title: Quinoxalines as potent selective CRFRs ligands for monitoring and brain diagnostic.
abstract: The paper highlighted quinoxalines as potent ligands to corticotropin-releasing factor receptor types 1 and 2. The content includes design and structure-activity relationship of 50 model substances to CRFR1, CRFR2α and CRF2β, respectively. It is important to bear in mind, that our concept has based on challenging research task, designing for selective CRFRs ligands. Because,: (i) These macromolecules can bond more than one ligand, thus causing for a distinct physiological response; (ii) CRFRs also participate readily in protein-protein interactions; (iii) CRFRs have two step activation mechanism and; (iv) CRFR1 has low selectivity. In spite of, numerous research efforts, which have been devoted to the isolation of series peptidic and non-peptidic CRFRs agonists, the poor penetration across blood-brain barrier restricts, their wide application in the clinical practice. Furthermore, the biological role of CRFR2 is not yet fully understood. For that reason, the studies of the structure-activity relationship have significant impact in the field. The great advantages of quinoxalines as prospective ligands are based on their: (a) One-step synthetic road, using mild experimental conditions and, allowing to involve various functional groups in the molecular scaffold as well as good-to-excellent yields, employing Fischer and Hinsberg methods; (b) High selectivity to CRFRs sub-types and; (c) Tunable fluorescence emission within the frame of a large scale of the electromagnetic spectrum ∈ 500-700 nm.
authors.affiliation: Lehrstuhl für Analytische Chemie, Institut für Umweltforschung, Fakultät für Chemie, Universität Dortmund, Otto-Hahn-Straße 6, 44227 Dortmund, Nordrhein-Westfalen, Germany. Electronic address: B.Ivanova@infu.uni-dortmund.de.
authors.forename: Bojidarka
authors.initials: B
authors.lastname: Ivanova
authors.affiliation: Lehrstuhl für Analytische Chemie, Institut für Umweltforschung, Fakultät für Chemie, Universität Dortmund, Otto-Hahn-Straße 6, 44227 Dortmund, Nordrhein-Westfalen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Spiteller
mesh_terms: D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D006860:Hydrogen Bonding; D008024:Ligands; D066244:Proton Magnetic Resonance Spectroscopy; D011810:Quinoxalines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011810:Quinoxalines; D018019:Receptors, Corticotropin-Releasing Hormone
keywords: Brain diagnostic; CRFRs; Quinoxalines