CP-MLR/PLS directed quantitative structure-activity relationship study on the CDK8 inhibitory activity: The derivatives of naphthyridine and isoquinoline

The CDK8 and 7dF3 inhibition activity of naphthyridine isoquinoline derivatives have been quantitatively analyzed in terms Dragon descriptors. statistically validated quantitative structure-activity relationship (QSAR) models provided rationales to explain the activities these congeners. descriptors identified through CP-MLR analysis for inhibitory highlighted role sum topological distances between N..N (T(N..N)), distance/detour ring index order 6 (D/Dr06), aromatic ratio (ARR), number double bonds (nDB), 6-membered rings (nR06), sulphur atoms (nS), unsubstituted sp2 hybridized carbon (nCaH), aliphatic N hydrazines (nN-N), primary amines (nNH2Ph) certain atom centered fragments such as R--CH--R (C-024), X--CR..X (C-034), H attached C1(sp3)/C0(sp2) (H-047) RCO-N</>N-X=X (N-072) quantify actions. highest eigen value n.2 Burden matrix/weighted by atomic polarizabilites (BEHp2) Sanderson electronegativities weighted Geary autocorrelation lag 8 (descriptor GATS8e) also shown prevalence model activity. PLS has corroborated dominance Applicability domain revealed that suggested matches high quality parameters with good fitting power capability assessing external data all compounds was within applicability proposed were evaluated correctly. obtained from descriptor pool chosen is able nearly 74% variance observed titled compounds.