Quinoxalines as potent selective CRFRs ligands for monitoring and brain diagnostic

• Quinoxalines are prospective class of selective ligands to CRFR1, CRFR2α and CRF2β.
• They can be used for fluorescence imaging, due to their emission ∈∈ 500–700 nm.
• Quinoxalines can be prominent ligands for monitoring of mental disorders.
• “Free energy” is a powerful quantitative criterion for the binding affinity.

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.

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