AI Article Synopsis
- * Researchers improved Ro 13-3978 by replacing the aryl trifluoromethyl group with a difluoroethyl group to eliminate antiandrogenic effects and substituting hydrogen with deuterium in the dimethyl substructure for better metabolic stability.
- * These modifications resulted in the development of AR102, a promising drug candidate effective against schistosomes, with favorable pharmacokinetic properties and safety.
Article Abstract
Aryl hydantoins were identified in the early 1980s as a promising antischistosomal chemotype. However, as exemplified by Ro 13-3978, this compound series produced antiandrogenic side effects on the host, a not unexpected outcome given their structural similarity to the antiandrogenic drug nilutamide. The two key advances in our optimization of Ro 13-3978 were swapping the aryl trifluoromethyl substituent with a difluoroethyl to abolish antiandrogenic effects and replacing the hydrogen atoms of the -dimethyl substructure with deuterium atoms to increase metabolic stability. Combining these two structural changes led to the discovery of single-dose drug candidate AR102, a compound with potent, selective, and broad-spectrum activity against schistosomes, a long pharmacokinetic half-life in preclinical species, and an acceptable safety profile.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acsinfecdis.4c00677 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!