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

ABSTRACT

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 (III_B) and HIV-2 (ROD) strains with an IC₅₀ ranging from >18 IC₅₀[µg/ml] to <100 IC₅₀[µg/ml]. Among them, compounds 4j and 4v were identified as the most promising compound for both types of HIV strains. (IC₅₀ = 18 µg/ml). Three compounds 4l, 4m, and 4p have been found potent anti-HIV 1 and 2 activity against MT-4 cells.

GRAPHICAL ABSTRACT

KEYWORDS:

• Anti-HIV activity
• highly functionalized pyrazolopyridone
• ketene dithioacetals
• MTT method

Additional information

Funding

Authors are thankful for financial assistance given under UGC-MiRP, New Delhi, Sanction No.: 47-605/13(WRO); Dated: 20/05/2014 and Shree M. & N. Virani Science College, Rajkot for providing central instrumentation & laboratory facilities and Prof. Pannecouque Rega Institute for Medical Research, KU Leuven, Belgium for providing Anti-HIV analysis.