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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	23
Udgave nummer	2
Sider (fra-til)	412-6
Antal sider	5
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2012.11.092
Status	Udgivet - 15 jan. 2013
Udgivet eksternt	Ja

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10.1016/j.bmcl.2012.11.092

Citationsformater

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

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, bind 23, nr. 2, s. 412-6. https://doi.org/10.1016/j.bmcl.2012.11.092

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

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.",

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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year = "2013",

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day = "15",

doi = "10.1016/j.bmcl.2012.11.092",

language = "English",

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T1 - Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137

T2 - continued optimization of an MLPCN probe molecule

AU - Melancon, Bruce J

AU - Poslusney, Michael S

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

PY - 2013/1/15

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N2 - 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.

AB - 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.

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

U2 - 10.1016/j.bmcl.2012.11.092

DO - 10.1016/j.bmcl.2012.11.092

M3 - Journal article

C2 - 23237839

SN - 0960-894X

VL - 23

SP - 412

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

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