(5S)-5-({7-[(2-bromophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl}carbonyl)-1-[(4-methylphenyl)methyl]pyrrolidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (5S)-5-({7-[(2-bromophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl}carbonyl)-1-[(4-methylphenyl)methyl]pyrrolidin-2-one
• 英文别名: (5S)-5-(7-(2-bromobenzyl)-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(4-methylbenzyl)pyrrolidin-2-one；(5S)-5-[7-[(2-bromophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]-1-[(4-methylphenyl)methyl]pyrrolidin-2-one
• 化学式: C₂₇H₃₂BrN₃O₂
• 分子量: 510.474
• InChiKey: WGCFEDQBJXWEDJ-OWWUNANSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (5S)-5-(3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(4-methylbenzyl)pyrrolidin-2-one 、 2-溴溴苄 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以64%的产率得到(5S)-5-({7-[(2-bromophenyl)methyl]-3,7-diazabicyclo[3.3.1]nonan-3-yl}carbonyl)-1-[(4-methylphenyl)methyl]pyrrolidin-2-one
  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

• [EN] 3,7-DIAZABICYCLO[3.3.1 ]NONANE CARBOXAMIDES AS ANTITHROMBOTIC AGENTS<br/>[FR] CARBOXAMIDES DE 3,7-DIAZABICYCLO[3.3.1]NONANE À TITRE D'AGENTS ANTITHROMBOTIQUES
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2015044951A1

  公开（公告）日：2015-04-02

  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. General formula (1) 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。本发明还涉及具有抗血栓（抗血小板）活性的一般式（1）化合物。该发明还涉及将这些基团用作体外和体内介导的胶原受体抑制剂，抑制胶原诱导的血小板粘附和聚集。此外，该发明还涉及这类化合物通过双重机制表现出抗血小板功效，既抑制了胶原又抑制了U46619（血栓素受体激动剂）诱导的血小板聚集。一般式（1）中，其中，R'为；其中R选自烷基、酰基、对甲苯磺酰基、叔丁氧羰基、芳基烷基或取代芳基烷基；R''优选选自卤素、氰基、低烷基、芳基、取代芳基和对甲苯磺基；R1选自氢和低烷基；R2选自低烷基和芳基；R3选自叔丁氧羰基和苯甲氧羰基；n = 0,1。
• 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 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。