Literature DB >> 22749871

Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012.

Bruce J Melancon1, Thomas J Utley, Christian Sevel, Margrith E Mattmann, Yiu-Yin Cheung, Thomas M Bridges, Ryan D Morrison, Douglas J Sheffler, Colleen M Niswender, J Scott Daniels, P Jeffrey Conn, Craig W Lindsley, Michael R Wood.   

Abstract

This Paper describes the continued optimization of an MLPCN probe molecule M(1) antagonist (ML012) through an iterative parallel synthesis approach. After several rounds of modifications of the parent compound, we arrived at a new azetidine scaffold that displayed improved potency while maintaining a desirable level of selectivity over other muscarinic receptor subtypes. Data for representative molecules 7w (VU0452865) and 12a (VU0455691) are presented.
Copyright © 2012 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 22749871      PMCID： PMC3883446          DOI： 10.1016/j.bmcl.2012.06.018

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


  19 in total

1.  Pharmacological comparison of muscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists.

Authors:  Julia N Heinrich; John A Butera; Tikva Carrick; Angela Kramer; Dianne Kowal; Tim Lock; Karen L Marquis; Mark H Pausch; Mike Popiolek; Shaiu-Ching Sun; Eugene Tseng; Albert J Uveges; Scott C Mayer
Journal:  Eur J Pharmacol       Date:  2009-01-11       Impact factor: 4.432

Review 2.  Molecular biology of muscarinic acetylcholine receptors.

Authors:  J Wess
Journal:  Crit Rev Neurobiol       Date:  1996

3.  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

4.  Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric muscarinic receptor modulators.

Authors:  Scott D Kuduk; Ronald K Chang; Christina N Di Marco; William J Ray; Lei Ma; Marion Wittmann; Matthew A Seager; Kenneth A Koeplinger; Charles D Thompson; George D Hartman; Mark T Bilodeau
Journal:  ACS Med Chem Lett       Date:  2010-06-04       Impact factor: 4.345

5.  Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM.

Authors:  Thomas M Bridges; J Phillip Kennedy; Meredith J Noetzel; Micah L Breininger; Patrick R Gentry; P Jeffrey Conn; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2010-02-01       Impact factor: 2.823

Review 6.  Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development.

Authors:  Jürgen Wess; Richard M Eglen; Dinesh Gautam
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Authors:  Anantha Shekhar; William Z Potter; Jeffrey Lightfoot; John Lienemann; Sanjay Dubé; Craig Mallinckrodt; Frank P Bymaster; David L McKinzie; Christian C Felder
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Review 8.  Fragile X syndrome: an update on developing treatment modalities.

Authors:  Aileen Healy; Roger Rush; Timothy Ocain
Journal:  ACS Chem Neurosci       Date:  2011-03-22       Impact factor: 4.418

Review 9.  Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications.

Authors:  Jürgen Wess
Journal:  Annu Rev Pharmacol Toxicol       Date:  2004       Impact factor: 13.820

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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  6 in total

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2.  In Silico Studies Targeting G-protein Coupled Receptors for Drug Research Against Parkinson's Disease.

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Journal:  Curr Neuropharmacol       Date:  2018       Impact factor: 7.363

3.  Synthesis and biological characterization of a series of novel diaryl amide M₁ antagonists.

Authors:  Michael S Poslusney; Christian Sevel; Thomas J Utley; Thomas M Bridges; Ryan D Morrison; Nathan R Kett; Douglas J Sheffler; Colleen M Niswender; J S Daniels; P J Conn; Craig W Lindsley; Michael R Wood
Journal:  Bioorg Med Chem Lett       Date:  2012-09-23       Impact factor: 2.823

4.  Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.

Authors:  Jason T Manka; Alice L Rodriguez; Ryan D Morrison; Daryl F Venable; Hyekyung P Cho; Anna L Blobaum; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2013-07-23       Impact factor: 2.823

5.  Discovery of PIPE-359, a Brain-Penetrant, Selective M1 Receptor Antagonist with Robust Efficacy in Murine MOG-EAE.

Authors:  Thomas O Schrader; Yifeng Xiong; Ariana O Lorenzana; Alexander Broadhead; Karin J Stebbins; Michael M Poon; Christopher Baccei; Daniel S Lorrain
Journal:  ACS Med Chem Lett       Date:  2020-12-24       Impact factor: 4.345

6.  Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models.

Authors:  Catherine H Choi; Brian P Schoenfeld; Aaron J Bell; Joseph Hinchey; Cory Rosenfelt; Michael J Gertner; Sean R Campbell; Danielle Emerson; Paul Hinchey; Maria Kollaros; Neal J Ferrick; Daniel B Chambers; Steven Langer; Steven Sust; Aatika Malik; Allison M Terlizzi; David A Liebelt; David Ferreiro; Ali Sharma; Eric Koenigsberg; Richard J Choi; Natalia Louneva; Steven E Arnold; Robert E Featherstone; Steven J Siegel; R Suzanne Zukin; Thomas V McDonald; Francois V Bolduc; Thomas A Jongens; Sean M J McBride
Journal:  Front Behav Neurosci       Date:  2016-06-30       Impact factor: 3.558
  6 in total

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