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QSPR with extended topochemical atom (ETA) indices. 4. Modeling aqueous solubility of drug like molecules and agrochemicals following OECD guidelines

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Abstract

Aqueous solubility is the property of utmost interest for predicting the behavior of chemical compounds inside body, since water serves as the most ubiquitous component of any living cell. Predictive quantitative structure–property relationship models on aqueous solubility try to explore the essential chemical information of molecules that control their dissolution ability. Considering the importance of solubility controlling the absorption, distribution, metabolism, excretion, and toxicity properties of drug and other such chemicals, attempts were made to develop predictive models following OECD guidelines on aqueous solubility of a large set (N = 565) of diverse drug, drug like compounds, and agrochemicals with extended topochemical atom (ETA) indices using suitable chemometric tools. Because of the prime involvement of hydrophobicity in solubilization of structurally complex and crystalline organic compounds, computed lipophilicity parameter ClogP was used. Models were also developed using various other non-ETA descriptors. Additional attempt was made to build models employing ETA, non-ETA, and ClogP parameters. All the models were subjected to rigorous statistical validation using multiple strategies and encouraging results were obtained for internal, external, and overall validation of the models. Comparative analysis performed on the prediction set (test set) using general solubility equation, and the best model developed here with ETA and ClogP parameters demonstrated better predictive potential of the latter model.

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Acknowledgments

Financial assistance from the Council of Scientific and Industrial Research, Government of India, New Delhi in the form of a fellowship to R.N.D. is gratefully acknowledged.

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  1. Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India

    Rudra Narayan Das & Kunal Roy

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Correspondence to Kunal Roy.

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Das, R.N., Roy, K. QSPR with extended topochemical atom (ETA) indices. 4. Modeling aqueous solubility of drug like molecules and agrochemicals following OECD guidelines. Struct Chem 24, 303–331 (2013). https://doi.org/10.1007/s11224-012-0080-5

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