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Estimation of Aqueous Solubility of Organic Compounds with QSPR Approach

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Abstract

Purpose. To derive a QSPR model for estimation of aqueous solubility of organic compounds.

Methods. Solubility data for 930 diverse compounds was investigated with principal component regression analysis. This set of compounds consists of pharmaceuticals, pollutants, nutrients, herbicides, and pesticides. The diversity of this collection was analyzed using MACCS fingerprint and BCUT chemistry space.

Results. The training set of the solubility data is as diverse as the Available Chemicals Directory, and more diverse than the MDL Drug Data Report. Forty-six molecular descriptors were screened using a genetic algorithm. A QSPR model with a squared correlation coefficient (r2) of 0.92, a root mean square error of 0.53 log molar solubility (log Sw), an average absolute estimation error of 0.36 log Sw, and a cross-validated q2 of 0.91 was derived. The QSPR model was validated with a test set of 249 compounds not included in the training set. The absolute estimation error for the test set of compounds was 0.39 log Sw.

Conclusions. A highly predictive QSPR model for estimating aqueous solubility was derived and validated. This model can be used to estimate aqueous solubility for virtual screening and combinatorial library design.

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Authors and Affiliations

  1. Computer-Aided Drug Discovery, Pharmacia, 301 Henrietta Street, Kalamazoo, Michigan, 49007

    Hua Gao, Veerabahu Shanmugasundaram & Pil Lee

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  1. Hua Gao
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  2. Veerabahu Shanmugasundaram
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  3. Pil Lee
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Correspondence to Hua Gao.

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Gao, H., Shanmugasundaram, V. & Lee, P. Estimation of Aqueous Solubility of Organic Compounds with QSPR Approach. Pharm Res 19, 497–503 (2002). https://doi.org/10.1023/A:1015103914543

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