Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.
AUTHORS
Melancon
BJ ,
Lamers
AP ,
Bridges
TM ,
Sulikowski
GA ,
Utley
TJ ,
Sheffler
DJ ,
Noetzel
MJ ,
Morrison
RD ,
Daniels
JS ,
Niswender
CM ,
Jones
CK ,
Conn
PJ ,
Lindsley
CW ,
Wood
MR ,
. Bioorganic & medicinal chemistry letters. 2012 1 15; 22(2). 1044-8
- PMID: 22197142 [PubMed].
- PMCID: PMC3434972.
- NIHMSID: NIHMS346753
ABSTRACT
This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented.
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Tags: 2012