Pyrrolo[2,3]quinoxalines in attenuating cytokine storm in COVID-19: their sonochemical synthesis and / assessment.

In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-substituted pyrrolo[2,3-]quinoxalines for this purpose because of their potential inhibitory properties of PDE-4 / TNF-α. Moreover, several of these compounds appeared to be promising when assessed for their binding affinities docking into the -terminal RNA-binding domain (NTD) of -protein of SARS-CoV-2. A rapid and one-pot synthesis of this class of molecules was achieved the Cu-catalyzed coupling-cyclization-desulfinylation of 3-alkynyl-2-chloroquinoxalines with -butyl sulfinamide as the ammonia surrogate under ultrasound irradiation. Most of these compounds showed good to significant inhibition of TNF-α establishing a SAR (Structure Activity Relationship) within the series. One compound e.g. was identified as a promising hit for which the desirable ADME and acceptable toxicity profile was predicted .