二甲基[(2,5-二苄氧基)苯基甲基]膦酸酯 | 135203-64-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 二甲基[(2,5-二苄氧基)苯基甲基]膦酸酯
• 英文名称: dimethyl <<2,5-bis(benzyloxy)phenyl>methyl>phosphonate
• 英文别名: dimethyl <(2,5-bis(dibenzyloxy)phenyl)methyl>phosphate；Dimethyl [(2,5-Dibenzyloxy)phenylmethyl]phosphonate；2-(dimethoxyphosphorylmethyl)-1,4-bis(phenylmethoxy)benzene
• CAS: 135203-64-4
• 化学式: C₂₃H₂₅O₅P
• 分子量: 412.422
• InChiKey: ZJAZZTJXQSSAMZ-UHFFFAOYSA-N

物化性质

• 熔点：
  62-64°C
• 沸点：
  560.3±50.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷、DMSO、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二甲基[(2,5-二苄氧基)苯基甲基]膦酸酯 在 sodium hydroxide 、 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (E)-5-[2-(Bezn基氧基)2-[2,5-二(苄氧基)苯基]乙烯基]-苯甲酸
  参考文献：
  名称：

  Non-amine based analogs of lavendustin A as protein-tyrosine kinase inhibitors

  摘要：

  The fermentation product lavendustin A (1) is a protein-tyrosine kinase (PTK) inhibitor whose active pharmacophore has previously been shown to reside in the more simplified salicyl-containing benzylamine 2. Amine 2 bears some structural resemblance to two other natural product PTK inhibitors, erbstatin (3) and piceatannol (4). Non-amine containing analogues of 2 were therefore synthesized which incorporated additional aspects of either erbstatin or piceatannol. Examination of these inhibitors in immunoprecipitated p56lck, epidermal growth factor receptor (EGFR), and c-erb B-2/HER 2/neu PTK preparations showed that compound 12 (IC50 = 60 nM) was one of the most potent p56lck inhibitors reported to date. These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and -ethenes bearing a salicyl moiety appear to be valuable structural motifs for the construction of extremely potent PTK inhibitors.

  DOI：

  10.1021/jm00072a022
• 作为产物：
  描述：

  2,5-bisbenzyloxybenzyl chloride 、 三甲氧基磷 以89%的产率得到二甲基[(2,5-二苄氧基)苯基甲基]膦酸酯
  参考文献：
  名称：

  Non-amine based analogs of lavendustin A as protein-tyrosine kinase inhibitors

  摘要：

  The fermentation product lavendustin A (1) is a protein-tyrosine kinase (PTK) inhibitor whose active pharmacophore has previously been shown to reside in the more simplified salicyl-containing benzylamine 2. Amine 2 bears some structural resemblance to two other natural product PTK inhibitors, erbstatin (3) and piceatannol (4). Non-amine containing analogues of 2 were therefore synthesized which incorporated additional aspects of either erbstatin or piceatannol. Examination of these inhibitors in immunoprecipitated p56lck, epidermal growth factor receptor (EGFR), and c-erb B-2/HER 2/neu PTK preparations showed that compound 12 (IC50 = 60 nM) was one of the most potent p56lck inhibitors reported to date. These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and -ethenes bearing a salicyl moiety appear to be valuable structural motifs for the construction of extremely potent PTK inhibitors.

  DOI：

  10.1021/jm00072a022

文献信息

• Disubstituted lavendustin A analogs and pharmaceutical compositions comprising the analogs
  申请人：THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP1367046A9

  公开（公告）日：2004-05-12

  Disubstituted lavendustin A analogs that are PTK inhibitors having antiproliferative activity are described. Preferred compounds of the present invention, without limitation, satisfy either Formula 1 or Formula 2. Currently preferred compounds ,based on in vivo biological activity, are 4'-adamantylbenzoate-1'-N-1,4-dihydroxybenzylamine and 4'-adamantylmethylbenzoate-1'-N-1,4-dihydroxybenzylamine. The present invention also provides pharmaceutical compositions comprising effective amounts of disubstituted lavendustin A analogs. Such compositions also may comprise other active ingredients, other materials conventionally used in the formulation of pharmaceutical composition, and mixtures thereof. The compounds and compositions of the present invention can be used for treating subjects to, for example, inhibit the proliferation of living cells in the treatment of proliferative diseases.

  描述了具有抗增殖活性的PTK抑制剂的二取代拉文杜斯汀A类似物。本发明的优选化合物，不受限于，满足Formula 1或Formula 2中的任一种。根据体内生物活性，目前优选的化合物是4'-金刚烷基苯甲酸酯-1'-N-1,4-二羟基苯乙胺和4'-金刚烷基甲基苯甲酸酯-1'-N-1,4-二羟基苯乙胺。本发明还提供了含有二取代拉文杜斯汀A类似物有效量的药物组合物。这种组合物还可以包括其他活性成分、传统用于制备药物组合物的其他材料以及它们的混合物。本发明的化合物和组合物可用于治疗受试者，例如，在治疗增殖性疾病中抑制活细胞的增殖。
• Bis(bibenzyl) ethers from Pellia endiviifolia
  作者：Toshihiro Hashimoto、Hazimu Suzuki、Motoo Tori、Yoshinori Asakawa

  DOI：10.1016/0031-9422(91)84201-3

  日期：1991.1

  Abstract Two new bis(bibenzyl) ethers, perrottetin E-11′-methyl ether and 14-hydroxyperrottetin E-11′-methyl ether were isolated from an ethyl acetate extract of the liverwort Pellia endiviifolia together with the previously known bis(bibenzyl) ether, perrottetin E and their structures characterized by spectroscopic methods, chemical evidence and total synthesis. The present results strongly support

  摘要 两种新的双（联苄基）醚，perrottetin E-11'-甲基醚和 14-羟基 perrottetin E-11'-甲基醚与先前已知的双（联苄基）醚一起从苔藓 Pellia endiviifolia 的乙酸乙酯提取物中分离出来。 ，perrottetin E 及其结构特征的光谱方法，化学证据和全合成。目前的结果强烈支持舒斯特对 Metzgeriales 和 Jungermanniales 的系统发育分类。
• HASHIMOTO, TOSHIHIRO;SUZUKI, HAZIMU;TORI, MOTOO;ASAKAWA, YOSHINORI, PHYTOCHEMISTRY, 30,(1991) N, C. 1523-1530
  作者：HASHIMOTO, TOSHIHIRO、SUZUKI, HAZIMU、TORI, MOTOO、ASAKAWA, YOSHINORI

  DOI：——

  日期：——