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 of the desired properties, while containing druglike chemical 
fragments. ChemGPS (chemical global positioning system) is a tool that combines 
these predefined rules and objects to provide a global drugspace map. The 
ChemGPS drugspace map coordinates are t-scores extracted via principal component 
analysis (PCA) from 72 descriptors that evaluate the above-mentioned rules on a 
total set of 423 satellite and core structures. Global ChemGPS scores describe 
well the latent structures extracted with PCA for a set of 8599 
monocarboxylates, a set of 45 heteroaromatic compounds, and for 87 alpha-amino 
acids. ChemGPS positions novel structures in drugspace via PCA-score prediction, 
providing a unique mapping device for the druglike chemical space. 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.