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Synthesis of New Derivatives of Heterocyclic Systems Containing Triazolopyrimidine, thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b] thiazine Moiety Showing Promising Antimicrobial Activity

[ Vol. 22 , Issue. 26 ]

Author(s):

Samvel N. Sirakanyan*, Domenico Spinelli*, Athina Geronikaki, Viktor A. Kartsev, Elmira K. Hakobyan and Anush A. Hovakimyan   Pages 2576 - 2588 ( 13 )

Abstract:


Background and Objective: Continuing our research in the field of heterocyclic compounds and exploiting our experience in the synthesis of pyridothieno(furo)[3,2- d]pyrimidine derivatives decorated by suitable reactive groups (in turn able to give rise to the formation of new heterocyclic rings), we now carried out a research with the aim of building in different position of the pyrimidine some new hetero-rings: the 1,3,4-triazole, thiazole and thiazine. Moreover their possible antimicrobial activity against some grampositive and gram-negative bacilli strains has been evaluated.

Methods: Starting from the hydrazino derivative of pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines 2 (7) by reflux with triethyl orthoformate or formic acid, some substituted isomeric pyrido[3',2':4,5]thieno(furo)[2,3-e][1,2,4]triazolopyrimidines 3 and 4 (10) have been synthesized. By alkylation of compounds 8 with alkyl dichlorides, the cyclization to a thiazoline or to a thiazine ring on the [a] side of the pyrimidine ring occurs, with the formation of the new pentacyclic systems: pyrido[3',2':4,5]thieno[ 3,2-d][1,3]thiazolo[3,2-a]pyrimidin-7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1- b][1,3]thiazin-7(8)-ones 16.

Results: 11-Alkyl(aryl)-8,8-dimethyl-7,10-dihydro-8H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4] triazolo[4,3-c]pyrimidines 3 gave a Dimroth rearrangement in acidic media. It was observed that the cyclization of compounds 7 and 8 occurred linearly with the expected formation of pyrido[3',2':4,5]thieno(furo)[3,2- d][1,2,4]triazolo[4,3-a]pyrimidin-7(8)-ones 10 and pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin- 7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-7(8)-ones 16: that is triazole, thiazole and thiazine ring condensation occurs at the [b] side of the pyrimidine ring. During the alkylation of compounds 7, the unusual cleavage of the hydrazino group took place with the formation of 8(9)- methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12.

Conclusion: The synthesis of some new ‘complex’ pentaheterocyclic systems containing triazolopyrimidine, thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b]thiazine moiety based on the pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines is described. During the alkylation of 9(10)-hydrazinopyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidin-7(8)-ones 7 an unexpected cleavage of the hydrazino group has been observed with the formation of 8(9)-methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12. Biological tests on the newly synthesized compounds evidenced that some of them showed promising antimicrobial activity.

Keywords:

Triazolopyrimidine, thiazolo[3, 2-a]pyrimidine, pyrimido[2, 1-b]thiazine, cyclization, alkylation, antimicrobial activity.

Affiliation:

Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L.Mnjoyan, Armenia 0014, Yerevan, Ave. Azatutyan 26, Dipartimento di Chimica G. Ciamician, Alma Mater Studiorum-Universita di Bologna, Via F. Selmi 2, Bologna 40126, Aristotle University of Thessaloniki, School of Pharmacy, Thessaloniki 54124, InterBioScreen, a/ya 218, Moscow 119019, Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L.Mnjoyan, Armenia 0014, Yerevan, Ave. Azatutyan 26, Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia, Institute of Fine Organic Chemistry of A.L.Mnjoyan, Armenia 0014, Yerevan, Ave. Azatutyan 26

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