New melatonin (MT1/MT2) ligands: Design and synthesis of (8,9-dihydro-7H-furo[3,2-f]chromen-1-yl) derivatives |
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| Institution: | 1. Univ. Lille Nord de France, F-59000 Lille, France;2. UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France;3. Biotechnologies, Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France;4. Unité de Recherche Chimie Neurosciences, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France;5. Unité de Recherches et Découvertes en Neurosciences, Institut de Recherches Servier, 78290 Croissy-sur-Seine, France;1. School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa;2. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Groote Schuur Hospital, Observatory 7925, South Africa;1. Istituto di Biostrutture e Bioimmagini—CNR, Via Mezzocannone 16, 80134 Napoli, Italy;2. Dipartimento di Scienze Chimiche, Università di Napoli ‘Federico II’, 80126 Napoli, Italy;3. Dipartimento delle Scienze Biologiche, Università di Napoli ‘Federico II’, 80134 Napoli, Italy;1. Health Physics Division, Institute of Nuclear Energy Research, PO Box 3-10, Longtan 325, Taiwan, ROC;2. Department of Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan, ROC;3. Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC;1. Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States;2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States;3. The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States;1. Bioanalytical Research Laboratory for NO, Eicosanoids and Oxidative Stress, Centre of Pharmacology and Toxicology, Hannover Medical School, 30623 Hannover, Germany;2. Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany |
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| Abstract: | Herein we describe the synthesis of novel tricyclic analogues issued from the rigidification of the methoxy group of the benzofuranic analogue of melatonin as MT1 and MT2 ligands. Most of the synthesized compounds displayed high binding affinities at MT1 and MT2 receptors subtypes. Compound 6b (MT1, Ki = 0.07 nM; MT2, Ki = 0.08 nM) exhibited with the vinyl 6c and allyl 6d the most interesting derivatives of this series. Functional activity of these compounds showed full agonist activity with EC50 in the nanomolar range. Compounds 6a (EC50 = 0.8 nM and Emax = 98%) and 6b (EC50 = 0.2 nM and Emax = 121%) exhibited good pharmacological profiles. |
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| Keywords: | Benzofuran derivatives Melatonin |
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