Development of Fluorinated Non-Peptidic Ghrelin Receptor Ligands for Potential Use in Molecular Imaging

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Apr 6

PMID 28379199

Citations 4

Authors

Rares-Petru Moldovan

Sylvia Els-Heindl

Dennis J Worm

Torsten Kniess

Michael Kluge

Annette G Beck-Sickinger

Winnie Deuther-Conrad

Ute Krugel

Peter Brust

Affiliations

Soon will be listed here.

Abstract

The ghrelin receptor (GhrR) is a widely investigated target in several diseases. However, the current knowledge of its role and distribution in the brain is limited. Recently, the small and non-peptidic compound ()-6-(4-bromo-2-fluorophenoxy)-3-((1-isopropylpiperidin-3-yl)methyl)-2-methylpyrido[3,2-d]pyrimidin-4(3)-one (()-) has been described as a GhrR ligand with high binding affinity. Here, we describe the synthesis of fluorinated derivatives, the in vitro evaluation of their potency as partial agonists and selectivity at GhrRs, and their physicochemical properties. These results identified compounds ()-, ()-, and ()- as suitable parent molecules for F-labeled positron emission tomography (PET) radiotracers to enable future investigation of GhrR in the brain.

Citing Articles

Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.

Giorgioni G, Del Bello F, Quaglia W, Botticelli L, Cifani C, Micioni Di Bonaventura E J Med Chem. 2022; 65(4):3098-3118.

PMID: 35157454 PMC: 8883476. DOI: 10.1021/acs.jmedchem.1c02191.

Development of a ghrelin receptor inverse agonist for positron emission tomography.

Bergmann R, Chollet C, Els-Heindl S, Ullrich M, Berndt N, Pietzsch J Oncotarget. 2021; 12(5):450-474.

PMID: 33747360 PMC: 7939532. DOI: 10.18632/oncotarget.27895.

A Decade's Progress in the Development of Molecular Imaging Agents Targeting the Growth Hormone Secretagogue Receptor.

Childs M, Luyt L Mol Imaging. 2020; 19:1536012120952623.

PMID: 33104445 PMC: 8865914. DOI: 10.1177/1536012120952623.

Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor.

Abbas A, Yu L, Lalonde T, Wu D, Thiessen J, Luyt L Mol Imaging. 2018; 17:1536012118809587.

PMID: 30394854 PMC: 6236854. DOI: 10.1177/1536012118809587.

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