3-morpholino-5-(3',4',5'-trimethoxybenzyl)acrylopyrimidine | 30077-81-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-morpholino-5-(3',4',5'-trimethoxybenzyl)acrylopyrimidine
• 英文别名: 3-morpholin-4-yl-2-(3,4,5-trimethoxy-benzyl)-acrylonitrile；α-(3,4,5-Trimethoxybenzyl)-ss-morpholino-acrylonitril；3-Morpholino-2-(3,4,5-trimethoxybenzyl)acrylonitrile；(Z)-3-morpholin-4-yl-2-[(3,4,5-trimethoxyphenyl)methyl]prop-2-enenitrile
• CAS: 30077-81-7
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: COJLXRBNOHYGDQ-OWBHPGMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-morpholino-5-(3',4',5'-trimethoxybenzyl)acrylopyrimidine 、 胍 在 二甲基亚砜 作用下， 以 乙醇 为溶剂， 生成 甲氧苄啶
  参考文献：
  名称：

  Immobilization of Malarial (Plasmodium falciparum) Dihydrofolate Reductase for the Selection of Tight-Binding Inhibitors from Combinatorial Library

  摘要：

  已经描述了一种基于优先结合固定在Sepharose柱上的酶的选择突变型恶性疟原虫二氢叶酸还原酶（PfDHFRs）的紧密结合抑制剂的简单程序。为了通过S-S键固定到硫丙基-Sepharose凝胶上，制备了在C末端具有半胱氨酸残基的PfDHFRs。估计固定化的DHFRs量为4-5毫克/克干燥凝胶，并且与自由酶的活性相当。制备的固定化酶已被用于从组合库中选择紧密结合抑制剂，基于每个配体与酶的亲和力。然后通过高效液相色谱-质谱法识别和定量分析自由配体，从而实现库中具有高结合亲和力的成分。结果可以通过定量分析通过盐酸胍处理从酶中释放的结合配体来确认。

  DOI：

  10.1021/ac070215s
• 作为产物：
  描述：

  3-(4-吗啉基)丙腈 、 3,4,5-三甲氧基苯甲醛 在 sodium methylate 作用下， 以 二甲基亚砜 为溶剂， 生成 3-morpholino-5-(3',4',5'-trimethoxybenzyl)acrylopyrimidine
  参考文献：
  名称：

  Immobilization of Malarial (Plasmodium falciparum) Dihydrofolate Reductase for the Selection of Tight-Binding Inhibitors from Combinatorial Library

  摘要：

  已经描述了一种基于优先结合固定在Sepharose柱上的酶的选择突变型恶性疟原虫二氢叶酸还原酶（PfDHFRs）的紧密结合抑制剂的简单程序。为了通过S-S键固定到硫丙基-Sepharose凝胶上，制备了在C末端具有半胱氨酸残基的PfDHFRs。估计固定化的DHFRs量为4-5毫克/克干燥凝胶，并且与自由酶的活性相当。制备的固定化酶已被用于从组合库中选择紧密结合抑制剂，基于每个配体与酶的亲和力。然后通过高效液相色谱-质谱法识别和定量分析自由配体，从而实现库中具有高结合亲和力的成分。结果可以通过定量分析通过盐酸胍处理从酶中释放的结合配体来确认。

  DOI：

  10.1021/ac070215s

文献信息

• Processes for preparing tri-heterocyclic substituted methanes and their conversion into further intermediates useful in the preparation of pharmacologically active compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0001633A1

  公开（公告）日：1979-05-02

  The present invention provides a process for preparing useful chemical intermediates, tri-heterocyclic substituted methanes, and their conversion into further intermediates useful in the preparation of pharmacologically active compounds, such as trimethoprim and allopurinol.

  本发明提供了一种制备有用的化学中间体，三杂环取代甲烷及其转化为进一步中间体的过程，这些中间体可用于制备药理活性化合物，如曲唑酮和痛风宁。
• Development of 2,4-Diaminopyrimidines as Antimalarials Based on Inhibition of the S108N and C59R+S108N Mutants of Dihydrofolate Reductase from Pyrimethamine-Resistant <i>Plasmodium </i><i>f</i><i>alciparum</i>
  作者：Bongkoch Tarnchompoo、Chawanee Sirichaiwat、Worrapong Phupong、Chakapong Intaraudom、Worachart Sirawaraporn、Sumalee Kamchonwongpaisan、Jarunee Vanichtanankul、Yodhathai Thebtaranonth、Yongyuth Yuthavong

  DOI：10.1021/jm010131q

  日期：2002.3.1

  The reduced binding of pyrimethamine to Ser 108Asn (S108N) mutants of parasite dihydrofolate reductase (DHFR), which forms the basis of resistance of Plasmodium falcipartum to pyrimethamine, is largely due to steric constraint imposed by the bulky side chain of N108 on Cl of the 5-p-Cl-phenyl group. This and other S108 mutants with bulky side chains all showed reduced binding to pyrimethamine and cycloguanil. Less effect on binding to some bulky mutants was observed for trimethoprim, with greater flexibility for the 5-substituent. S108N DHFR also binds poorly with other pyrimethamine derivatives with bulky groups in place of the p-Cl, and the binding was generally progressively poorer for the double (C59R+S108N) mutant. Removal of the p-Cl or replacement with m-Cl led to better binding with the mutant DHFRs. Pyrimethamine analogues with unbranched hydrophobic 6-substituents showed generally good binding with the mutant DHFRs. A number of compounds were identified with high affinities for both wild-type and mutant DHFRs, with very low to no affinity to human DHFR. Some of these compounds show good antimalarial activities against pyrimethamine-resistant P. falciparum containing the mutant DHFRs with low cytotoxicity to three mammalian cell lines.
• SWARINGEN R. A. JR.; EADDY J. F.; HENDERSON T. R., J. ORG. CHEM., 1980, 45, NO 20, 3986-3989
  作者：SWARINGEN R. A. JR.、 EADDY J. F.、 HENDERSON T. R.

  DOI：——

  日期：——
• US4052553A
  申请人：——

  公开号：US4052553A

  公开（公告）日：1977-10-04