Literature DB >> 22197142

Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.

Bruce J Melancon1, Alexander P Lamers, Thomas M Bridges, Gary A Sulikowski, Thomas J Utley, Douglas J Sheffler, Meredith J Noetzel, Ryan D Morrison, J Scott Daniels, Colleen M Niswender, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Michael R Wood.   

Abstract

This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented.
Copyright © 2011 Elsevier Ltd. All rights reserved.

Entities:  

Mesh：

Substances：

Year:  2011        PMID： 22197142      PMCID： PMC3434972          DOI： 10.1016/j.bmcl.2011.11.110

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


  17 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
Journal:  Nat Rev Drug Discov       Date:  2007-09       Impact factor: 84.694

7.  Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia.

Authors:  Anantha Shekhar; William Z Potter; Jeffrey Lightfoot; John Lienemann; Sanjay Dubé; Craig Mallinckrodt; Frank P Bymaster; David L McKinzie; Christian C Felder
Journal:  Am J Psychiatry       Date:  2008-07-01       Impact factor: 18.112

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
View more
  4 in total

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

Authors:  Bruce J Melancon; 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
Journal:  Bioorg Med Chem Lett       Date:  2012-06-15       Impact factor: 2.823

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

Authors:  Agostinho Lemos; Rita Melo; Antonio Jose Preto; Jose Guilherme Almeida; Irina Sousa Moreira; Maria Natalia Dias Soeiro Cordeiro
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.  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
  4 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.