3,6-bis(4-cyanophenyl)pyridazine | 73550-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3,6-bis(4-cyanophenyl)pyridazine
• 英文别名: 2,5-bis-(4'-cyanophenyl)-pyridazine；3,6-Bis[p-cyanophenyl]pyridazine；4-[6-(4-cyanophenyl)pyridazin-3-yl]benzonitrile
• CAS: 73550-85-3
• 化学式: C₁₈H₁₀N₄
• 分子量: 282.304
• InChiKey: UZRMBLASDBLYJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,6-bis(4-cyanophenyl)pyridazine 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 84.0h， 生成 3,6-Bis-[4-(1,4,5,6-tetrahydro-pyrimidin-2-yl)-phenyl]-pyridazine
  参考文献：
  名称：

  一些双（4-胍基苯基）五元和六元环杂环的合成及抗胰蛋白酶活性。

  摘要：

  2,5-双（4-胍基苯基）-1,3-恶唑，2,5-双（4-胍基苯基）-1,3,4-恶二唑和-1,3,4-噻二唑和3,6-已经合成了双（4-胍基苯基）哒嗪及其一些“环状胍基”类似物。2,5-双（4-胍基苯基）-1,3-恶唑和-1,3,4-噻二唑对小鼠的罗氏锥虫表现出良好的活性，没有急性毒性，以3 mg / kg的剂量水平可以治愈。在该测试中，该活性与stilbamidine，hydroxystilbamidine和pentamidine相当。相反，在我们的测试系统中，2,5-双（4-胍基苯基）-1,3,4-恶二唑的活性急剧下降。通常，环状鸟苷类似物表现出低级活性，并且在中等剂量水平下开始出现毒性。

  DOI：

  10.1021/jm00179a022
• 作为产物：
  描述：

  3,6-二氯哒嗪 、 4-氰基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 以80%的产率得到3,6-bis(4-cyanophenyl)pyridazine
  参考文献：
  名称：

  Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum

  摘要：

  A series of azaterphenyl diamidines has been synthesized and evaluated for in vitro antiprotozoal activity against both Trypanosoma brucei rhodesiense (T. b .r.) and Plasmodium falciparum (P. f.) and in vivo efficacy in the STIB900 acute mouse model for T. b. r. Six of the 13 compounds showed IC50 values less than 7 nM against T. b. r. Twelve of those exhibited IC50 values less than 6 nM against P. f. and six of those showed IC50 values <= 60.6 nM, which are more than 25-fold as potent as furamidine. Moreover, two of them showed more than 40-fold selectivity for P. f. versus T. b. r. Three compounds 15b, 19d and 19e exhibited in vivo efficacy against T. b. r. much superior to furamidine, and equivalent to or better than azafuramidine. The antiparasitic activity of these diamidines depends on the ring nitrogen atom(s) location relative to the amidine groups and generally correlates with DNA binding affinity. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.07.080

文献信息

• Azaterphenyl diamidines as antileishmanial agents
  作者：Laixing Hu、Reem K. Arafa、Mohamed A. Ismail、Tanja Wenzler、Reto Brun、Manoj Munde、W. David Wilson、Sandra Nzimiro、Serene Samyesudhas、Karl A. Werbovetz、David W. Boykin

  DOI：10.1016/j.bmcl.2007.10.091

  日期：2008.1

  Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 mu M, five exhibited values less than 0.40 mu M, and two gave values less than 0.10 mu M in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes. (C) 2007 Elsevier Ltd. All rights reserved.
• DAS B. P.; WALLACE R. A.; BOYKIN D. W. JR., J. MED. CHEM., 1980, 23, NO 5, 578-581
  作者：DAS B. P.、 WALLACE R. A.、 BOYKIN D. W. JR.

  DOI：——

  日期：——
• Synthesis and antitrypanosomal activity of some bis(4-guanylphenyl) five- and six-membered ring heterocycles
  作者：Bijan P. Das、Rebecca A. Wallace、David Withers Boykin

  DOI：10.1021/jm00179a022

  日期：1980.5

  This activity is comparable to stilbamidine, hydroxystilbamidine, and pentamidine in this test. In contrast, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole shows a sharp reduction in activity in our test system. Generally, the cyclic guanyl analogues exhibit low orders of activity, and toxicity begins to appear at moderate dosage levels. All guanyl and cyclic guanyl compounds were synthesized from bisnitrile

  2,5-双（4-胍基苯基）-1,3-恶唑，2,5-双（4-胍基苯基）-1,3,4-恶二唑和-1,3,4-噻二唑和3,6-已经合成了双（4-胍基苯基）哒嗪及其一些“环状胍基”类似物。2,5-双（4-胍基苯基）-1,3-恶唑和-1,3,4-噻二唑对小鼠的罗氏锥虫表现出良好的活性，没有急性毒性，以3 mg / kg的剂量水平可以治愈。在该测试中，该活性与stilbamidine，hydroxystilbamidine和pentamidine相当。相反，在我们的测试系统中，2,5-双（4-胍基苯基）-1,3,4-恶二唑的活性急剧下降。通常，环状鸟苷类似物表现出低级活性，并且在中等剂量水平下开始出现毒性。
• Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum
  作者：Laixing Hu、Reem K. Arafa、Mohamed A. Ismail、Alpa Patel、Manoj Munde、W. David Wilson、Tanja Wenzler、Reto Brun、David W. Boykin

  DOI：10.1016/j.bmc.2009.07.080

  日期：2009.9

  A series of azaterphenyl diamidines has been synthesized and evaluated for in vitro antiprotozoal activity against both Trypanosoma brucei rhodesiense (T. b .r.) and Plasmodium falciparum (P. f.) and in vivo efficacy in the STIB900 acute mouse model for T. b. r. Six of the 13 compounds showed IC50 values less than 7 nM against T. b. r. Twelve of those exhibited IC50 values less than 6 nM against P. f. and six of those showed IC50 values <= 60.6 nM, which are more than 25-fold as potent as furamidine. Moreover, two of them showed more than 40-fold selectivity for P. f. versus T. b. r. Three compounds 15b, 19d and 19e exhibited in vivo efficacy against T. b. r. much superior to furamidine, and equivalent to or better than azafuramidine. The antiparasitic activity of these diamidines depends on the ring nitrogen atom(s) location relative to the amidine groups and generally correlates with DNA binding affinity. (C) 2009 Published by Elsevier Ltd.