Discovery and optimization of pyrazole amides as antagonists of CCR1

Abstract A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds ( S )- 16q and ( S )- 16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties.