Identification of prodigious and under-privileged structural features for RG7834 analogs as Hepatitis B virus expression inhibitor

Abstract

In the present work, QSAR (quantitative structure−activity relationship) analysis has been executed for RG7834 analogs. RG7834 is a first-in-class selective and orally available dihydroquinolizinone (DHQ)-based small molecule Hepatitis B virus expression inhibitor. OECD’s guidelines have been followed for developing multiple QSAR models for Hepatitis B virus expression inhibitory activity of 73 RG7834 analogs. The present multiple QSAR models are not only easily interpretable but possess high external predictive ability, as well. These are effective in the recognition of many privileged and underprivileged molecular descriptors, which could be very valuable for the use of these models by the experts and nonexperts of QSAR in future optimizations. The models satisfy threshold values for many fitting, internal and external validation parameters, such as R2 = 0.83, Q2 = 0.80, CCCext = 0.88, etc., thereby demonstrating good external predictive ability of the models. The multiple QSAR and pharmacophoric models successfully identified a good number of important positively and negatively related structural features of RG7834 analogs that govern their Hepatitis B virus expression inhibitory activity. The results could be very beneficial to synthetic/medicinal chemists for future alterations of RG7834 analogs as better drug candidates.