Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries was written by Willems, Sabine;Mueller, Marcel;Ohrndorf, Julia;Heering, Jan;Proschak, Ewgenij;Merk, Daniel. And the article was included in ChemMedChem in 2022.Safety of Quinoxalin-2-amine This article mentions the following:
Several lines of evidence suggest the ligand-sensing transcription factor Nurr1 as a promising target to treat neurodegenerative diseases. Nurr1 modulators to validate and exploit this therapeutic potential are rare, however. To identify novel Nurr1 agonist chemotypes, we have employed the Nurr1 activator amodiaquine as template for microscale analog library synthesis. The first set of analogs was based on the 7-chloroquiolin-4-amine core fragment of amodiaquine and revealed superior N-substituents compared to diethylaminomethylphenol contained in the template. A second library of analogs was subsequently prepared to replace the chloroquinolineamine scaffold. The two sets of analogs enabled a full scaffold hop from amodiaquine to a novel Nurr1 agonist sharing no structural features with the lead but comprising superior potency on Nurr1. Addnl., pharmacophore modeling based on the entire set of active and inactive analogs suggested key features for Nurr1 agonists. In the experiment, the researchers used many compounds, for example, Quinoxalin-2-amine (cas: 5424-05-5Safety of Quinoxalin-2-amine).
Quinoxalin-2-amine (cas: 5424-05-5) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.Safety of Quinoxalin-2-amine
Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider