Facile synthesis of highly functionalized novel pyrazolopyridones using oxoketene dithioacetal and their anti-HIV activity

A series of novel 3-amino-4,5-dihydro-6-methyl-4-oxo-N-aryl-1H-pyrazolo[4,3-c]pyridine-7-carboxamide have been synthesized starting from various oxoketene dithioacetals. The cyclocondensation reaction of 2-(bis(methylthio)methylene)-3-oxo-N-arylbutanamide 2a-w with cyanoacetamide using NaOiPr as base under reflux condition afforded novel highly functionalized pyridone 3a-w derivatives. Further, [3+2] cyclocondensation reaction of pyridones with hydrazine in the presence of alcohol was yielded pyrazolopyridones (23 nos) 4a-w with excellent yields. All newly synthesized compounds were evaluated for in vitro anti-HIV activity using MTT method. Most of these compounds have showed moderate to potent activity against HIV-1 (IIIB) and HIV-2 (ROD) strains with an IC50 ranging from >18 IC50[mu g/ml] to <100 IC50[mu g/ml]. Among them, compounds 4j and 4v were identified as the most promising compound for both types of HIV strains. (IC50=18 mu g/ml). Three compounds 4l, 4m, and 4p have been found potent anti-HIV 1 and 2 activity against MT-4 cells. [GRAPHICS] .