There be Rings in them Drugs
This month, we choose to highlight a paper published by researchers at UCB in which cheminformatics techniques were utilised to provide a detailed analysis of the ring systems present in drug and clinical trial compounds. Using a virtual fragmentation technique on drug and clinical trial compound libraries, the authors catalogued the ring systems present, which allowed them to compare the chemical space explored. 378 ring systems were found in drugs, while 450 were found in clinical trials, with 70% of clinical trial compounds containing only ring systems previously found in drugs – this reflects the nature of drug discovery where fast follow projects use previously defined knowledge to design new compounds. The authors collated a library of over 450,000 ring systems that have been synthesised and reported on. Interestingly, the researchers found that many of the new ring systems coming through in clinical trials are only 1 or 2 atom changes away from the ring systems found in previous drugs, again reflecting the step change nature of medicinal chemistry, and they use this to enumerate a virtual library of 4000 predicted future clinical trial rings systems. Reducing the 450,000 possible rings to 4000 that are likely to make it to clinical trial provides a curated pool for medicinal chemists to explore in their projects at UCB.
Reading this paper, we wonder if a more time-dependent analysis of ring systems that pass clinical trials and make it into market, as well as those that have failed in clinical trials, would yield a more refined analysis. The authors note in their conclusion that an analysis of the failed compounds at the different stages of clinical trials was difficult because of the lack of data showing why compounds are not passed through to the next phase. As ever, better reporting of failures would increase the quality of data available to cheminformaticians for analyses such as these.
Shearer, et. al. Rings in Clinical Trials and Drugs: Present and Future.