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Your search keyword '"Wood, Michael"' showing total 3 results
Start Over Author "Wood, Michael" Topic molecular probes Topic muscarinic receptors Publication Type Academic Journals
3 results on '"Wood, Michael"'

1. Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: The continued optimization of an MLPCN probe molecule

Author

Poslusney, Michael S., Melancon, Bruce J., Gentry, Patrick R., Sheffler, Douglas J., Bridges, Thomas M., Utley, Thomas J., Daniels, J. Scott, Niswender, Colleen M., Conn, P. Jeffrey, Lindsley, Craig W., and Wood, Michael R.

Subjects
*ISATIN, *MUSCARINIC receptors, *MOLECULAR probes, *CYCLIC compounds, *SUBSTITUTION reactions, *KETONES, *STRUCTURE-activity relationships
Abstract

Abstract: 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. [Copyright &y& Elsevier]

Published
2013
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2. Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012

Author

Melancon, Bruce J., Utley, Thomas J., Sevel, Christian, Mattmann, Margrith E., Cheung, Yiu-Yin, Bridges, Thomas M., Morrison, Ryan D., Sheffler, Douglas J., Niswender, Colleen M., Scott Daniels, J., Jeffrey Conn, P., Lindsley, Craig W., and Wood, Michael R.

Subjects
*MOLECULAR probes, *MUSCARINIC receptors, *MUSCARINIC antagonists, *ORGANIC synthesis, *DATA analysis, *AZETIDINE, *TISSUE scaffolds
Abstract

Abstract: This Paper describes the continued optimization of an MLPCN probe molecule M1 antagonist (ML012) through an iterative parallel synthesis approach. After several rounds of modifications of the parent compound, we arrived at a new azetidine scaffold that displayed improved potency while maintaining a desirable level of selectivity over other muscarinic receptor subtypes. Data for representative molecules 7w (VU0452865) and 12a (VU0455691) are presented. [Copyright &y& Elsevier]

Published
2012
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3. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): The development of ML169, an MLPCN probe

Author

Reid, Paul R., Bridges, Thomas M., Sheffler, Douglas J., Cho, Hyekyung P., Lewis, L. Michelle, Days, Emily, Daniels, J. Scott, Jones, Carrie K., Niswender, Colleen M., Weaver, C. David, Conn, P. Jeffrey, Lindsley, Craig W., and Wood, Michael R.

Subjects
*DRUG development, *ALLOSTERIC regulation, *ACETYLCHOLINE, *ALZHEIMER'S disease, *MUSCARINIC receptors, *MOLECULAR probes, *STRUCTURE-activity relationship in pharmacology
Abstract

Abstract: This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M1 PAM with an in vitro profile comparable to the prototypical M1 PAM, BQCA, but with an improved brain to plasma ratio. [Copyright &y& Elsevier]

Published
2011
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