selective factor XIa serine protease inhibitor
oral in higher species, eff. in thrombosis model
from PK optimization of prior series
J. Med. Chem., May 26, 2020
Bristol Myers Squibb, Princeton, NJ
“Compound 6f” is a potent macrocyclic factor XIa inhibitor (<1 nM) that is highly selective against other serine proteases and has excellent oral PK (high bioavailability, low clearance). The BMS team was able to troubleshoot metabolic instability through met. ID, which revealed a hotspot outside of the macrocycle.