Chemography: the art of navigating in chemical space.

TLDR: ChemGPS scores are comparable across a large number of chemicals and do not change as new structures are predicted, making this tool a well-suited reference system for comparing multiple libraries and for keeping track of previously explored regions of the chemical space.

Abstract: Combinatorial chemistry needs focused molecular diversity applied to the druglike chemical space (drugspace). A drugspace map can be obtained by systematically applying the same conventions when examining the chemical space, in a manner similar to the Mercator convention in geography:  Rules are equivalent to dimensions (e.g., longitude and latitude), while structures are equivalent to objects (e.g., cities and countries). Selected rules include size, lipophilicity, polarizability, charge, flexibility, rigidity, and hydrogen bond capacity. For these, extreme values were set, e.g., maximum molecular weight 1500, calculated negative logarithm of the octanol/water partition between −10 and 20, and up to 30 nonterminal rotatable bonds. Only S, N, O, P, and halogens were considered as elements besides C and H. Selected objects include a set of “satellite” structures and a set of representative drugs (“core” structures). Satellites, intentionally placed outside drugspace, have extreme values in one or several o...