In modern drug discovery, high-throughput screening may generate promising lead compounds that are less than ideal with respect to important parameters such as absorption, distribution, metabolism, and excretion (ADME). In the process of lead optimization, various structural features are fine-tuned and physicochemical properties such as the basicity (pKa [1]), lipophilicity (logD), solubility (Solint), and clearance rates (CLint) are improved.[2] ...