2.3 Variations of Filtering

Different types of filters are appropriate under different circumstances. Very early in a project, when little or no SAR is available, very strict drug-like filters can be applied. This prevents a project team from spending chemistry resources pursuing difficult compounds that may not be modifiable to introduce appropriate properties. However, when considering compounds for purchase for HTS, different filters can be applied. Oprea, et al, pointed out that the best molecules for initial HTS are smaller and less functionalised than drugs, but with some activity [4]. Therefore, strict lead-like filters can be applied to ensure that hits identified from HTS have sufficient "room" for elaboration into (usually larger and more highly functionalised) leads. However, when SAR suggests that particular compounds or series may yield valuable information, filtering criteria can be loosened, because the secondary screens (QSAR models, similarity to known actives) that are being applied are effective in detecting useful compounds. Reflecting back on the medical analogy, this is the case where an improved primary screen with a dramatically improved false-positive rate (say 1 in 100,000) can be safely applied to a larger population without terrible effects on the positive-predictive value. In the Filter program, we provide examples of both "heavy" (restrictive) and "light" (lenient) filters.

				FILTER Database preparation Property calculation

				FILTER Database preparation Property calculation