Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004

Tracey Huynh; Celine Valant; Ian Travers Crosby; Patrick Sexton; Arthur Christopoulos; Benvenuto Capuano

doi:10.1021/acschemneuro.5b00035

Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004

Tracey Huynh, Celine Valant, Ian Travers Crosby, Patrick Sexton, Arthur Christopoulos, Benvenuto Capuano

Research output: Contribution to journal › Article › Research › peer-review

11 Citations (Scopus)

Abstract

The M4 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 M4 PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (a?), and direct agonist properties (B).

Original language	English
Pages (from-to)	838 - 844
Number of pages	7
Journal	ACS Chemical Neuroscience
Volume	6
Issue number	6
DOIs	https://doi.org/10.1021/acschemneuro.5b00035
Publication status	Published - 2015

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10.1021/acschemneuro.5b00035

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title = "Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004",

abstract = "The M4 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 M4 PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (a?), and direct agonist properties (B).",

author = "Tracey Huynh and Celine Valant and Crosby, {Ian Travers} and Patrick Sexton and Arthur Christopoulos and Benvenuto Capuano",

year = "2015",

doi = "10.1021/acschemneuro.5b00035",

language = "English",

volume = "6",

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journal = "ACS Chemical Neuroscience",

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T1 - Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004

AU - Huynh, Tracey

AU - Valant, Celine

AU - Crosby, Ian Travers

AU - Sexton, Patrick

AU - Christopoulos, Arthur

AU - Capuano, Benvenuto

PY - 2015

Y1 - 2015

N2 - The M4 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 M4 PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (a?), and direct agonist properties (B).

AB - The M4 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 M4 PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (a?), and direct agonist properties (B).

UR - http://pubs.acs.org/doi/pdf/10.1021/acschemneuro.5b00035

U2 - 10.1021/acschemneuro.5b00035

DO - 10.1021/acschemneuro.5b00035

M3 - Article

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VL - 6

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EP - 844

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

IS - 6

ER -

Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004

Abstract

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The Janus face of G Protein-Coupled Receptors: Implications for Disease Mechanisms and Opportunities for Drug Discovery

NHMRC Principal Research Fellow

NHMRC Research Fellowship

Cite this

Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004

Abstract

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The Janus face of G Protein-Coupled Receptors: Implications for Disease Mechanisms and Opportunities for Drug Discovery

NHMRC Principal Research Fellow

NHMRC Research Fellowship

Cite this