molecules of the month

The BMS CCR2 inhibitor, BMS-753426, is a potent, oral follow-up molecule to prior clinical candidate, BMS-741672. A small change from a methyl and isopropyl-substituted tertiary amine to a t-butyl secondary amine led to a significant improvement in PK properties including lower clearance and higher bioavailability across species, including cyno. The compound has four nitrogen-bearing stereocenters but >100 g were prepared without a single column chromatography purification. The authors suggest that dual CCR2 and CCR5 inhibition may be more successful in various indications, and the related molecule BMS-813160 is a dual antagonist in several clinical trials.