Druglike properties

Poor pharmacokinetics and toxicity are important causes of costly late-stage failures in drug development. It is generally recognized that, in addition to optimized potency and specificity, chemical libraries should also possess favorable ADME/Tox and druglike properties [77-80]. Assessment of druglike character is an attempt to decipher molecular features that are likely to lead to a successful in vivo and, ultimately, clinical candidate [81-83]. Many of these properties can be predicted before molecules are synthesized, purchased, or even tested in order to improve overall lead and library quality. 

The application of computational algorithms for compound filtering and clustering is routinely used to eliminate undesired structures on the basis of chemically reactive fimctionalities, predicted liabilities (e.g., frequent hitters, hERG, cyp450 and so forth), or druglike properties. Computational methods are also used to group compoimds on... 

Walters, W. P., Ajay, and Murcko, M. A. (1999) Recognizing molecules with druglike properties. Curr. Opin. Chem. Biol. 3, 384-7. 

Concurrent to the increasingly popular use of diverse libraries to sample chemical space and to provide chemical leads for various applications, the search for areas inside chemical space that are more promising for specific applications has also gained relevance (118-120). We will review the example of pharmaceutical research, where the so-called druglike properties of a molecule are the subject of frequent reports by various groups. 

Lipinski, C. A. Druglike properties and the causes of poor solubility and poor permeability,/. Pharmacol. Toxicol. Methods, 2000, 44, 235-249. 

Structure (518-522). In addition, the advent of combinatorial chemistry has focused modeling efforts on prioritizing compounds (523-528) for high throughput screening based on chemical diversity (529-531), druglike properties (532,533), predicted oral bioavailability (534,535), and so forth. 

Attain activity with druglike properties to achieve candidate selection (first time in humans). 

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