3-[3-(tert-butyldimethylsilanyloxy)-4-methoxyphenyl]-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazole | 701954-65-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[3-(tert-butyldimethylsilanyloxy)-4-methoxyphenyl]-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazole
• 英文别名: Tert-butyl-[2-methoxy-5-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]phenoxy]-dimethylsilane；tert-butyl-[2-methoxy-5-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]phenoxy]-dimethylsilane
• CAS: 701954-65-6
• 化学式: C₂₅H₃₅NO₆Si
• 分子量: 473.642
• InChiKey: YMOPECJMPLLNJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.97
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[3-(tert-butyldimethylsilanyloxy)-4-methoxyphenyl]-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazole 在 manganese(IV) oxide 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 0.33h， 生成 2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenol
  参考文献：
  名称：

  Heterocyclic and Phenyl Double-Bond-Locked Combretastatin Analogues Possessing Potent Apoptosis-Inducing Activity in HL60 and in MDR Cell Lines

  摘要：

  Two new series of combretastatin (CA-4) analogues have been prepared. The alkenyl motif of CA-4 was replaced either by a five-membered heterocyclic (isoxazoline or isoxazole) or by a six-membered ring (pyridine or benzene). The new compounds have been evaluated for their effects on tubulin assembly and for cytotoxic and apoptotic activities. Five compounds (18b, 20a, 21a, 34b, and 35b) demonstrated an attractive profile of cytotoxicity (IC50 < 1 muM) and apoptosis-inducing activity but poor antitubulin activity. The isoxazoline derivatives 18b, 20a, and 21a, demonstrated potent apoptotic activity different from that of natural CA-4. Their ability to block most cells in the G2 phase suggests that these compounds could act on targets different from the mitotic spindle. This would indicate activation of both the intrinsic and the extrinsic apoptotic pathways. The data suggest unambiguously that structural alteration of the stilbene motif of CA-4 can be extremely effective in producing potent apoptosis-inducing agents.

  DOI：

  10.1021/jm049622b
• 作为产物：
  描述：

  3-叔-丁基二甲基硅氧基-4-甲氧基苯甲醛 在 吡啶 、 sodium hypochlorite 、 盐酸羟胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 3-[3-(tert-butyldimethylsilanyloxy)-4-methoxyphenyl]-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazole
  参考文献：
  名称：

  Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation

  摘要：

  Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 mu M), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.001

文献信息

• [EN] COMBRETASTATIN DERIVATIVES WITH CYTOTOXIC ACTION<br/>[FR] DERIVES DE LA COMBRETASTATINE A ACTION CYTOTOXIQUE
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2005007635A3

  公开（公告）日：2005-08-11
• 1,3-Dipolar cycloaddition route to novel isoxazole-type derivatives related to combretastatin A-4
  作者：Julia Kaffy、Claude Monneret、Patrick Mailliet、Alain Commerçon、Renée Pontikis

  DOI：10.1016/j.tetlet.2004.03.020

  日期：2004.4

  A series of compounds related to combretastatin A-4, containing a five-membered heterocyclic ring interposed between the two phenyl groups have been Prepared. Synthetic approach involves 1,3-dipolar cycloaddition of various 3,4,5-trimethoxyphenyl units with an in situ generated nitrile oxide from a suitable aldoxime using sodium hypochlorite. Depending oil the nature of the dipolarophile, 3,5-diarylisoxazole derivatives obtained along with the 3,4-regioisomeric isomers. (C) 2004 Elsevier Ltd. All rights reserved.