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

Utilizing 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.