Literature DB >> 20004578

Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM.

Thomas M Bridges1, J Phillip Kennedy, Hyekyung P Cho, Micah L Breininger, Patrick R Gentry, Corey R Hopkins, P Jeffrey Conn, Craig W Lindsley.   

Abstract

This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS. Copyright 2009 Elsevier Ltd. All rights reserved.

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Year:  2009        PMID： 20004578      PMCID： PMC3177601          DOI： 10.1016/j.bmcl.2009.11.089

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  25 in total

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Authors:  Thomas M Bridges; Ashley E Brady; J Phillip Kennedy; R Nathan Daniels; Nicole R Miller; Kwango Kim; Micah L Breininger; Patrick R Gentry; John T Brogan; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2008-09-10       Impact factor: 2.823

2.  Identification of a family of muscarinic acetylcholine receptor genes.

Authors:  T I Bonner; N J Buckley; A C Young; M R Brann
Journal:  Science       Date:  1987-07-31       Impact factor: 47.728

3.  A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models.

Authors:  Gene G Kinney; Julie A O'Brien; Wei Lemaire; Maryann Burno; Denise J Bickel; Michelle K Clements; Tsing-Bau Chen; David D Wisnoski; Craig W Lindsley; Philip R Tiller; Sheri Smith; Marlene A Jacobson; Cyrille Sur; Mark E Duggan; Douglas J Pettibone; P Jeffrey Conn; David L Williams
Journal:  J Pharmacol Exp Ther       Date:  2004-12-17       Impact factor: 4.030

4.  Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo.

Authors:  Craig W Lindsley; David D Wisnoski; William H Leister; Julie A O'brien; Wei Lemaire; David L Williams; Maryann Burno; Cyrille Sur; Gene G Kinney; Doug J Pettibone; Philip R Tiller; Sheri Smith; Mark E Duggan; George D Hartman; P Jeffrey Conn; Joel R Huff
Journal:  J Med Chem       Date:  2004-11-18       Impact factor: 7.446

Review 5.  Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development.

Authors:  Jürgen Wess; Richard M Eglen; Dinesh Gautam
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6.  A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning.

Authors:  Jana K Shirey; Ashley E Brady; Paulianda J Jones; Albert A Davis; Thomas M Bridges; J Phillip Kennedy; Satyawan B Jadhav; Usha N Menon; Zixiu Xiang; Mona L Watson; Edward P Christian; James J Doherty; Michael C Quirk; Dean H Snyder; James J Lah; Allan I Levey; Michelle M Nicolle; Craig W Lindsley; P Jeffrey Conn
Journal:  J Neurosci       Date:  2009-11-11       Impact factor: 6.167

7.  Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation.

Authors:  Lei Ma; Matthew A Seager; Matthew Seager; Marion Wittmann; Marlene Jacobson; Denise Bickel; Maryann Burno; Keith Jones; Valerie Kuzmick Graufelds; Guangping Xu; Michelle Pearson; Alexander McCampbell; Renee Gaspar; Paul Shughrue; Andrew Danziger; Christopher Regan; Rose Flick; Danette Pascarella; Susan Garson; Scott Doran; Constantine Kreatsoulas; Lone Veng; Craig W Lindsley; William Shipe; Scott Kuduk; Cyrille Sur; Gene Kinney; Guy R Seabrook; William J Ray
Journal:  Proc Natl Acad Sci U S A       Date:  2009-08-26       Impact factor: 11.205

Review 8.  Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders.

Authors:  P Jeffrey Conn; Carrie K Jones; Craig W Lindsley
Journal:  Trends Pharmacol Sci       Date:  2009-02-07       Impact factor: 14.819

Review 9.  Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders.

Authors:  P Jeffrey Conn; Arthur Christopoulos; Craig W Lindsley
Journal:  Nat Rev Drug Discov       Date:  2009-01       Impact factor: 84.694

Review 10.  Muscarinic acetylcholine receptors as CNS drug targets.

Authors:  Christopher J Langmead; Jeannette Watson; Charlie Reavill
Journal:  Pharmacol Ther       Date:  2007-12-20       Impact factor: 12.310
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  27 in total

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Journal:  J Med Chem       Date:  2012-01-06       Impact factor: 7.446

Review 2.  The antipsychotic potential of muscarinic allosteric modulation.

Authors:  Thomas M Bridges; Evan P LeBois; Corey R Hopkins; Michael R Wood; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley
Journal:  Drug News Perspect       Date:  2010-05

Review 3.  Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.

Authors:  Craig W Lindsley; Kyle A Emmitte; Corey R Hopkins; Thomas M Bridges; Karen J Gregory; Colleen M Niswender; P Jeffrey Conn
Journal:  Chem Rev       Date:  2016-02-16       Impact factor: 60.622

Review 4.  Emerging paradigms in GPCR allostery: implications for drug discovery.

Authors:  Denise Wootten; Arthur Christopoulos; Patrick M Sexton
Journal:  Nat Rev Drug Discov       Date:  2013-08       Impact factor: 84.694

Review 5.  Cholinergic interneurons in the dorsal and ventral striatum: anatomical and functional considerations in normal and diseased conditions.

Authors:  Kalynda K Gonzales; Yoland Smith
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6.  Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

Authors:  Changho Han; Arindam Chatterjee; Meredith J Noetzel; Joseph D Panarese; Emery Smith; Peter Chase; Peter Hodder; Colleen Niswender; P Jeffrey Conn; Craig W Lindsley; Shaun R Stauffer
Journal:  Bioorg Med Chem Lett       Date:  2014-11-18       Impact factor: 2.823

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

Authors:  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
Journal:  Bioorg Med Chem Lett       Date:  2012-12-01       Impact factor: 2.823

Review 8.  Emerging approaches for treatment of schizophrenia: modulation of cholinergic signaling.

Authors:  Daniel J Foster; Carrie K Jones; P Jeffrey Conn
Journal:  Discov Med       Date:  2012-12       Impact factor: 2.970

Review 9.  Development of M1 mAChR allosteric and bitopic ligands: prospective therapeutics for the treatment of cognitive deficits.

Authors:  Briana J Davie; Arthur Christopoulos; Peter J Scammells
Journal:  ACS Chem Neurosci       Date:  2013-05-23       Impact factor: 4.418

10.  Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease.

Authors:  Ditte Dencker; Morgane Thomsen; Gitta Wörtwein; Pia Weikop; Yinghong Cui; Jongrye Jeon; Jürgen Wess; Anders Fink-Jensen
Journal:  ACS Chem Neurosci       Date:  2012       Impact factor: 4.418
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