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·338· 精细化工 FINE CHEMICALS 第 37 卷

反。此外，文献[32]报道了 7 个羟基咪唑并[1,2-a] idazole conjugates as potential anticancer agents[J]. Medicinal
吡啶化合物捕获 DPPH•百分数分别为 85%、57%、 Chemistry Communication, 2015, 6(4): 606-612.
[5] Saxena A, Schaper K J. QSAR analysis of the time- and dose-depen-
38%、89%、86%、90%和 78%，采用相同方法求得 dent anti-inflammatory in vivo activity of substituted imidazo[1,2-a]
的二茂铁基咪唑并[1,2-a]吡啶化合物Ⅱ~Ⅵ捕获 pyridines using artificial neural networks[J]. Qsar & Combinatorial
Science, 2010, 25(7): 590-597.
DPPH•百分数分别为 84.2%、77.7%、89.2%、86.7% [6] Márquez-Flores Y K, Campos-Aldrete M E, Salgado-Zamora H, et al.
和 94.5%，与文献中性能较好的 5 个羟基咪唑并 Docking simulations, synthesis, and anti-inflammatory activity eval-
[1,2-a]吡啶化合物相当。其中，化合物Ⅵ的抗氧化 uation of 2-(N-alkyl)amino-3-nitroimidazo[1,2-a]pyridines[J]. Medic-
inal Chemistry Research, 2011, 21(6): 775-782.
性能优于文献中活性最高的化合物，说明本文合成 [7] Kothavale S, Lee K H, Lee J Y. Novel 3-cyano imidazopyridine
的二茂铁基咪唑并[1,2-a]吡啶化合物具有较好的抗 acceptor-based bipolar and n-type host materials for phosphorescent
organic light-emitting diodes[J]. Asian Journal of Organic Chemistry,
氧化活性。
2018, 7(11): 2218-2222.
[8] Lee H, Li G Y, Jeong Y, et al. A novel imidazopyridine analogue as a
3 结论 phosphatidylinositol 3-kinase inhibitor against human breast cancer
[J]. Cancer Letters, 2012, 318(1): 68-75.
（1）采用 LaCl 3 催化 GBB-3CR，合成了 5 个二 [9] Xi G L, Liu Z Q. Introducing ferrocene into imidazo[1,2-a]pyridine
by Groebke three-component-reaction for scavenging radicals and
茂铁基咪唑并[1,2-a]吡啶化合物和 1 个咪唑并[1,2-a] inhibiting DNA oxidation[J]. Tetrahedron, 2015, 71(52): 9602-9610.
吡啶参比化合物，该方法具有反应时间短、产率高、 [10] Li P Z, Liu Z Q. Ferrocenyl-substituted curcumin: Can it influence
antioxidant ability to protect DNA?[J]. European Journal of Medici-
纯化方法简单等优点，并对目标化合物的结构进行
nal Chemistry, 2011, 46(5): 1821-1826.
了表征。 [11] Ralambomanana D A, Razafimahefa-Ramilison D, Rakotohova A C,
（2）在抑制 HO•引发的 DNA 氧化反应体系中， et al. Synthesis and antitubercular activity of ferrocenyl diaminoal-
cohols and diamines[J]. Bioorganic & Medicinal Chemistry, 2008,
二茂铁基团起到了促氧化的作用，而在抑制 GS•引 16(21): 9546-9553.
+
发的 DNA 氧化反应及捕获 ABTS •和 DPPH•体系 [12] Frett B, Mcconnell N, Smith C C, et al. Computer aided drug disco-
very of highly ligand efficient, low molecular weight imidazop-
中，二茂铁基团是有效的抗氧化官能团，能够极大
yridine analogs as FLT3 inhibitors[J]. European Journal of Medicinal
地提高咪唑并[1,2-a]吡啶化合物的抗氧化能力，且 Chemistry, 2015, 94: 123-131.
随数目的增加抗氧化性能不断增强，TBARS 百分数 [13] Kotla S K R, Choudhary D, Tiwari R K, et al. Cheminform abstract:
Rhodium(III)-catalyzed double C-H activation: A straightforward
最低可达 26.5%；在抑制自由基引发的 DNA 氧化反 approach to fused imidazo[1,2-a]pyridines from internal alkynes[J].
应及捕获自由基体系中，化合物Ⅱ、Ⅲ和Ⅴ的抗氧 Tetrahedron Letters, 2015, 56(32): 4706-4710.
[14] Yadav M, Dara S, Saikam V, et al. Regioselective oxidative C–H
化性能均遵循化合物Ⅴ>化合物Ⅱ>化合物Ⅲ的顺 phosphonation of imidazo[1,2-a]pyridines and related heteroarenes
序；在抑制自由基引发的 DNA 氧化反应及捕获 mediated by manganese(Ⅲ) acetate[J]. European Journal of Organic
+
ABTS •体系中，化合物Ⅱ的抗氧化性能优于化合物 Chemistry, 2015, 29: 6526-6533.
[15] Groebke K, Weber L, Mehlin F. Synthesis of imidazo[1,2-a] annu-
Ⅳ的性能，而在捕获 DPPH•体系中，化合物Ⅳ的性 lated pyridines, pyrazines and pyrimidines by a novel three-comp-
能优于化合物Ⅱ的性能。 onent condensation[J]. Synlett, 1998, 1998(6): 661-663.
[16] Blackburn C, Guan B, Fleming P, et al. Parallel synthesis of 3-amin-
（3）二茂铁基咪唑并[1,2-a]吡啶化合物不仅具 oimidazo[1,2-a]pyridines and pyrazines by a new three-component
有很好的自由基清除能力，还展现了一定的还原自 condensation[J]. Tetrahedron Letters, 1998, 39(22): 3635-3638.
[17] Bienaymé H, Bouzid K. A new heterocyclic multicomponent reaction
由基能力，具有一定的研究前景，也为今后继续从
for the combinatorial synthesis of fused 3-aminoimidazoles[J]. Ange-
事集多结构骨架一体化合物的合成及抗氧化性能研 wandte Chemie International Edition, 1998, 37: 2234-2237.
究提供了理论参考。 [18] Salunke D B, Yoo E, Shukla N M, et al. Structure-activity
relationships in human toll-like receptor 8-active 2,3-diamino-furo
[2,3-c]pyridines[J]. Journal of Medicinal Chemistry, 2012, 55(18):
参考文献：
8137-8151.
[1] Kuthyala S, Shankar M K, Nagaraja G K. Synthesis, single-crystal [19] Sharma A, Li H Y. A regioselective and high-yielding method for
X-ray, hirshfeld and antimicrobial evaluation of some new imidazo- formaldehyde inclusion in the 3CC Groebke-Blackburn-Bienaymé
pyridine nucleus incorporated with oxadiazole scaffold[J]. Chemistry reaction: One-step access to 3-aminoimidazoazines[J]. Cheminform,
Select, 2018, 3(45): 12894-12899. 2011, 2011(10): 1407-1412.
[2] Schaenzer A J, Wlodarchak N, Drewry D H, et al. A screen for kinase [20] Demjén A, Gyuris M, Wölfling J, et al. Facile synthesis of 1H-
inhibitors identifies antimicrobial imidazopyridine aminofurazans as imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach
specific inhibitors of the Listeria monocytogenes PASTA kinase Prka [J]. Beilstein Journal of Organic Chemistry, 2014, 10(1): 2338-2344.
[J]. Journal of Biological Chemistry, 2017, 292(41): 17037-17045. [21] Al-Tel T H, Al-Qawasmeh R A, Voelter W. Rapid assembly of
[3] Lee H, Kim S J, Jung K H, et al. A novel imidazopyridine pi3k polyfunctional structures using a one-pot five- and six-component
inhibitor with anticancer activity in non-small cell lung cancer cells sequential Groebke-Blackburn/Ugi/Passerini process[J]. European
[J]. Oncology Reports, 2013, 30(2): 863-869. Journal of Organic Chemistry, 2010, 2010(29): 5586-5593.
[4] Kamal A, Kumar G B, Nayak V L, et al. Design, synthesis and
biological evaluation of imidazopyridine/imidazopyrimidine-benzim- （下转第 377 页）