Synthesis and antimicrobial activity of new amino derivatives of pyrano

Annulated thienopyrimidine derivatives attracted big interest of the scientific community due to their broad spectrum of biological activities among which are the inhibition of phosphodiesterase, antiproliferative and antimicrobial activities. As a continuation of our studies on the synthesis and biological activity of fused thieno[3,2-d]pyrimidine derivatives, the goal of this paper is the synthesis and study of the properties of compounds containing different heterocycles such as fused thieno[2,3-b]pyridine and tetrazolo[1,5-c] pyrimidine in the same molecule. Thus, starting from the ethyl 1-amino-5-isopropyl-8,8-dimethyl-8,9dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate 1, efficient methods for obtaining new 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5] thieno[3,2-d]pyrimidines 6 and thieno[2,3-e]tetrazolo[1,5-c]pyrimidine 8 are described. The spectroscopic results showed that compound 8 in the solid state is exclusively in the tetrazolo tautomeric form, while in solution an azide-tetrazole equilibrium is present 8A/T. The possible antimicrobial activity of newly synthesized compounds against some gram-positive and gram-negative bacilli strains has been evaluated. The biological tests evidenced that some of them showed promising antimicrobial activity. Two compounds showed similar activity to the one of the used reference drug. The study of structure-activity relationships revealed that the activity of a compound depends mostly on the nature of substituent RR. According to the predicted docking studies our compounds could be DnaG inhibitors.

[1]  S. Sirakanyan,et al.  Synthesis and Anticonvulsant Activity of 7(8)-Amino Derivatives of Condensed Thieno[3,2-d]Pyrimidines , 2016, Pharmaceutical Chemistry Journal.

[2]  D. Spinelli,et al.  The azide/tetrazole equilibrium: an investigation in the series of furo- and thieno[2,3-e]tetrazolo[3,2-d]pyrimidine derivatives , 2016 .

[3]  G. M. Wilson,et al.  Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines. , 2014, Bioorganic & medicinal chemistry.

[4]  S. Sirakanyan,et al.  Synthesis and Neurotropic Activity of 8-Amino Derivatives of Condensed Thieno[3,2-d]- and Furo[3,2-d]Pyrimidines , 2014, Pharmaceutical Chemistry Journal.

[5]  M. N. Nasr,et al.  Synthesis and antitumor activity of new pyrido[2,3-d]pyrimidine derivatives , 2012, Medicinal Chemistry Research.

[6]  N. M. Rateb.  Convenient Synthesis and Antimicrobial Evaluation of Multicyclic Thienopyridines , 2008 .

[7]  R. S. Sackett,et al.  Synthesis of 4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamides with broad-spectrum human herpesvirus polymerase inhibition. , 2008, Bioorganic & medicinal chemistry letters.

[8]  Jason A. Wiles,et al.  Small molecule inhibitors of E. coli primase, a novel bacterial target. , 2007, Bioorganic & medicinal chemistry letters.

[9]  E. A. Al-Taifi,et al.  SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME NEW PYRIDO[3′,2′:4,5]THIENO[3,2-d]- PYRIMIDINE DERIVATIVES , 2004 .

[10]  V. Litvinov.  Thienopyrimidines: synthesis, properties, and biological activity , 2004 .

[11]  I. A. Dzhagatspanyan,et al.  Derivatives of Condensed Thienopyrimidines: Synthesis and Neurotropic Activity of New Pyrano[4′,3′:4,5]thieno[3,2-e]triazolo[3,4-b]pyrimidine Derivatives , 2004, Pharmaceutical Chemistry Journal.

[12]  E. A. Bakhite,et al.  Synthesis and Reactions of New Thienopyridines, Pyridothienopyrimidines and Pyridothienotriazines. , 2003 .

[13]  Asit K Chakraborti,et al.  3D-QSAR studies on thieno[3,2-d]pyrimidines as phosphodiesterase IV inhibitors. , 2003, Bioorganic & medicinal chemistry letters.

[14]  Detlef D. Leipe,et al.  Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. , 1998, Nucleic acids research.

[15]  E. Lanka,et al.  Domain structure of phage P4 alpha protein deduced by mutational analysis , 1995, Journal of bacteriology.