3-oxo-2-phenyl-nonanenitrile | 859987-91-0

• 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-oxo-2-phenyl-nonanenitrile
• 英文别名: 3-Oxo-2-phenyl-nonannitril；3-Oxo-2-phenylnonanenitrile
• CAS: 859987-91-0
• 化学式: C₁₅H₁₉NO
• 分子量: 229.322
• InChiKey: JKJXNOOWSVJEIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-oxo-2-phenyl-nonanenitrile 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 0.08h， 生成 6-己基-5-苯基嘧啶-2,4-二胺
  参考文献：
  名称：

  Development of 2,4-Diaminopyrimidines as Antimalarials Based on Inhibition of the S108N and C59R+S108N Mutants of Dihydrofolate Reductase from Pyrimethamine-Resistant Plasmodium falciparum

  摘要：

  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.

  DOI：

  10.1021/jm010131q
• 作为产物：
  描述：

  苯乙腈 、 庚酰氯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 3-oxo-2-phenyl-nonanenitrile
  参考文献：
  名称：

  Antimalarial pyrimidine derivatives and methods of making and using them

  摘要：

  公式（I）中，R1代表氢原子或3-卤原子，R2代表直链烷基，含有多达6个碳原子的直链烷基，含有未取代或取代芳香环的多达3个碳原子的直链烷基，或在末端位置具有烷氧羰基取代基，或芳氧基烷氧基烷基取代基已被发现对疟原虫富马酸盐株具有抗疟活性，包括对嘧啶嘧啶和其他抗叶酸类药物产生抗药性的株。本文揭示了这些化合物本身、制备这些化合物的方法以及使用这些化合物的方法。

  公开号：

  US20040180913A1

文献信息

• Bobranski, Acta Poloniae Pharmaceutica, 1953, vol. 10, p. 1,5
  作者：Bobranski

  DOI：——

  日期：——
• 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.
• Antimalarial pyrimidine derivatives and methods of making and using them
  申请人：National Science and Technology Development Agency

  公开号：US20040180913A1

  公开（公告）日：2004-09-16

  Compounds of the formula (I) wherein R 1 represents a hydrogen atom or a 3-halogen atom, and R 2 represents a straight-chain alkyl group containing up to 6 carbon atoms, a straight-chain alkyl group containing up to 3 carbon atoms with unsubstituted or substituted aromatic ring, or alkoxycarbonyl substituent at the end position, or aryloxyalkoxyalkyl group have been found to possess antimalarial activity against Plasmodium falciparum lines, including those resistant against pyrimethamine and other antifolates. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed.

  公式（I）中，R1代表氢原子或3-卤原子，R2代表直链烷基，含有多达6个碳原子的直链烷基，含有未取代或取代芳香环的多达3个碳原子的直链烷基，或在末端位置具有烷氧羰基取代基，或芳氧基烷氧基烷基取代基已被发现对疟原虫富马酸盐株具有抗疟活性，包括对嘧啶嘧啶和其他抗叶酸类药物产生抗药性的株。本文揭示了这些化合物本身、制备这些化合物的方法以及使用这些化合物的方法。