Heterocyclic aminopyrrolidine derivatives as melatoninergic agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 24; pp. 4381 - 4384
• Main Authors: SUN, Li-Qiang, JIE CHEN, ORTIZ, Astrid, MOLSTAD, David, RYAN, Elaine, YELESWARAM, Krishnaswamy, CEN XU, GUANGLIN LUO, MATTSON, Ronald J, EPPERSON, James R, DESKUS, Jeffrey A, LI, Wen-Sen, TAKAKI, Katherine, HODGES, Donald B, IBEN, Lawrence, MAHLE, Cathy D
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 15.12.2003
• Subjects: 3T3 Cells; Aminoquinolines - chemical synthesis; Aminoquinolines - pharmacology; Animals; Biological and medical sciences; Cloning, Molecular; Colforsin - pharmacology; Cyclic AMP - metabolism; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - pharmacology; Humans; Kinetics; Ligands; Medical sciences; Melatonin - agonists; Melatonin - pharmacology; Mice; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptor, Melatonin, MT1 - drug effects; Receptor, Melatonin, MT1 - metabolism; Receptor, Melatonin, MT2 - drug effects; Receptor, Melatonin, MT2 - metabolism; Recombinant Proteins - metabolism; Structure-Activity Relationship; Intravenous administration; Rat; Nitrogen heterocycle; Oxygen heterocycle; Pyrrole derivatives; MC1 melanocortin receptor; Structure activity relation; Bicyclic compound; Peptidergic receptor; Ureas; Aromatic compound; Chemical synthesis; Dog; MC2 melanocortin receptor; Fissipedia; Carnivora; Rodentia; Oral administration; Bioavailability; Circadian rhythm; In vitro; In vivo; Vertebrata; Mammalia; Cell line; Mouse; Animal; Benzofuran derivatives; Pharmacokinetics; Fibroblast
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.09.030

A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin receptors with low vasoconstrictive activity.