N,N'-(1,4-phenylenebis(methylene))bis(N-methylaniline)

• 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: N,N'-(1,4-phenylenebis(methylene))bis(N-methylaniline)
• 英文别名: MSX-164；US9205085, Msx-164；N-methyl-N-[[4-[(N-methylanilino)methyl]phenyl]methyl]aniline
• 化学式: C₂₂H₂₄N₂
• 分子量: 316.446
• InChiKey: VPCPAFURUMVILF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对苯二甲醛 、 N-甲基苯胺 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以93%的产率得到N,N'-(1,4-phenylenebis(methylene))bis(N-methylaniline)
  参考文献：
  名称：

  Discovery of Small Molecule CXCR4 Antagonists

  摘要：

  In light of a proposed molecular mechanism for the C-X-C chemokine receptor type 4 (CXCR4) antagonist 1 (AMD3100), a template with the general structure 2 was designed, and 15 was identified as a lead by means of an affinity binding assay against the ligand-mimicking CXCR4 antagonist 3 (TN14003). Following a structure-activity profile around 15, the design and synthesis of a series of novel small molecular CXCR4 antagonists led to the discovery of 32 (WZ811). The compound shows subnanomolar potency (EC50 = 0.3 nM) in an affinity binding assay. In addition, when subjected to in vitro functional evaluation, 32 efficiently inhibits CXCR4/stromal cell-derived factor-1 (SDF-1)-mediated modulation of cyclic adenosine monophophate (CAMP) levels (EC50 = 1.2 nM) and SDF-1 induced Matrigel invasion (EC50 = 5.2 nM). Molecular field topology analysis (MFTA), a 2D quantitative structure-activity relationship (QSAR) approach based on local molecular properties (Van der Waals radii (VdW), atomic charges, and local lipophilicity), applied to the 32 series suggests structural modifications to improve potency.

  DOI：

  10.1021/jm070679i

文献信息

• Methylation of aromatic amines and imines using formic acid over a heterogeneous Pt/C catalyst
  作者：Lei Zhu、Lian-Sheng Wang、Bojie Li、Wei Li、Boqiao Fu

  DOI：10.1039/c6cy00674d

  日期：——

  We describe here a commercially available Pt/C catalyst capable of catalyzing the methylation of anilines and aromatic imines with formic acid in the presence of a hydrosilane reductant. Both primary aniline and secondary aniline can be methylated. The advantage of this newly described method includes operational simplicity, high TON, ready availability of the catalyst, and also good functional group

  我们在此描述了一种在市售的Pt / C催化剂，该催化剂能够在氢化硅烷还原剂的存在下，用甲酸催化苯胺和芳香亚胺的甲基化。伯苯胺和仲苯胺均可被甲基化。该新描述的方法的优点包括操作简单，高TON，催化剂的易得性以及良好的官能团相容性。
• Symmetrical bis-tertiary amines as novel CXCR4 inhibitors
  作者：Renren Bai、Zhongxing Liang、Younghyoun Yoon、Shuangping Liu、Theresa Gaines、Yoonhyeun Oum、Qi Shi、Suazette Reid Mooring、Hyunsuk Shim

  DOI：10.1016/j.ejmech.2016.04.040

  日期：2016.8

  series of novel tertiary amine derivatives targeting CXCR4 were designed, synthesized, and evaluated. The central benzene ring linker and side chains were modified and optimized to study the structure–activity relationship. Seven compounds displayed much more potent activity than the reference drug, AMD3100, in both the binding affinity assay and the blocking of Matrigel invasion functional assay. These

  CXCR4抑制剂是用于治疗癌症转移和炎症的有前途的药物。设计，合成和评估一系列针对CXCR4的新型叔胺衍生物。修饰和优化了中心苯环连接基和侧链，以研究结构与活性之间的关系。在结合亲和力测定和阻断Matrigel侵袭功能测定中，七种化合物的活性均比参比药物AMD3100强得多。与100nM的AMD3100相比，这些化合物在结合亲和力测定法中显示的有效浓度范围为1至100 nM，并且抑制了65.3％至100％的侵袭。化合物IIn在小鼠模型中显示出对角叉菜胶诱导的爪炎症的抑制作用为50％，与肽拮抗剂TN14003（48％）一样有效。这些数据表明，对称的双叔胺是独特的具有高效力的CXCR4抑制剂。
• [EN] TRICYCLIC AMINO CONTAINING COMPOUNDS FOR TREATMENT OR PREVENTION OF SYMPTOMS ASSOCIATED WITH ENDOCRINE DYSFUNCTION<br/>[FR] COMPOSÉS CONTENANT DES ACIDES AMINÉS TRICYCLIQUES POUR LE TRAITEMENT OU LA PRÉVENTION DE SYMPTÔMES ASSOCIÉS À UN DYSFONCTIONNEMENT ENDOCRINIEN
  申请人：UNIV EMORY

  公开号：WO2013070660A1

  公开（公告）日：2013-05-16

  The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.

  本公开提供了使用某些化合物治疗内分泌紊乱的某些症状的方法，特别是与潮热相关的症状的方法。
• Tricyclic amino containing compounds for treatment or prevention of symptoms associated with endocrine dysfunction
  申请人：Emory University

  公开号：US10632120B2

  公开（公告）日：2020-04-28

  The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.

  本公开提供了某些化合物的使用方法，这些化合物可用于治疗内分泌紊乱的某些症状，尤其是与潮热相关的症状。
• TRICYCLIC AMINO CONTAINING COMPOUNDS FOR TREATMENT OR PREVENTION OF SYMPTOMS ASSOCIATED WITH ENDOCRINE DYSFUNCTION
  申请人：Emory University

  公开号：EP2776387B1

  公开（公告）日：2017-02-01