Novel nucleosides as potent influenza viral inhibitors.
Influenza virus infection constitutes a significant health problem in need of more effective therapies. We have recently identified ((2R,3S,4R,5R)-3-acetoxy-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl) methyl benzoate (18c) as a potent influenza virus inhibitor. We now here report the synthesis and evaluation of a series of C-3' modified ribose nucleosides. These novel compounds were prepared, primarily by taking known ((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (1) and converting it in to C-3 keto sugar (7), reacting C-3 keto group with methyl magnesium bromide, followed by coupling these sugars with purine and pyrimidine bases. Anti influenza viral activity was determined by screening against both A and B viral strains.
Vedula
Manohar Sharma
MS
New Drug Discovery, Hetero Research Foundation, Hetero Drugs Limited, Plot No. 80 & 81, APIE, Balanagar, Hyderabad, Andhra Pradesh 500 037, India. sharmavm@heterodrugs.com
Jennepalli
Sreenu
S
Aryasomayajula
Ratnakar
R
Rondla
Subhash Reddy
SR
Musku
Madanmohan Reddy
MR
Kura
Rathnakar Reddy
RR
Bandi
Parthasaradhi Reddy
PR
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D009981:Influenza B virus / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D011684:Purine Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides