(2S)-1-[(4-bromophenyl)methyl]-5-oxopyrrolidine-2-carboxylic acid | 87341-47-7

• 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: (2S)-1-[(4-bromophenyl)methyl]-5-oxopyrrolidine-2-carboxylic acid
• CAS: 87341-47-7
• 化学式: C₁₂H₁₂BrNO₃
• 分子量: 298.136
• InChiKey: HIHCMWIQHUQLBO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-1-[(4-bromophenyl)methyl]-5-oxopyrrolidine-2-carboxylic acid 在 甲醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-N-(4-((4-((2-aminophenyl)carbamoyl)benzyl)oxy)benzyl)-1-(4-bromobenzyl)-5-oxopyrrolidine-2-carboxamide
  参考文献：
  名称：

  具有抗增殖和抗纤维化活性的 I 类 HDAC 酶的 N-(2-氨基苯基)-苯甲酰胺抑制剂

  摘要：

  组蛋白脱乙酰酶 (HDAC) 抑制剂作为新型抗癌药物受到特别关注。在各类合成抑制剂中，苯甲酰胺类构成了重要的一类，其中一种是已批准的药物（西达本胺）。在这里，我们提出了一类新型 HDAC 抑制剂，其含有N- (2-氨基苯基)-苯甲酰胺功能作为与各种帽基（包括氨基酸焦谷氨酸和脯氨酸）连接的锌结合基团。我们已经鉴定出苯甲酰胺能够在纳摩尔浓度下抑制 HADC1 和 HDAC2，并在微摩尔浓度下对 A549 和 SF268 癌细胞系具有抗增殖活性。对接研究揭示了苯甲酰胺抑制剂与 HDAC1 的结合模式，而细胞分析揭示了EGFR mRNA 和蛋白质的表达下调。在博来霉素诱导的肺纤维化小鼠模型中研究了两种苯甲酰胺，两种苯甲酰胺都显示出对预防性给药方案的功效。I 类 HDAC 的N- (2-氨基苯基)-苯甲酰胺抑制剂可能会带来治疗纤维化疾病的新方法。

  DOI：

  10.1021/acs.jmedchem.3c01422
• 作为产物：
  描述：

  L-焦谷氨酸甲酯 在 水 、 sodium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 10.0h， 生成 (2S)-1-[(4-bromophenyl)methyl]-5-oxopyrrolidine-2-carboxylic acid
  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

文献信息

• Synthesis of novel 2-pyrrolidinone and pyrrolidine derivatives and study of their inhibitory activity against autotaxin enzyme
  作者：Dimitrios Triantafyllos Gerokonstantis、Aikaterini Nikolaou、Christiana Magkrioti、Antreas Afantitis、Vassilis Aidinis、George Kokotos、Panagiota Moutevelis-Minakakis

  DOI：10.1016/j.bmc.2019.115216

  日期：2020.1

  importance. In the present work a novel class of ATX inhibitors, optically active derivatives of 2-pyrrolidinone and pyrrolidine heterocycles were synthesized. Some of them exhibited interesting in vitro activity, namely the hydroxamic acid 16 (IC50 700 nM) and the carboxylic acid 40b (IC50 800 nM), while the boronic acid derivatives 3k (IC50 50 nM), 3l (IC50 120 nM), 3 m (IC50 180 nM) and 21 (IC50 35 nM) were

  自黑素（ATX）是一种从黑素瘤细胞中分离为自分泌运动因子的糖蛋白（〜125 kDa），属于外核苷酸焦磷酸酶/磷酸二酯酶（ENPP）的七元家族，并具有溶血磷脂酶D的活性。ATX负责溶血磷脂酰胆碱（LPC）的水解以产生具有生物活性的脂质溶血磷脂酸（LPA），其在多种病理性炎症条件（包括纤维化，癌症，肝毒性和血栓形成）中被上调。鉴于其在人类疾病中的作用，ATX-LPA轴是一个有趣的治疗靶标，新型有效ATX抑制剂的开发非常重要。在本工作中，合成了新型的ATX抑制剂，2-吡咯烷酮和吡咯烷杂环的光学活性衍生物。
• 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。
• 3,7-DIAZABICYCLO[3.3.1]NONANE CARBOXAMIDES AS ANTITHROMBOTIC AGENTS
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US20160214983A1

  公开（公告）日：2016-07-28

  The present invention relates to the 3,7-diazabicyclo[3.3.1]nonane carboxamides and process for preparation thereof. The present invention further relates to the compounds of general formula 1 possessing anti-thrombotic (anti-platelet) activities. The invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors both in vitro and in vivo. Further, invention also relates these class of compounds exhibiting anti-platelet efficacy through dual mechanism inhibited both collagen as well as U46619 (thromboxane receptor agonist) induced platelet aggregation. wherein, R′ is; wherein R is selected from alkyl, acyl, tosyl, tert-butyloxycarbonyl, araalkyl or substituted araalkyl groups; R″ is selected preferably from halogen, cyano, lower alkyl, aryl, substituted aryl, and tosyl groups; R1 is selected from hydrogen and lower alkyl groups; R2 is selected from lower alkyl and aryl groups; R3 is selected from tert-butyloxycarbonyl and bezyloxycarbonyl groups; n=0,1.

  本发明涉及3,7-二氮杂双环[3.3.1]壬烷羧酰胺及其制备方法。本发明进一步涉及一般式1的化合物，具有抗血栓（抗血小板）活性。发明还涉及使用这些分子作为体外和体内抑制胶原诱导的血小板粘附和聚集介导的胶原受体的抑制剂。此外，发明还涉及这类化合物通过双重机制抑制胶原和U46619（血栓素A2受体激动剂）诱导的血小板聚集，表现出抗血小板功效。其中，R'为；其中，R选择自烷基，酰基，对甲苯磺酰基，叔丁氧羰基，芳基烷基或取代芳基基团；R″优选选择自卤素，氰基，低烷基，芳基，取代芳基和对甲苯磺酰基基团；R1选择自氢和低烷基基团；R2选择自低烷基和芳基基团；R3选择自叔丁氧羰基和苄氧羰基基团；n=0,1。
• 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.
• <i>N</i>-(2-Aminophenyl)-benzamide Inhibitors of Class I HDAC Enzymes with Antiproliferative and Antifibrotic Activity
  作者：Dimitrios Triantafyllos Gerokonstantis、Christiana Mantzourani、Dimitrios Gkikas、Kai-Chen Wu、Huy N. Hoang、Ierasia Triandafillidi、Ilianna Barbayianni、Paraskevi Kanellopoulou、Alexandros C. Kokotos、Panagiota Moutevelis-Minakakis、Vassilis Aidinis、Panagiotis K. Politis、David P. Fairlie、George Kokotos

  DOI：10.1021/acs.jmedchem.3c01422

  日期：2023.10.26

  Inhibitors of histone deacetylases (HDACs) have received special attention as novel anticancer agents. Among various types of synthetic inhibitors, benzamides constitute an important class, and one is an approved drug (chidamide). Here, we present a novel class of HDAC inhibitors containing the N-(2-aminophenyl)-benzamide functionality as the zinc-binding group linked to various cap groups, including

  组蛋白脱乙酰酶 (HDAC) 抑制剂作为新型抗癌药物受到特别关注。在各类合成抑制剂中，苯甲酰胺类构成了重要的一类，其中一种是已批准的药物（西达本胺）。在这里，我们提出了一类新型 HDAC 抑制剂，其含有N- (2-氨基苯基)-苯甲酰胺功能作为与各种帽基（包括氨基酸焦谷氨酸和脯氨酸）连接的锌结合基团。我们已经鉴定出苯甲酰胺能够在纳摩尔浓度下抑制 HADC1 和 HDAC2，并在微摩尔浓度下对 A549 和 SF268 癌细胞系具有抗增殖活性。对接研究揭示了苯甲酰胺抑制剂与 HDAC1 的结合模式，而细胞分析揭示了EGFR mRNA 和蛋白质的表达下调。在博来霉素诱导的肺纤维化小鼠模型中研究了两种苯甲酰胺，两种苯甲酰胺都显示出对预防性给药方案的功效。I 类 HDAC 的N- (2-氨基苯基)-苯甲酰胺抑制剂可能会带来治疗纤维化疾病的新方法。