Selective optimization of side activities of drug molecules (the SOSA approach) is an intelligent and potentially more efficient strategy than HTS for the generation of new biological activities. Only a limited number of highly diverse drug molecules are screened, for which bioavailability and toxicity studies have already been performed and efficacy in humans has been confirmed. Once the screening has generated a hit it will be used as the starting point for a drug discovery program. Using traditional medicinal chemistry as well as parallel synthesis, the initial 'side activity' is transformed into the 'main activity' and, conversely, the initial 'main activity' is significantly reduced or abolished. This strategy has a high probability of yielding safe, bioavailable, original and patentable analogues.