(R)-1-(4-fluorobenzyl)-3-methylpiperazine | 422270-29-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-(4-fluorobenzyl)-3-methylpiperazine
• 英文别名: (3R)-1-[(4-fluorophenyl)methyl]-3-methylpiperazine
• CAS: 422270-29-9
• 化学式: C₁₂H₁₇FN₂
• 分子量: 208.279
• InChiKey: NPIPCQHHNIFPQW-SNVBAGLBSA-N

物化性质

• 沸点：
  286.8±25.0 °C(Predicted)
• 密度：
  1.062±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  室温、密封保存，并确保环境干燥。

反应信息

• 作为反应物：
  描述：

  (R)-1-(4-fluorobenzyl)-3-methylpiperazine 在 potassium carbonate 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-3-(2-(2-(4-(4-fluorobenzyl)-2-methylpiperazin-1-yl)-2-oxoethoxy)-5-chlorophenylamino)-4-(2-methoxyethylamino)cyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  Structure–activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists

  摘要：

  Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCRI antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.104
• 作为产物：
  描述：

  (R)-(-)-2-甲基哌嗪 、 对氟苯甲醛 在 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 以86%的产率得到(R)-1-(4-fluorobenzyl)-3-methylpiperazine
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel 2-methylpiperazine derivatives as potent CCR5 antagonists

  摘要：

  Three series of novel 2-methylpiperazine derivatives were designed and synthesized using a fragment-assembly strategy. Among them, six compounds (13, 16, 18, 22, 33, and 36) showed potent activity against CCR5 comparable to that of the positive control, maraviroc, in calcium mobilization assay. Moreover, some compounds were selected and further tested for their antiviral activity in HIV-1 single cycle assay. As a result, four compounds (13, 16, 33, and 36) showed antiviral activity at the nanomolar level. Additionally, the potent four compounds showed no cytotoxicity at a concentration of 10 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.052

文献信息

• [EN] AUTOTAXIN INHIBITORS COMPRISING A HETEROAROMATIC RING-BENZYL-AMIDE-CYCLE CORE<br/>[FR] INHIBITEURS DE L'AUTOTAXINE CONTENANT UN NOYAU À CYCLE BENZYLE-AMIDE CYCLIQUE HÉTÉROAROMATIQUE
  申请人：NOVARTIS AG

  公开号：WO2015008230A1

  公开（公告）日：2015-01-22

  The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.

  本发明涉及新型化合物，这些化合物是自体磷脂酶抑制剂，涉及它们的制备方法，含有它们的药物组合物和药物，以及它们在由自体磷脂酶介导的疾病和紊乱中的应用。
• NOVEL BENZODIOXANE AND BENZOXAZINE DERIVATIVES USEFUL AS CC CHEMOKINE RECEPTOR LIGANDS
  申请人：KHAMRAI Uttam

  公开号：US20100152160A1

  公开（公告）日：2010-06-17

  The present invention relates to benzodioxane and benzoxazine derivatives that act as ligands for CC chemokine receptors, such as CCR1. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.

  本发明涉及作为CC化学趋化因子受体（如CCR1）配体的苯二氧杂环己烷和苯并噁嗪衍生物。该发明还涉及制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。
• Methods of using piperazine derivatives
  申请人：Pfizer Inc

  公开号：US20040092529A1

  公开（公告）日：2004-05-13

  The present invention relates to compounds of the formula I 1 and the pharmaceutically acceptable forms thereof; wherein X, Y, a, b, c, d, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Moreover, the present invention is also directed at pharmaceutical compositions comprising a compound of the formula I and a pharmaceutically acceptable carrier. Furthermore, the present invention is directed at methods of using the herein described compounds and compositions for treating or preventing a disorder or condition that can be treated or prevented by antagonizing the CCR1 receptor in a mammal.

  本发明涉及公式I1的化合物及其药学上可接受的形式；其中X、Y、a、b、c、d、R1、R2、R3、R4和R5如本文所定义。此外，本发明还涉及包含公式I的化合物和药学上可接受的载体的药物组合物。此外，本发明还涉及使用本文所述的化合物和组合物治疗或预防哺乳动物中可通过拮抗CCR1受体治疗或预防的疾病或状况的方法。
• Indole-type derivatives as inhibitors of p38 kinase
  申请人：——

  公开号：US20040142940A1

  公开（公告）日：2004-07-22

  The invention is directed to methods to inhibit p38-&agr; kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.

  该发明涉及使用含有苯基或噻吩基通过哌啶或哌嗪核与吲哚残基相连的化合物来抑制p38-α激酶的方法，其中吲哚残基上强制地具有环氮上的氨基或取代氨基基团。
• Development of autotaxin inhibitors: A series of tetrazole cinnamides
  作者：Christopher G. Thomson、Darren Le Grand、Mark Dowling、David Beattie、Lucy Elphick、Michael Faller、Mark Freeman、Elizabeth Hardaker、Victoria Head、Rene Hemmig、Johan Hill、Andrew Lister、David Pascoe、Sebastien Rieffel、Binesh Shrestha、Oliver Steward、Florence Zink

  DOI：10.1016/j.bmcl.2020.127663

  日期：2021.1

  A series of inhibitors of Autotaxin (ATX) have been developed from a high throughput screening hit, 1a, which shows an alternative binding mode to known catalytic site inhibitors. Selectivity over the hERG channel and microsomal clearance were dependent on the lipophilicity of the compounds, and this was optimised by reduction of clogD whilst maintaining high affinity ATX inhibition. Compound 15a shows

  已从高通量筛选结果1a中开发了一系列自分泌运动抑制因子（ATX），它显示了与已知催化部位抑制剂的另一种结合方式。在hERG通道上的选择性和微粒体清除率取决于化合物的亲脂性，这通过降低clogD来优化，同时保持了高亲和力ATX抑制。如药代动力学-药效学（PK / PD）实验所示，化合物15a表现出良好的口服暴露以及体内LPA形成的浓度依赖性抑制。