4,6-bis<4'-<<2''-(dimethylamino)ethyl>thio>phenyl>pyrimidine | 117269-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4,6-bis<4'-<<2''-(dimethylamino)ethyl>thio>phenyl>pyrimidine
• 英文别名: 4,6-bis-[4'-[[2''-(dimethylamino)ethyl]mercapto]phenyl]pyrimidine；4,6-Bis(4'-((2''-(dimethylamino)ethyl)thio)phenyl)pyrimidine；2-[4-[6-[4-[2-(dimethylamino)ethylsulfanyl]phenyl]pyrimidin-4-yl]phenyl]sulfanyl-N,N-dimethylethanamine
• CAS: 117269-54-2
• 化学式: C₂₄H₃₀N₄S₂
• 分子量: 438.661
• InChiKey: ZZPCIWYXMUGILU-UHFFFAOYSA-N

物化性质

• 沸点：
  581.8±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴苯硼酸 在 四(三苯基膦)钯 sodium hydroxide 、 potassium carbonate 、 乙硫醇钠 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 4,6-bis<4'-<<2''-(dimethylamino)ethyl>thio>phenyl>pyrimidine
  参考文献：
  名称：

  Biarylpyrimidines: a new class of ligand for high-order DNA recognitionElectronic supplementary information (ESI) available: experimental details of UV melting studies and example spectroscopic and analytical data. See http://www.rsc.org/suppdata/cc/b3/b301554h/

  摘要：

  具有ω-氨基烷基取代基的联苯嘧啶类化合物已被设计为高阶DNA结构的配体：分光光度法、热学法及竞争平衡透析法检测显示，将取代基连接的功能基团由硫醚改为酰胺，可使其结构结合偏好从三链DNA转变为四链DNA；新型的配体无毒且对人类端粒酶具有中等抑制作用。

  DOI：

  10.1039/b301554h

文献信息

• Binding of unfused aromatic cations to DNA. The influence of molecular twist on intercalation
  作者：W. David. Wilson、Lucjan. Strekowski、Farial A. Tanious、Rebecca A. Watson、Jerzy L. Mokrosz、Alewtina. Strekowska、Gordon D. Webster、Stephen. Neidle

  DOI：10.1021/ja00233a003

  日期：1988.12

  1 (48° versus 25° from MM2) in solution. X-ray crystallographic analysis indicates that the torsional angles are 10° and 19° for the two phenyl-pyrimidine plane intersections in 1. The DNA binding constant for 1 is similar to those for other strong intercalators, and viscometric, flow dichroism, and NMR experiments (nonexchangeable protons of 1, imino proton, and 31P spectra of DNA in the complex) indicate

  一种新型嵌入剂 1 及其非嵌入类似物 2 都围绕连接芳环的扭转键扭曲。光谱方法和 MM2 计算表明，溶液中 2 的扭曲明显大于 1（48° 对 MM2 的 25°）。X射线晶体学分析表明，1中两个苯基-嘧啶平面交叉点的扭转角为10°和19°。1的DNA结合常数与其他强嵌入剂的DNA结合常数相似，粘度测定、流动二色性和核磁共振实验（1 的不可交换质子、亚氨基质子和复合物中 DNA 的 31P 光谱）表明 1 通过嵌入与 DNA 结合。2 的结合常数小于 1，粘度、二色性和 NMR 实验表明 2 不嵌入。1、结构 具有扭曲的芳香系统和末端基本功能，类似于许多凹槽结合化合物，因此出乎意料的是 1 与 DNA 形成了强大的嵌入复合物。1 的扭曲可以补充或增强 DNA 碱基对的固有螺旋桨扭曲以允许嵌入。分子力学方法在六聚体 d(TACGTA) 的 CG 嵌入位点定位了两个潜在的低能嵌入构象 1。以动力学为由拒绝在每个
• Design, Synthesis, and Evaluation of Novel Biarylpyrimidines:  A New Class of Ligand for Unusual Nucleic Acid Structures
  作者：Richard T. Wheelhouse、Sharon A. Jennings、Victoria A. Phillips、Dimitrios Pletsas、Peter M. Murphy、Nichola C. Garbett、Jonathan B. Chaires、Terence C. Jenkins

  DOI：10.1021/jm060315a

  日期：2006.8.1

  Biarylpyrimidines are characterized as selective ligands for higher-order nucleic acid structures. A concise and efficient synthesis has been devised incorporating Suzuki biaryl cross-coupling of dihalopyrimidines. Two ligand series are described based on the parent thioether 4,6-bis[4-[[2-(dimethylamino)ethyl]mercapto]phenyl] pyrimidine (1a) and amide 4,6-bis(4[(2-(dimethylamino) ethyl) carboxamido] phenyl) pyrimidine (2a) compounds. In UV thermal denaturation studies with the poly(dA),[poly(dT)](2) triplex structure, thioethers showed stabilization of the triplex form (Delta T-m <= 20 degrees C). In contrast, amides showed duplex stabilization (Delta T-m <= 15 degrees C) and either negligible stabilization or specific destabilization (Delta T-m = 5 degrees C) of the triplex structure. Full spectra of nucleic acid binding preferences were determined by competition dialysis. The strongest interacting thioether bound preferentially to the poly(dA)(.)[poly(dT)](2) triplex, Kapp) 1.6 x 10(5) M-1 (40 x Kapp for CT DNA duplex). In contrast, the strongest binding amide selected the (T(2)G(20)T(2)) 4 quadruplex structure, Kapp) 0.31 x 10(5) M-1 (6.5 x K-app for CT DNA duplex).
• [EN] NUCLEIC ACID INTERACTING UNFUSED HETEROPOLYCYCLIC COMPOUNDS
  申请人：GEORGIA STATE UNIVERSITY FOUNDATION, INC.

  公开号：WO1989011279A1

  公开（公告）日：1989-11-30

  (EN) The compounds of the present invention are derivatized unfused heteropolycyclic compounds, primarily heterotricyclic compounds, formed by replacing the halogen atoms adjacent to diazine ring nitrogens or the benzylic halogenin 2,6-bis[4-(bromomethyl)phenyl]pyridine with one of a variety of common nucleophiles such as the hydroxide ion, alkoxides, mercaptides, and amines. These compounds interact with nucleic acids, thereby inhibiting translation and interfering with viral replication processes, such as the replication of HIV, the virus believed to cause AIDS. The preferred compounds at this time are 2,6-bis[4'-[(dimethylamino)methyl]phenyl]pyridine (DH-23); 4,6-bis[4'-[[2''-(dimethylamino)ethyl]thio]phenyl]-5-methylpyrimidine (LS-22); N-[2''-(dimethylamino)ethyl]-4-(benzo[b]thiophen-2'-yl)quinazolin-2-amine (M-116); N,N-bis(2''''-hydroxyethyl)-2-[[4'-(benzo[b]thiopen-2''-yl)-6'-(thien-2'''-yl)pyrimidin-2'-yl]oxy]ethylamine (DH-42); bis-4,6-[4'-[[2''-(dimethylamino)ethyl]thio]phenyl]pyrimidine (LS-20); 1-methyl-4-[2'-[[4''-(naphth-2'''-yl) quinazolin-2''-yl]thio]ethyl]piperazine (M-69); N,N-bis-(2'-hydroxyethyl)-4,6-bis(thien-2''-yl)pyrimidin-2-amine (M-103); N,N-bis(2'-hydroxyethyl)-2-[[4'',6''-bis(thien-2'''-yl)pyrimidine-2''yl]oxy]ethylamine (M-105); and 4-[3'-[[2''-(dimethylamino)ethyl]thio]phenyl]-2-[[2'''-(dimethylamino)ethyl]thio] pyrimidine (DH-19). Advantages of these compounds include low cost and ease of manufacture.(FR) Les composés de la présente invention sont des composés hétéropolycycliques non fusionnés dérivés, essentiellement des composés hétérotricycliques, formés en remplaçant les atomes d'halogène adjacents aux atomes d'azote de l'anneau diazine ou l'halogénine benzylique 2,6-bis[4-(bromométhyle)phényle]pyridine avec un nucléophile d'une variété de nucléophiles communs tels que l'ion hydroxyde, des alcoxydes, des mercaptides et des amines. Ces composés ont une interaction avec des acides nucléiques, inhibant ainsi la translation et interférant avec des procédés de réplication virale, tels que la réplication de HIV, le virus provoquant le SIDA. Les composés préférés sont 2,6-bis[4'-[diméthylamino]méthyle]phényle]pyridine (DH-23); 4,6-bis[4'-[[2''-(diméthylamino)éthyle]thio]phényle]-5-méthylpyrimidine (LS-22); N-[2''-(diméthylamino)éthyle]-4-(benzo[b]thiophène-2'-yle)quinazoline-2-amine (M-116); N,N-bis(2''''-hydroxyéthyle)-2-[[4'-(benzo[b]thiophène-2''-yle)-6'-(thiène-2'''-yl)pyrimidine-2'-yle]oxy]éthylamine (DH-42); bis-4,6-[4'-[[2''-(diméthylamino)éthyle]thio]phényle]pyrimidine (LS-20); 1-méthyle-4-[2'-[[4''-(naphth-2'''-yle) quinazoline-2''-yle]thio]éthyle]pipérazine (M-69); N,N-bis-(2'-hydroxyéthyle)-4,6-bis(thiène-2''-yle)pyrimidine-2-amine (M-103); N,N-bis(2'-hydroxyéthyle)-2-[[4'',6''-bis(thiène-2'''-yle)pyrimidine-2''yle]oxy]éthylamine (M-105); et 4-[3'-[[2''-(diméthylamino)éthyle]thio]phényle]-2-[[2'''-(diméthylamino)éthyle]thio] pyrimidine (DH-19). Ces composés sont avantageux car ils sont peu coûteux et faciles à produire.
• Biarylpyrimidines: a new class of ligand for high-order DNA recognitionElectronic supplementary information (ESI) available: experimental details of UV melting studies and example spectroscopic and analytical data. See http://www.rsc.org/suppdata/cc/b3/b301554h/
  作者：Peter M. Murphy、Victoria A. Phillips、Sharon A. Jennings、Nichola C. Garbett、Jonathan B. Chaires、Terence C. Jenkins、Richard T. Wheelhouse

  DOI：10.1039/b301554h

  日期：2003.4.30

  Biarylpyrimidines bearing ω-aminoalkyl substituents have been designed as ligands for high-order DNA structures: spectrophotometric, thermal and competition equilibrium dialysis assays showed that changing the functional group for substituent attachment from thioether to amide switches the structural binding preference from triplex to tetraplex DNA; the novel ligands are non-toxic and moderate inhibitors of human telomerase.

  具有ω-氨基烷基取代基的联苯嘧啶类化合物已被设计为高阶DNA结构的配体：分光光度法、热学法及竞争平衡透析法检测显示，将取代基连接的功能基团由硫醚改为酰胺，可使其结构结合偏好从三链DNA转变为四链DNA；新型的配体无毒且对人类端粒酶具有中等抑制作用。