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Literature DB >> 24485781

Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M(1) positive allosteric modulators.

Scott D Kuduk¹, Christina N Di Marco², Jonathan R Saffold², William J Ray³, Lei Ma³, Marion Wittmann³, Kenneth A Koeplinger⁴, Charles D Thompson⁴, George D Hartman², Mark T Bilodeau², Douglas C Beshore².

Abstract

A series of methoxynaphthalene amides were prepared and evaluated as alternatives to quinolizidinone amide M1 positive allosteric modulators. A methoxy group was optimal for M1 activity and addressed key P-gp issues present in the aforementioned quinolizidinone amide series.

Entities: Chemical Gene

Keywords: Allosteric modulator; Alzheimer’s disease; M(1); Muscarinic; P-glycoprotein

Mesh：

Substances：

Year: 2014 PMID： 24485781 DOI： 10.1016/j.bmcl.2014.01.012

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

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Cited

6 in total

1. 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

2. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

Authors: Joseph D Panarese; Hykeyung P Cho; Jeffrey J Adams; Kellie D Nance; Pedro M Garcia-Barrantes; Sichen Chang; Ryan D Morrison; Anna L Blobaum; Colleen M Niswender; Shaun R Stauffer; P Jeffrey Conn; Craig W Lindsley
Journal: Bioorg Med Chem Lett Date: 2016-04-29 Impact factor: 2.823

Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M(1) positive allosteric modulators.

1. 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.

2. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

3. Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor.

Review 4. Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.

5. The Role of Orthosteric Building Blocks of Bitopic Ligands for Muscarinic M1 Receptors.

Review 6. Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.