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

Abstract

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, (1)H, (13)C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.

Synthesis and Biological Activity of Some Nucleoside Analogs of 3-Cyanopyridin-2- one

“…Relative content percentages of GST, GSH-Rd and MDA in untreated and treated carcinoma cells.cytotoxic and anticancer cell growth activities. The results indicated that all of the tested compounds exhibited antibacterial effects, whereas only the sugar-containing compounds(13)(14)(15)(16), which had the highest activity against all of the target organisms, exhibited activity against the target fungal strain and this may attributed to the main nucleus of the synthesized compounds (cyanopyridine) and this also means that the sugar moieties increases the antimicrobial effect. The MIC values indicated that the glycosyl compounds (13-16) had the lowest MIC values against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Salmonella typhimurium) and the fungal strain Fusarium oxysporum, whereas the other compounds had moderate MIC values against all of the tested strains.…”

“…The inhibition zones of the starting compound (1), pyridinebased derivatives (2-12 and 17) and nucleoside analogs (13)(14)(15)(16) are presented in Table 2. The presented results indicated that all of the tested compounds exhibited antibacterial effects, whereas only compounds 13-16 exhibited activity against the target fungal strains.…”

“…Pyridine derivatives exhibited strong cytotoxicity against several human cancer cells [4][5][6][7]; displayed antidepressant [8], cardiotonic [8] and antimalarial [9] activities; inhibited insulin-like growth factor-1 receptor (IGF-1R) kinase [10], anaplastic lymphoma kinase (ALK) [11], hepatitis B virus (HBV) [12], farnesyltransferase [13] and HCV NS5B polymerase [14] and displayed antimicrobial [15][16][17][18][19] and antimycobacterial activities [20]. The non-glycosidic cardiotonic agent milrinone [21,22] and other pyridine derivatives proved to be active against herpesviruses and the human immunodeficiency virus [23][24][25][26].…”

O‐Glycosylation/Alkylation and Antimicrobial Activity of 4,6‐Diaryl‐2‐Oxonicotinonitrile Derivatives

“…The anomeric protons in glcycosides 2a , 2b ; 4a , 4b ; and 6a appeared in 1 H NMR spectra at δ = 6.57–6.84 ppm as doublet with coupling constants J = 8.0 or 8.4 Hz, which explains the β ‐configuration. The deacetylation of O ‐glycosides 2a , 2b ; 4a , 4b ; and 6a via the procedure described herein led to the free glycosides 3a , 3b ; 5a , 5b ; and 7a , respectively (Scheme ). The IR spectra of the free O ‐glycosides showed the absence of acetoxy carbonyl groups and presence of bands at 3398–3420 cm −1 corresponding to free OH groups.…”

“…As a part of our ongoing program for the synthesis of 2‐oxopyridinecarbonitrile derivatives as potential biologically active compounds [18‐20], herein, we reported on the glycosylation and alkylation of 2‐oxo‐4‐aryl‐6‐phenanthrenyl‐1,2‐dihydropyridine‐3‐carbonitrile 1a , 1b derivatives and their evaluation as potential antimicrobial agents.…”