Synthesis of Novel Benzo[b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors
Л. Н. Куликова, Ghulam Reza Raesi, D.D. Levickaya, Rosa Purgatorio, Gabriella La Spada, Marco Catto, Cosimo Altomare, Leonid G. Voskressensky
Abstract
In this work, 2-alkyl-10-chloro-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines were obtained and their reactivity was studied. Novel derivatives of the tricyclic scaffold, including 1-phenylethynyl (5), 1-indol-3-yl (8), and azocino[4,5-b]quinoline (10) derivatives, were synthesized and characterized herein for the first time. Among the newly synthesized derivatives, 5c–h proved to be MAO B inhibitors with potency in the low micromolar range. In particular, the 1-(2-(4-fluorophenyl)ethynyl) analog 5g achieved an IC50 of 1.35 μM, a value close to that of the well-known MAO B inhibitor pargyline.
Topics & Concepts
ChemistryQuinolinePargylinePotencyStereochemistryTricyclicReactivity (psychology)IC50AlkylCombinatorial chemistryMedicinal chemistryIn vitroEnzymeMonoamine oxidaseOrganic chemistryBiochemistryAlternative medicineMedicinePathologySynthesis and Biological EvaluationSynthesis and pharmacology of benzodiazepine derivativesPhenothiazines and Benzothiazines Synthesis and Activities