R-group replacement database for medicinal chemistry

AIM: Generation of an R-group replacement system for compound optimization in medicinal chemistry. MATERIALS & METHODS: From bioactive compounds, analogue series (ASs) were systematically extracted and from these ASs, all R-groups were isolated and further analyzed. EXEMPLARY RESULTS & DATA: From more than 17,000 ASs, more than 50,000 unique R-groups were isolated. For the 500 most frequently used R-groups, preferred replacements were identified and organized in hierarchies. All original data and an R-group replacement database are made available in an open access deposition. LIMITATIONS & NEXT STEPS: The searchable database has no limitations and can easily be modified using the source data we provide. The next step will be applying this R-group resource in practical medicinal chemistry projects as decision support.