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Discovery of a potent M 5 antagonist with improved clearance profile. Part 2: Pyrrolidine amide-based antagonists.

Authors :
Orsi DL
Felts AS
Rodriguez AL
Vinson PN
Cho HP
Chang S
Blobaum AL
Niswender CM
Conn PJ
Jones CK
Lindsley CW
Han C
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2022 Dec 15; Vol. 78, pp. 129021. Date of Electronic Publication: 2022 Oct 10.
Publication Year :
2022

Abstract

This Letter describes our ongoing effort to improve the clearance of selective M <subscript>5</subscript> 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.<br />Competing Interests: Declaration of Competing Interest Some authors are inventors on application for composition of matter patents that protect several series of M(5) antagonists.<br /> (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
78
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
36228968
Full Text :
https://doi.org/10.1016/j.bmcl.2022.129021