| Title: | Substituted Benzylspiroindolin-2-one Analogues as Positive Allosteric Modulators of the Muscarinic Acetylcholine Receptor M1 | ||
| Application Number: | WO 2013071201A1 | Publication date: | 16 May 2013 |
| Priority Application: | 61/558,849 | Priority date: | 11 November 2001 |
| Inventors: | Craig W. Lindsley, Jeffrey P. Conn, Michael R. Wood, Corey R. Hopkins, Bruce J. Melancon, Michael S. Poslusney | ||
| Assignee Company: | N/A | ||
| Disease Area: | Cognition | Biological Target: | Muscarinic M1 Receptor |
| Summary: | This patent application describes the synthesis and evaluation of novel benzylspiroindolinones as potential positive allosteric modulators of the muscarinic M1 receptor. These compounds have potential use in the treatment of cognitive disorders such as Alzheimer’s Disease and as adjuncts in the treatment of schizophrenia. Allosteric receptor modulators enhance the affinity of endogenous ligands and can provide symptomatic relief for diseases where the receptor may be involved. Selective enhancement of muscarinic M1 function is hypothesized to be a useful approach for cognitive enhancement. Since design of orthosteric M1 ligands with sufficient receptor selectivity is very difficult, allosteric ligands represent an alternative approach with promise. | ||
| Primary Markush: |  |
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| Notable substructures: |  |
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| Biological Data: | Example B1M1 EC50 1800 nM, Emax 80% | ||
| Example B22 M1 EC50 3200 nM, Emax 86% | |||
| Example B31 M1 EC50 3800 nM, Emax 76% | |||
The authors declare no competing financial interest.