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

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Pages (from-to)838 - 844
Number of pages7
JournalACS Chemical Neuroscience
Volume6
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

@article{a94afa472adb415f98663d80c43bf74c,
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",
pages = "838 -- 844",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "6",

}

Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004. / Huynh, Tracey; Valant, Celine; Crosby, Ian Travers; Sexton, Patrick; Christopoulos, Arthur; Capuano, Benvenuto.

In: ACS Chemical Neuroscience, Vol. 6, No. 6, 2015, p. 838 - 844.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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

VL - 6

SP - 838

EP - 844

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 6

ER -