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Literature DB >> 23062550

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

Michael S Poslusney¹, 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.

Abstract

Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement experiments demonstrated the competitive, orthosteric binding of these compounds; human selectivity data are presented.

Entities: Chemical Disease Gene Species

Mesh：

Substances：

Year: 2012 PMID： 23062550 PMCID： PMC3897205 DOI： 10.1016/j.bmcl.2012.09.011

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

15 in total

1. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.

Authors: Alice L Rodriguez; Mark D Grier; Carrie K Jones; Elizabeth J Herman; Alexander S Kane; Randy L Smith; Richard Williams; Ya Zhou; Joy E Marlo; Emily L Days; Tasha N Blatt; Satyawan Jadhav; Usha N Menon; Paige N Vinson; Jerri M Rook; Shaun R Stauffer; Colleen M Niswender; Craig W Lindsley; C David Weaver; P Jeffrey Conn
Journal: Mol Pharmacol Date: 2010-10-05 Impact factor: 4.436

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

3. A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning.

Authors: Douglas J Sheffler; Richard Williams; Thomas M Bridges; Zixiu Xiang; Alexander S Kane; Nellie E Byun; Satyawan Jadhav; Mathew M Mock; Fang Zheng; L Michelle Lewis; Carrie K Jones; Colleen M Niswender; Charles D Weaver; Craig W Lindsley; P Jeffrey Conn
Journal: Mol Pharmacol Date: 2009-04-30 Impact factor: 4.436

4. 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

5. 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

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

Authors: Bruce J Melancon; 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
Journal: Bioorg Med Chem Lett Date: 2011-12-06 Impact factor: 2.823

7. Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4.

Authors: Colleen M Niswender; Kari A Johnson; C David Weaver; Carrie K Jones; Zixiu Xiang; Qingwei Luo; Alice L Rodriguez; Joy E Marlo; Tomas de Paulis; Analisa D Thompson; Emily L Days; Tasha Nalywajko; Cheryl A Austin; Michael Baxter Williams; Jennifer E Ayala; Richard Williams; Craig W Lindsley; P Jeffrey Conn
Journal: Mol Pharmacol Date: 2008-07-29 Impact factor: 4.436

2. Metal-free direct alkylation of unfunctionalized allylic/benzylic sp³ C-H bonds via photoredox induced radical cation deprotonation.

Authors: Rong Zhou; Haiwang Liu; Hairong Tao; Xingjian Yu; Jie Wu
Journal: Chem Sci Date: 2017-04-28 Impact factor: 9.825

2 in total

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

1. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity.

Review 2. The antipsychotic potential of muscarinic allosteric modulation.

3. A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning.

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

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

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

7. Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4.

8. Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.

9. Covalent binding and tissue distribution/retention assessment of drugs associated with idiosyncratic drug toxicity.

Review 10. Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications.

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

2. Metal-free direct alkylation of unfunctionalized allylic/benzylic sp³ C-H bonds via photoredox induced radical cation deprotonation.