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids
  作者：Ankita Misra、K.S. Anil Kumar、Manish Jain、Kirti Bajaj、Shyamali Shandilya、Smriti Srivastava、Pankaj Shukla、Manoj K. Barthwal、Madhu Dikshit、Dinesh K. Dikshit

  DOI：10.1016/j.ejmech.2016.01.019

  日期：2016.3

  N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular

  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。