Discovery of Novel Tetrahydropyrido-Pyrazole based Cathepsin S Inhibitors: Implications of Two Dimensional Quantitative Structure Activity Relationship Analysis

The anti-arthritic activity of cathepsin S enzyme has been acknowledged and regarded as an emerging target for the development novel therapeutic agents treatment various autoimmune disorders other inflammatory diseases. Two dimensional-quantitative structure-activity relationships have performed on a series tetrahydropyrido-pyrazole nucleus using TSAR 3.3. Attempts made to derive comprehend correlation between biological (dependent variable) descriptors (independent variables). study was 268 compounds (data set) by division into training test set random selection method. 179 generated final quantitative relationship model with leave-out one row method cross-validation evaluate predictive ability model. most significant n=179, regression coefficient (0.851), (0.725), cross-validated (0.709), standard error (0.349), Fischer statistic value (114.706) developed multiple linear analysis. For partial least squares, statistical significance 0.988 fraction variance explained 0.723 were observed. A comparable squares (0.723) neural (0.731) indicated good internal predictability External validation provided values 0.708 0.706 regressions analysis respectively. Quantitative importance hydrophobic (log P (substituent 1)), topological (kier chi 5 (path) index (whole molecule)), electronic (bond dipole moment 5)) (dipole Z component 1)) Cathepsin inhibitors. This will be effective in designing more potent