Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule
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This Letter describes the further optimization of an MLPCN probe molecule (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M1 PAMs, are presented. These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype.
|Journal||Bioorganic & Medicinal Chemistry Letters|
|Number of pages||5|
|Publication status||Published - 15 Mar 2013|
Copyright © 2013 Elsevier Ltd. All rights reserved.
- Allosteric Regulation, Animals, Humans, Isatin/analogs & derivatives, Protein Binding, Pyrrolidines/chemical synthesis, Rats, Receptor, Muscarinic M1/antagonists & inhibitors, Spiro Compounds/chemistry, Structure-Activity Relationship