Synthesis of Acyclovir and HBG Analogues Having Nicotinonitrile and Its 2-methyloxy 1,2,3-triazole

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, 1H, 13C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.

[1]  J. Lavandera,et al.  In vitro absorption of 4(1H)-pyridone antimalarial derivative and its pro-drug using a Caco-2 model , 2010 .

[2]  N. Sultana,et al.  Sparfloxacin-metal complexes as antifungal agents - Their synthesis, characterization and antimicrobial activities , 2010 .

[3]  A. Ghose,et al.  Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. , 2010, Bioorganic & medicinal chemistry.

[4]  G. Trainor,et al.  Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one. , 2010, Bioorganic & medicinal chemistry letters.

[5]  A. Abadi,et al.  Discovery of colon tumor cell growth inhibitory agents through a combinatorial approach. , 2010, European journal of medicinal chemistry.

[6]  Zhiliang Lv,et al.  Synthesis and anti-HBV activity of novel 5-substituted pyridin-2(1H)-one derivatives , 2010 .

[7]  E. De Clercq,et al.  Practical and efficient synthesis of pyrano[3,2-c]pyridone, pyrano[4,3-b]pyran and their hybrids with nucleoside as potential antiviral and antileishmanial agents. , 2010, Bioorganic & medicinal chemistry letters.

[8]  J. Engels,et al.  Microwave-assisted click chemistry: synthesis of mono and bis-1,2,3-triazole acyclonucleoside analogues of ACV via copper(I)-catalyzed cycloaddition , 2009 .

[9]  A. Moustafa,et al.  Synthesis and Antimicrobial Activity of Some S-β-D-Glucosides of 4-Mercaptopyrimidine , 2009, Nucleosides, nucleotides & nucleic acids.

[10]  A. Moustafa,et al.  Synthesis and Antibacterial Activity of Some Glucosyl- and Ribosyl-Pyridazin-3-ones , 2009, Nucleosides, nucleotides & nucleic acids.

[11]  F. El-Mariah,et al.  Synthesis and Antimicrobial of Some Novel-5-carbomethoxy-2-pyridone Derivatives Containing Sulfonamide Moiety , 2008 .

[12]  A. Moustafa,et al.  Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides , 2008, Nucleosides, nucleotides & nucleic acids.

[13]  Jun Wu,et al.  A Highly Efficient and Selective Synthesis of 1,2,3-Triazole Linked Saccharide Nucleosides Via “Click Chemistry” , 2008, Nucleosides, nucleotides & nucleic acids.

[14]  E. Degerman,et al.  Re-discovering PDE3 inhibitors--new opportunities for a long neglected target. , 2007, Current topics in medicinal chemistry.

[15]  E. Garvey,et al.  Synthesis and HIV-integrase strand transfer inhibition activity of 7-hydroxy[1,3]thiazolo[5,4-b]pyridin-5(4H)-ones. , 2006, Bioorganic & medicinal chemistry letters.

[16]  A. Abdel-Aziz,et al.  Lewis acid-promoted transformation of 2-alkoxypyridines into 2-aminopyridines and their antibacterial activity. Part 2: Remarkably facile C-N bond formation. , 2005, Bioorganic & medicinal chemistry.

[17]  R. Henry,et al.  Synthesis of 1H-pyridin-2-one derivatives as potent and selective farnesyltransferase inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[18]  A. M. Attia,et al.  An approach to acyclo-3-deazapyrimidine S-nucleosides via 3,5-dicyano-2(1H)-pyridinethiones , 2003 .

[19]  E. De Clercq,et al.  SYNTHESIS AND ANTI-HIV ACTIVITY OF NEW MODIFIED 1,2,3-TRIAZOLE ACYCLONUCLEOSIDES , 2001, Nucleosides, nucleotides & nucleic acids.

[20]  R. Boggia,et al.  3-Acetyl-5-acylpyridin-2(1H)-ones and 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones: synthesis, cardiotonic activity and computational studies. , 1999, Farmaco.

[21]  E. Ashry,et al.  Acyclonucleosides. Part 3. tri-, tetra-, and pentaseco-Nucleosides , 1998 .

[22]  L. Botana,et al.  Synthesis and antihistaminic activity of 2-guanadino-3-cyanopyridines and pyrido[2,3-d]-pyrimidines. , 1997, Bioorganic & medicinal chemistry.

[23]  E. Ashry,et al.  Acyclonucleosides. Part 2. diseco‐Nucleosides , 1997 .

[24]  C. Peinador,et al.  A ready one-pot preparation for 7-oxa(or thia)-3,4,6-triazabenz[d,e]anthracene and 7-oxa-3,4,6,9-tetrazabenz[d,e]anthracene derivatives , 1996 .

[25]  Baldev Singh,et al.  Facile and Novel Synthesis of 1,6-Naphthyridin-2(1H)-ones. , 1991 .

[26]  Baldev Singh,et al.  A facile and novel synthesis of 1,6‐naphthyridin‐2(1H)‐ones , 1990 .

[27]  Chris P. Miller,et al.  A simplified route to a key intermediate in the synthesis of the Chinese nootropic agent huperzine A , 1990 .

[28]  Alan R. Katritzky,et al.  Handbook of heterocyclic chemistry , 1985 .