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Drug-like properties: guiding principles for design - or chemical prejudice?
Paul D Leeson1, Andrew M Davis2, John Steele1
1Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics, UK LE11 5RH.
Abstract:
The concepts of 'drug-like' and 'lead-like' chemical properties are having a major influence on the selection of compounds for high-throughput screening, and in the design of lead generation libraries. Medicinal chemists are recycling 'privileged' drug-like structures, whilst aiming to seek optimal physical properties for oral delivery. This approach biases the chemical profiles of compound screening collections towards known structures. Novel library synthesis, creating new chemical classes to address intellectual property, toxicity issues, and less chemically tractable targets, though considered risky, is warranted.:
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