(3,5-dibromophenoxy)triisopropylsilane | 915411-64-2

• 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: (3,5-dibromophenoxy)triisopropylsilane
• 英文别名: 3,5-dibromotriisopropylsiloxybenzene；(3,5-Dibromo-phenoxy)-triisopropyl-silane；(3,5-dibromophenoxy)-tri(propan-2-yl)silane
• CAS: 915411-64-2
• 化学式: C₁₅H₂₄Br₂OSi
• 分子量: 408.248
• InChiKey: RRJPQTBZKCCDSP-UHFFFAOYSA-N

物化性质

• 沸点：
  350.9±32.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.77
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (3,5-dibromophenoxy)triisopropylsilane 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 potassium phosphate 、 2’-(dimethylamino)-2-biphenylylpalladium(II) chloride dinorbornylphosphine complex 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

  摘要：

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model

  DOI：

  10.1021/jm100659v
• 作为产物：
  描述：

  2,6-二溴-4-硝基苯胺 在 氢氧化钾 、 硫酸 、 四丁基溴化铵 、 氢溴酸 、 sodium hydride 、 1,1,3,3-四甲基脲 、 sodium nitrite 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 (3,5-dibromophenoxy)triisopropylsilane
  参考文献：
  名称：

  Anti-cancer agents and uses thereof

  摘要：

  本发明涉及新化合物及其盐，它们的合成以及它们作为抗癌剂的用途。这些化合物包括式I的化合物： 和其溶剂化物、水合物和药用可接受盐，其中A 1 为N或CR 1 ；A 3 为N或CR 3 ；A 5 为N或CR 5 ；R 1 ，R 3 -R 6 和L在规范中定义；n为0或1；X为在环部分具有6-10个碳的可选择取代芳基，在环部分具有1-3个氮原子的可选择取代的6元杂芳基，在环部分具有0-4个氮原子且可选择在环部分有1个硫原子或1个氧原子的可选择取代的5元杂芳基，或者在其中6元环与5元环或6元环融合的可选择取代的杂芳基，其中在每种情况下1、2、3或4个环原子是从氮、氧和硫中独立选择的杂原子。它们对广泛范围的癌症，特别是白血病、前列腺癌、非小细胞肺癌和结肠癌有效。它们还可用于治疗增殖性视网膜病变，如糖尿病神经病变和黄斑变性。

  公开号：

  US20080280891A1

文献信息

• ANTI-CANCER AGENTS AND USES THEREOF
  申请人：KELLY Martha

  公开号：US20090093479A1

  公开（公告）日：2009-04-09

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 -R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成方法以及它们作为抗癌剂的用途。这些化合物包括式I的化合物及其溶剂化物、水化物和药学上可接受的盐，其中A1为N或CR1；A3为N或CR3；A5为N或CR5；R1、R3-R6和L在规范中有定义；n为0或1；X是一个具有6-10个碳原子的环部分可选取代的芳基基团，一个具有1-3个氮原子的环部分可选取代的6元杂芳基基团，一个具有0-4个氮原子并可选地在环部分含有1个硫原子或1个氧原子的5元杂芳基基团，或者一个6元环与一个5元环或6元环融合的可选取代的杂芳基基团，在每种情况下，1、2、3或4个环原子是独立选择的氮、氧和硫杂原子。它们对广泛的癌症，尤其是白血病、非小细胞肺癌和结肠癌都有良好的治疗效果。
• WO2008/8059
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Pharmacological Evaluation of <i>N</i>-(3-(1<i>H</i>-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent
  作者：Rupa S. Shetty、Younghee Lee、Bin Liu、Arifa Husain、Rhoda W. Joseph、Yixin Lu、David Nelson、John Mihelcic、Wenchun Chao、Kristofer K. Moffett、Andreas Schumacher、Dietmar Flubacher、Aleksandar Stojanovic、Marina Bukhtiyarova、Ken Williams、Kyoung-Jin Lee、Alexander R. Ochman、Michael S. Saporito、William R. Moore、Gary A. Flynn、Bruce D. Dorsey、Eric B. Springman、Ted Fujimoto、Martha J. Kelly

  DOI：10.1021/jm100659v

  日期：2011.1.13

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model
• Anti-cancer agents and uses thereof
  申请人：Kelly Martha

  公开号：US20060270686A1

  公开（公告）日：2006-11-30

  The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A 1 is N or CR 1 ; A 3 is N or CR 3 ; A 5 is N or CR 5 ; R 1 , R 3 —R 6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.

  本发明涉及新化合物及其盐，它们的合成以及它们作为抗癌剂的用途。这些化合物包括式I的化合物： 和其溶剂化物、水合物和药用可接受盐，其中A 1 为N或CR 1 ；A 3 为N或CR 3 ；A 5 为N或CR 5 ；R 1 ，R 3 —R 6 和L在说明书中有定义；n为0或1；X为在环部分具有6-10个碳的可选择取代芳基，在环部分具有1-3个氮原子的可选择取代的6元杂芳基，在环部分具有0-4个氮原子且可选择具有1个硫原子或1个氧原子的可选择取代的5元杂芳基，或者在其中6元环与5元环或6元环融合的可选择取代的杂芳基，其中在每种情况下1、2、3或4个环原子是从氮、氧和硫中独立选择的杂原子。它们对广泛范围的癌症，特别是白血病、非小细胞肺癌和结肠癌有效。