Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.
AUTHORS
Melancon
BJBruce J ,
Lamers
AP Alexander P ,
Bridges
TM Thomas M ,
Sulikowski
GA Gary A ,
Utley
TJ Thomas J ,
Sheffler
DJ Douglas J ,
Noetzel
MJ Meredith J ,
Morrison
RD Ryan D ,
Daniels
JS J Scott ,
Niswender
CM Colleen M ,
Jones
CK Carrie K ,
Conn
PJ P Jeffrey ,
Lindsley
CW Craig W ,
Wood
MR Michael R .
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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