Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The M, mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M-4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (K-B), cooperativity (alpha beta), and direct agonist properties (tau(B)).
Original languageEnglish
Pages (from-to)8196 - 8200
Number of pages5
JournalJournal of Medicinal Chemistry
Volume56
Issue number20
DOIs
Publication statusPublished - 2013

Cite this

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title = "Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor",
abstract = "The M, mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M-4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (K-B), cooperativity (alpha beta), and direct agonist properties (tau(B)).",
author = "Tracey Huynh and Celine Valant and Crosby, {Ian Travers} and Patrick Sexton and Arthur Christopoulos and Benvenuto Capuano",
year = "2013",
doi = "10.1021/jm401032k",
language = "English",
volume = "56",
pages = "8196 -- 8200",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "AMER CHEMICAL SOC",
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Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor. / Huynh, Tracey; Valant, Celine; Crosby, Ian Travers; Sexton, Patrick; Christopoulos, Arthur; Capuano, Benvenuto.

In: Journal of Medicinal Chemistry, Vol. 56, No. 20, 2013, p. 8196 - 8200.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor

AU - Huynh, Tracey

AU - Valant, Celine

AU - Crosby, Ian Travers

AU - Sexton, Patrick

AU - Christopoulos, Arthur

AU - Capuano, Benvenuto

PY - 2013

Y1 - 2013

N2 - The M, mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M-4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (K-B), cooperativity (alpha beta), and direct agonist properties (tau(B)).

AB - The M, mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M-4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (K-B), cooperativity (alpha beta), and direct agonist properties (tau(B)).

UR - http://pubs.acs.org.ezproxy.lib.monash.edu.au/doi/pdf/10.1021/jm401032k

U2 - 10.1021/jm401032k

DO - 10.1021/jm401032k

M3 - Article

VL - 56

SP - 8196

EP - 8200

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 20

ER -