2-(4-methoxyphenyl)-3-oxopentanenitrile | 5219-01-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-methoxyphenyl)-3-oxopentanenitrile
• 英文别名: 2-(4-methoxy-phenyl)-3-oxo-valeronitrile；(+/-)-3-Oxo-2-(4-methoxy-phenyl)-valeriansaeure-nitril；2-(4-Methoxy-phenyl)-3-oxo-valeronitril；2-<4-Methoxy-phenyl>-3-oxo-valeronitril；2-(4-Methoxy-phenyl)-3-oxo-pentanenitrile
• CAS: 5219-01-2
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: GPLHEHVQEKNGBG-UHFFFAOYSA-N

物化性质

• 熔点：
  87-88 °C
• 沸点：
  303.8±32.0 °C(Predicted)
• 密度：
  1.086±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-3-oxopentanenitrile 在 盐酸 、 碘乙烷 作用下， 生成 4-(4-methoxyphenyl)hexan-3-one
  参考文献：
  名称：

  v. Wessely et al., Monatshefte fur Chemie, 1941, vol. 73, p. 127,158

  摘要：

  DOI：
• 作为产物：
  描述：

  丙酸乙酯 、 对甲氧基苯乙腈 在 sodium ethanolate 作用下， 生成 2-(4-methoxyphenyl)-3-oxopentanenitrile
  参考文献：
  名称：

  v. Wessely et al., Monatshefte fur Chemie, 1941, vol. 73, p. 127,158

  摘要：

  DOI：

文献信息

• Preparation of 3,4-Substituted-5-Aminopyrazoles and 4-Substituted-2-Aminothiazoles
  作者：Stepan Havel、Prashant Khirsariya、Naresh Akavaram、Kamil Paruch、Benoit Carbain

  DOI：10.1021/acs.joc.8b02655

  日期：2018.12.21

  3,4-Substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles are frequently used intermediates in medicinal chemistry and drug discovery projects. We report an expedient flexible synthesis of 3,4-substituted-5-aminopyrazoles (35 examples), based on palladium-mediated α-arylation of β-ketonitriles with aryl bromides. A library of 4-substituted-2-aminothiazoles (21 examples) was assembled by a

  3,4-取代的5-氨基吡唑和4-取代的2-氨基噻唑是药物化学和药物开发项目中经常使用的中间体。我们报道了基于钯介导的β-酮腈与芳基溴化物的α-芳基化反应的3,4-取代的5-氨基吡唑类化合物的便捷合成（35个例子）。通过使用新制备的，适当保护的4-硼酸-2-氨基噻唑的频哪醇酯和MIDA酯与（杂）芳基卤化物的Suzuki偶联的序列，组装4-取代的2-氨基噻唑的文库（21个实例）。
• Mentzer et al., Bulletin de la Societe Chimique de France, 1946, p. 271,274
  作者：Mentzer et al.

  DOI：——

  日期：——
• Flavonoids. I. Synthesis of 2,2-Dialkyl-Δ³-isoflavenes from Coumarins¹
  作者：C. E. Cook、Robert C. Corley、Monroe E. Wall

  DOI：10.1021/jo01023a032

  日期：1965.12
• 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.
• Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-<i>N</i>-acetylhexosaminidase Activity
  作者：Michael B. Tropak、Jianmin Zhang、Sayuri Yonekawa、Brigitte A. Rigat、Virender S. Aulakh、Matthew R. Smith、Hee-Jong Hwang、Marco A. Ciufolini、Don J. Mahuran

  DOI：10.1021/jm5017895

  日期：2015.6.11

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.