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Abstract

Pirfenidone is used as antifibrotic agent for treatment of liver and lung fibrosis. The pirfenidone has problem of high dose requirement, low efficacy and short half-life. The present communication deals with the quantitative structure activity relationship (QSAR) and docking analysis on the series of 5-substituent-2(1H)-pyridone derivatives for identification of structural features which governs the pharmacodynamic and pharmacokinetic activities of 5-substituent-2(1H)- pyridone derivatives as antifibrotic agents. Best QSAR model with r2 = 0.8687 and q2 = 0.6278, developed by multiple linear regression (MLR) method has showed that bulky substituent’s which are capable imparting electron withdrawing capacity to the molecules or making electronegative potential will be increasing the antifibrotic potential of 5-substituent-2(1H)-pyridone derivatives. The results of docking studies proved that designing of potent molecules with improved pharmacokinetics would be possible as sites of interactions are different for antifibrotic activity (mitogen activated protein kinase p 38 gamma) and metabolism (Cytochrome P 4501A2).

Keywords

Pyridone Pirfenidone QSAR Metabolism Multiple linear regression Protein kinase

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Jadhav, S., Choudhari, P., & Bhatia, M. (2016). QSAR Screening of 5-Substituent-2(1H)- pyridone Derivatives with Improved Pharmacokinetic Parameters. Asian Journal of Organic & Medicinal Chemistry, 1(3), 97–100. https://doi.org/10.14233/ajomc.2016.AJOMC-P28
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