新型1,2,3-三唑类化合物的合成及抗菌构效关系
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摘要
根据活性基团拼接原理,以4-取代-苯胺为原料,经重氮化、关环和缩合反应合成了17个化合物1-(4-取代苯基)-5-取代苯基亚氨基-4-取代-1,2,3-三唑(7a～7c和13a～13d)和1-(4-取代苯基)-5-取代苄基氨基-4-取代-1,2,3-三唑(5a～5c,10a～10c和14a～14d),其中化合物5a～5c,7b,7c,10a,10c,13b～13d和14b～14c为新化合物,对所制备化合物的结构进行了表征.生物活性测试结果表明,所有化合物均表现出一定的抑菌活性,对大肠杆菌的抑菌活性均优于氟康唑;化合物7a和10c对金黄色葡萄球菌的抑制活性明显优于氟康唑;而化合物13a和13d则对白色念球菌表现出良好的抑制活性,与三氯生相当.
According to active groups combination principle,seventeen compounds 1-(4-substituted phenyl)-5-substituted phenylbutyronitrile-4-substituted 1,2,3-triazoles(7a—7c,13a—13d) and 1-(4-substituted phenyl)-5-substituted benzylamino-4-substituted 1,2,3-triazoles(5a—5c,10a—10c and 14a—14d) were designed and synthesized through diazotization,cyclization and condensation reactions from 4-substituted aniline,while compounds 5a—5c,7b,7c,10a,10c,13b—13d and 14b—14d have never been reported.Their structures were confirmed by IR,1H NMR and 13C NMR.The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities,especially,they all exhibited better activities against Escheri-chia coli than fluconazole,while against Staphylococcus aureus,compounds 7a and 10c were more effective than fluconazole,and compounds 13a and 13c were as good as triclosan against Monilia albican.
According to active groups combination principle,seventeen compounds 1-(4-substituted phenyl)-5-substituted phenylbutyronitrile-4-substituted 1,2,3-triazoles(7a—7c,13a—13d) and 1-(4-substituted phenyl)-5-substituted benzylamino-4-substituted 1,2,3-triazoles(5a—5c,10a—10c and 14a—14d) were designed and synthesized through diazotization,cyclization and condensation reactions from 4-substituted aniline,while compounds 5a—5c,7b,7c,10a,10c,13b—13d and 14b—14d have never been reported.Their structures were confirmed by IR,1H NMR and 13C NMR.The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities,especially,they all exhibited better activities against Escheri-chia coli than fluconazole,while against Staphylococcus aureus,compounds 7a and 10c were more effective than fluconazole,and compounds 13a and 13c were as good as triclosan against Monilia albican.
引文
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[3]Velaquez S.,Alvarez R.,Perez C.,Gogo F.,De C.,Balzarini J.,Carmarasa M.J.,Antiviral Chem.Chemother,1998,9(6),481—489
[4]Dalip K.,Buchi R.V.,Anil K.,Deendayal M.,Rakesh T.,Keykavous P.,Bioorg.Med.Chem.Lett.,2011,21,449—452
[5]Dabak K.,Sezer O.,Akar A.,Anac O.,Eur.J.Med.Chem.,2003,38,215—218
[6]Zhang S.S.,Wan J.,Li X.M.,Li C.L.,Xu L.Z.,Chem.Res.Chinese Universities,2007,23(1),120—124
[7]Kelley J.L.,Koble C.S.,Davis R.G.,McLean E.W.,Soroko F.E.,Cooper B.R.,J.Med.Chem.,1995,38,4131—4134
[8]Huang Y.T.,Ouyang X.M.,Okamura T.,Li Y.Z.,Sun W.Y.,Ueyama N.,Chin.J.Inorg.Chem.,2005,21(10),1479—1752(黄玉婷,欧阳兴梅,岡村高明,李一志,孙为银,上山寭一.无机化学学报,2005,21(10),1479—1752)
[9]Genin M.J.,Allwine D.A.,Anderson D.J.,Barbachyn M.R.,Emmert D.E.,Garmon S.A.,Graber D.R.,Grega K.C.,Hes-ter J.B.,Hutchinson D.K.,Morris J.,Reischer R.J.,Ford C.W.,Zurenko G.E.,Hamel J.C.,Schaadt R.D.,Stapert D.,Yagi B.H.,J.Med.Chem.,2000,43,953—970
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[11]Wang B.L.,Shi Y.X.,Ma Y.,Liu X.H.,Li Y.H.,Song H.B.,Li B.J.,Li Z.M.,J.Agric.Food Chem.,2010,58,5515—5522
[12]Liliana M.,Finkielsztein E.F.,Castro L.E.,Fabian L.E.,Moltrasio G.Y.,Eur.J.Med.Chem.,2008,43,1767—1773
[13]Zhao Q.,Lu J.R.,Xin C.W.,Bao X.R.,Gao H.Y.,Zhao X.,Li S.,Rui T.T.,Chin.J.Org.Chem,2011,32(12),2806—2811(赵芡,卢俊瑞,辛春伟,鲍秀荣,高海燕,赵旭,李莎,芮甜甜.有机化学,2011,32(12),2806—2811)
[14]Zhao X.,Lu J.R.,Xin C.W.,Lu B.W.,Bao X.R.,Li J.F.,Liu Y.,Yang X.Y.,Yuan Y.,Chem.Res.Chinese Universities,2012,28(3),1—6
[15]Mu M.M.,Lu B.W.,Lu J.R.,Xin C.W.,Ji D.,Li J.F.,Bao X.R.,Chin.J.Org.Chem.,2012,32,1101—1107(穆曼曼,卢博为,卢俊瑞,辛春伟,戢丹,李建发,鲍秀荣.有机化学,2012,32,1101—1107)
[16]Bucking J.,Dictionary of Organic Compunds,5th Ed.,Chapman and Hall Press,New York,1982,808
[17]Charansingh G.,Ganesh J.,Mohammad S.,Rajesh K.,Anant G.,Deepak N.,Mahendra S.,Bioorg.Med.Chem.Lett.,2008,18,6244—6247
[18]Cao Z.P.,Dong H.S.,Quan B.,J.Chinese Chem.Soc.(Taipei,Taiwan),2008,55(4),761—767
[19]Chen M.D.,Guo S.L.,Zheng Y.F.,Chen L.,Tang F.,Hua W.Y.,Heterocyclic Communications,2005,11(4),285—290
[20]Eugene L.,Tai S.C.,Rsmachandr C.N.,Presented in Part at the 128th National Meeting of the American Chemical Society,Minneapo-lis,1955
[21]Alfred D.,Jurgen H.,Eur.J.Inorg.Chem.,1960,93(16),2001—2010