Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule

Bruce J Melancon; Michael S Poslusney; Patrick R Gentry; James C Tarr; Douglas J Sheffler; Margrith E Mattmann; Thomas M Bridges; Thomas J Utley; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Michael R Wood

doi:10.1016/j.bmcl.2012.11.092

Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule

Bruce J Melancon, Michael S Poslusney, Patrick R Gentry, James C Tarr, Douglas J Sheffler, Margrith E Mattmann, Thomas M Bridges, Thomas J Utley, J Scott Daniels, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley, Michael R Wood

19 Citations (Scopus)

Abstract

This Letter describes the continued optimization of an MLPCN probe molecule (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M(1) PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M(1) receptor was also maintained.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	23
Issue number	2
Pages (from-to)	412-6
Number of pages	5
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.092
Publication status	Published - 15 Jan 2013
Externally published	Yes

Keywords

Inhibitory Concentration 50
Isatin/analogs & derivatives
Molecular Probes/chemistry
Molecular Structure
Monoamine Oxidase Inhibitors/pharmacology
Receptor, Muscarinic M1/drug effects

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10.1016/j.bmcl.2012.11.092

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Melancon, B. J., Poslusney, M. S., Gentry, P. R., Tarr, J. C., Sheffler, D. J., Mattmann, M. E., Bridges, T. M., Utley, T. J., Daniels, J. S., Niswender, C. M., Conn, P. J., Lindsley, C. W., & Wood, M. R. (2013). Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule. Bioorganic & Medicinal Chemistry Letters, 23(2), 412-6. https://doi.org/10.1016/j.bmcl.2012.11.092

Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137 : continued optimization of an MLPCN probe molecule. / Melancon, Bruce J; Poslusney, Michael S; Gentry, Patrick R et al.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 23, No. 2, 15.01.2013, p. 412-6.

Research output: Contribution to journal › Journal article › Research › peer-review

Melancon, BJ, Poslusney, MS, Gentry, PR, Tarr, JC, Sheffler, DJ, Mattmann, ME, Bridges, TM, Utley, TJ, Daniels, JS, Niswender, CM, Conn, PJ, Lindsley, CW & Wood, MR 2013, 'Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule', Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 2, pp. 412-6. https://doi.org/10.1016/j.bmcl.2012.11.092

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abstract = "This Letter describes the continued optimization of an MLPCN probe molecule (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M(1) PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M(1) receptor was also maintained.",

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AU - Melancon, Bruce J

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AU - Gentry, Patrick R

AU - Tarr, James C

AU - Sheffler, Douglas J

AU - Mattmann, Margrith E

AU - Bridges, Thomas M

AU - Utley, Thomas J

AU - Daniels, J Scott

AU - Niswender, Colleen M

AU - Conn, P Jeffrey

AU - Lindsley, Craig W

AU - Wood, Michael R

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KW - Inhibitory Concentration 50

KW - Isatin/analogs & derivatives

KW - Molecular Probes/chemistry

KW - Molecular Structure

KW - Monoamine Oxidase Inhibitors/pharmacology

KW - Receptor, Muscarinic M1/drug effects

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DO - 10.1016/j.bmcl.2012.11.092

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EP - 416

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 2

ER -

Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule

Abstract

Keywords

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