6533b835fe1ef96bd129f748

RESEARCH PRODUCT

Synthesis of new melatoninergic hexahydroindenopyridines

Inmaculada BerenguerDaniel-henri CaignardLaura MorenoAmelia DíazJavier PárragaDiego CortesNuria CabedoBruno FigadèrePaloma Marín

subject

StereochemistryClinical BiochemistryRamelteonPharmaceutical ScienceLigandsHeterocyclic Compounds 4 or More RingsBiochemistryMelatonin receptorMethylenedioxyEnamineMelatoninStructure-Activity Relationshipchemistry.chemical_compoundDrug DiscoverymedicineHumansIndeneMolecular Biologychemistry.chemical_classificationDose-Response Relationship DrugMolecular StructureReceptor Melatonin MT2HydrobromideReceptor Melatonin MT1Organic ChemistryHEK293 CellschemistryMolecular MedicineTricyclicmedicine.drug

description

Hexahydroindenopyridine (HHIP) is an interesting heterocyclic framework that contains an indene core similar to ramelteon. This type of tricyclic piperidines aroused our interest as potential melatoninergic ligands. Melatonin receptor ligands have applications in insomnia and depression. We report herein an efficient two-step method to prepare new HHIP by the reaction of an enamine with 3-bromopropylamine hydrobromide. Some synthesized compounds showed moderate affinity for melatonin receptors in the nanomolar or low micromolar range. Furthermore, the methylenedioxy HHIPs 2d (N-phenylacetamide) and 2f (N,N-diethylacetamide), exhibited high selectivity at MT1 or MT2 receptors, respectively, when compared with melatonin. It seems that the methylenedioxy group on the indene ring system and the N-acetamide substituent are important structural features to bind selectively MT1 or MT2 subtypes.

yearjournalcountryeditionlanguage
2014-04-16Bioorganic & Medicinal Chemistry Letters
https://doi.org/10.1016/j.bmcl.2014.05.053