Novel hexahydropyrrolo[3,4-c]pyrrole CCR5 antagonists

Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.

Graphical abstractUtilizing a high-throughput screening lead as a starting point, an information-based approach led to the discovery of a novel series of CCR5 antagonists, exemplified by compound 4. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.Figure optionsDownload full-size imageDownload as PowerPoint slide