>

Discovery of a potent M antagonist with improved clearance profile. Part 2: Pyrrolidine amide-based antagonists

Authors

Orsi DL Douglas L , Felts AS Andrew S , Rodriguez AL Alice L , Vinson PN Paige N , Cho HP Hyekyung P , Chang S Sichen , Blobaum AL Anna L , Niswender CM Colleen M , Conn PJ P Jeffrey , Jones CK Carrie K , Lindsley CW Craig W , Han C Changho .
Bioorganic & medicinal chemistry letters. 2022 10 10; 78().
129021

Abstract

This Letter describes our ongoing effort to improve the clearance of selective M antagonists. Herein, we report the replacement of the previously disclosed piperidine amide (4, disclosed in Part 1) with a pyrrolidine amide core. Several compounds within this series provided good potency, subtype selectivity, and low to moderate clearance profiles. Interestingly, the left-hand side SAR for this series diverged from our earlier efforts.