Molecular descriptors in modeling of TNF-α converting enzyme (TACE) inhibition activity of 2-(2-aminothiazol-4-yl)pyrrolidine-based tartrate diamides

摘要

A quantitative structure-activity relationship (QSAR) study has been carried out on a new series of tartrate-based compounds to explain their TNF-a converting enzyme (TACE) inhibition activity in terms of chemometric descriptors. The 2D-descriptors, identified through combinatorial protocol in multiple linear regression (CP-MLR) analysis, have highlighted the role of either polarizability or van dcr Waals type of interaction for (±)-congeners of the series. On the other hand, the atomic masses and atomic Sanderson electronegativities weighted descriptors have played significant role in addressing TACE inhibition activities of remaining compounds of the series. A few potential compounds of tartrate scaffold have also been suggested for further investigation. PLS analysis has further corroborated the dominance of the CP-MLR identified descriptors. Applicability domain analysis has revealed that the suggested models have acceptable predictability. All the compounds, including suggested congeners, arc within the applicability domain of the proposed models and are evaluated correctly.