Worldwide, contamination of aquatic systems with micro-pollutants, including pharmaceuticals, is one of the challenges for sustainable management of water resources. Although micro-pollutants are present at low concentrations, many of them raise considerable toxicological concerns, particularly when present as components of complex mixtures. Recent research has shown that this problem cannot be sustainably solved with advanced effluent treatment. Therefore, an alternative that might overcome these environmental problems is the design of new pharmaceutical molecules or the re-design of existing pharmaceutical molecules that present the functionality needed for their application and have improved environmental biodegradability. Such re-designing can be performed by small molecular changes in the drug molecule with intact drug moiety which could incorporate the additional attribute such as biodegradability while retaining its pharmacological potency. This proof of concept study provides an approach for the rational re-design of a given pharmaceutical (Propranolol as an example). New derivatives with small molecular changes as compared to propranolol molecule were generated by a non-targeted photolysis process. Generated derivatives with intact drug moieties (an aromatic ring and a β-ethanolamine moiety) were further screened for aerobic biodegradability and pharmacological potency. The feasibility of the approach of re-designing an existing pharmaceutical through non-targeted generation of new derivatives with intact drug moiety and through subsequent screening was demonstrated in this study. Application of such approaches in turn might contribute to the protection of water resources in a truly sustainable manner.