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Sulikowski Lab

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

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.