Lead-like hits

Wunberg, T., Hendrix, M., Hillisch, A., Lobell, M., Meier, H., Schmeck, C., Wild, H., Hinzen, B. Improving the hit-to-lead process data-driven assessment of drug-like and lead-like screening hits. Drug Discov. Today 2006, 11, 175-80. 

In parallel, hits are nominated from the group of actives, and chemical optimization is begun, to generate optimized leads. Ideally, the biased library consists of lead-like compounds and allows an efficient, short optimization program. We can anticipate that this parallel approach in chemical biology will lead to time reduction by 3.5 years as compared to the classical linear approach. 

Hard filters are the most stringent in-silico filters and are used to shape the property profile of screening or combinatorial libraries and to prune hit lists from primary screening. They are derived from ID and 2D molecular properties (molecular weight, number of H-bond donors/acceptors, number of rotatable bonds, and so forth) and, as is described below, they are commonly used to reduce the number of false positive hits and to favor lead-like or drug-like chemotypes. 

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