Plots of molecular weight vs. LogP vs. Fsp3(a), and a Principle Component Analysis (b) of the collection using these 3 descriptors is an effective way to represent the diversity and occupation of chemical space by our collection.
Comparison plots of our collection vs. commercial collections, show good overlap with known FDA approved drugs (c) and Enamine’s Hit Locator Library (d), as well as showing healthy diversity in lesser explored chemical space.
A powerful molecular descriptor of 3D character is the fraction of sp3-hybridised carbons / total number of carbons (Fsp3) (e). Increasing the saturation and the 3D complexity of a compound is likely to increase the chance of success in drug discovery programmes.
A Principal Moments of Inertia (PMI) Plot (f) show our collection populates areas of chemical space which are increasingly spherical in shape, moving away from ‘traditional’ flatter 2D molecules which have dominated drug discovery.
The focus on diversity, maximising occupancy of chemical space and favourable physiochemical properties is clearly demonstrated from the plots below of the physical collection, enriched with iDESIGN project compounds.