The discovery of a new drug lead usually starts with identifying a hit compound, e.g., by screening an extensive chemical database with experimental or virtual high throughput screening (HTS). Then, the hit optimization -the more expensive and laborious stage -attempts modifications of the structure to maximize the desired biological activity and minimize off-target effects in multiple design, synthesis, and testing cycles. Given the absurdly large number of possible molecules (considering molecules of up to 30 C, N, O, S, or halogen atoms, the synthetically accessible space has been estimated to be > 10 60 molecules!), more automated methods to search the chemical space are highly desirable.