2-(benzo[d][1,3]dioxol-5-yl)-3-oxopentanenitrile | 182425-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 2-(benzo[d][1,3]dioxol-5-yl)-3-oxopentanenitrile
• 英文别名: 2-(1,3-Benzodioxol-5-yl)-3-oxopentanenitrile
• CAS: 182425-74-7
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: SRUZKVZBWNFCMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(benzo[d][1,3]dioxol-5-yl)-3-oxopentanenitrile 在 甲烷磺酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以72%的产率得到4-(benzo[d][1,3]dioxol-5-yl)-3-ethyl-1H-pyrazol-5-amine
  参考文献：
  名称：

  3,4-取代的5-氨基吡唑和4-取代的-2-氨基噻唑的制备

  摘要：

  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）。

  DOI：

  10.1021/acs.joc.8b02655
• 作为产物：
  描述：

  丙酸乙酯 、 1,3-苯并二氧杂环戊烯-5-乙腈 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 2-(benzo[d][1,3]dioxol-5-yl)-3-oxopentanenitrile
  参考文献：
  名称：

  Potential Antimalarials. XXII. Some 2,4-Diamino-5-(3- and 4-trifluoromethylphenyl and 3,4-methylenedioxyphenyl)pyrimidines

  摘要：

  一系列含有3'-和4'-三氟甲基和3',4'-亚甲二氧基基团的10个嘧啶胺类似物已经制备并针对Plasmodium falciparum的FC-27和K-1菌株进行了体外抗疟活性测试。其中几种化合物对于对药物敏感的FC-27菌株的活性几乎与嘧啶胺相当，而像嘧啶胺一样，它们对于对药物耐药的K-1菌株的活性要低得多。然而，4'-三氟甲基化合物显示出较小的差异。

  DOI：

  10.1071/ch9960647

文献信息

• 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.
• 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）。
• Potential Antimalarials. XXII. Some 2,4-Diamino-5-(3- and 4-trifluoromethylphenyl and 3,4-methylenedioxyphenyl)pyrimidines
  作者：GB Barlin、B Kotecka、KH Rieckmann

  DOI：10.1071/ch9960647

  日期：——

  A series of 10 pyrimethamine analogues containing 3'- and 4'-trifluoromethyl and 3',4'-methylenedioxy groups has been prepared and tested for in vitro antimalarial activity against the FC-27 and K-1isolates of Plasmodium falciparum. Several of these compounds were almost as active as pyrimethamine against the drug-sensitive FC-27 isolate, and like pyrimethamine , they were much less active against the drug-resistant K-1 isolate. The 4'-trifluoromethyl compunds, however, showed much smaller differences.

  一系列含有3'-和4'-三氟甲基和3',4'-亚甲二氧基基团的10个嘧啶胺类似物已经制备并针对Plasmodium falciparum的FC-27和K-1菌株进行了体外抗疟活性测试。其中几种化合物对于对药物敏感的FC-27菌株的活性几乎与嘧啶胺相当，而像嘧啶胺一样，它们对于对药物耐药的K-1菌株的活性要低得多。然而，4'-三氟甲基化合物显示出较小的差异。