- MK-7622: A First-in-Class M1 Positive Allosteric Modulator Development Candidate
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Identification of ligands that selectively activate the M1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.
- Beshore, Douglas C.,Di Marco, Christina N.,Chang, Ronald K.,Greshock, Thomas J.,Ma, Lei,Wittmann, Marion,Seager, Matthew A.,Koeplinger, Kenneth A.,Thompson, Charles D.,Fuerst, Joy,Hartman, George D.,Bilodeau, Mark T.,Ray, William J.,Kuduk, Scott D.
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supporting information
p. 652 - 656
(2018/05/14)
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- PROCESS FOR MAKING M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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This invention provides novel processes for the preparation of compounds such as 3-[(1S,2S)-2-hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]-quinazolin-4(3H)-one, salts and derivatives thereof. The compounds synthesized by the processes of the invention are useful for treating Alzheimer's disease and other diseases (e.g., cognitive impairment, schizophrenia, pain disorders, and sleep disorders) mediated by the muscarinic M1 receptor.
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- DIHYDROBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to dihydrobenzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease
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Page/Page column 33
(2012/04/23)
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- PYRANYL ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to pyranyl aryl methyl benzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as ALzheimer?s disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor
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Page/Page column 41-42
(2011/04/14)
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- AMINOBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to aminobenzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor
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Page/Page column 38
(2011/08/03)
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- ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to benzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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Page/Page column 38-39
(2010/07/10)
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