Design of novel multiple-acting ligands towards SERT and 5-HT2C receptors |
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| Affiliation: | 1. Department of Medicinal Chemistry, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;2. Department of Structural Chemistry, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;3. Department of In Vitro Sciences, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;4. Department of Pharmacology, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;5. Department of Drug Metabolism, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;6. Department of Basic Pharmaceutical Sciences, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;7. Department of Oncology, Merck & Co., 33 Avenue Louis Pasteur, Boston, MA 02115, USA;1. Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States;2. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States;3. The Scripps Research Institute Molecular Screening Center, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States;4. Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States;1. Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;2. Department of Neuroscience, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;3. Pharmaceutical R&D, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;4. Department of Comparative Biology and Safety Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;5. Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;6. Analytical Research & Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States;1. Pharmaceutical Research Institute, 01-793 Warszawa, Poland;2. Department of Chemistry, The University of Warsaw, 02-093 Warszawa, Poland;3. Institute of Organic Chemistry of the Polish Academy of Sciences, 01-224 Warszawa, Poland;1. Boehringer Ingelheim Pharma GmbH & Co. KG, Department of Medicinal Chemistry, Birkendorfer Str. 65, 88397 Biberach an der Riss, Germany;2. Boehringer Ingelheim Pharma GmbH & Co. KG, Department of Cardiometabolic Research, Birkendorfer Str. 65, 88397 Biberach an der Riss, Germany;3. Boehringer Ingelheim Pharma GmbH & Co. KG, Department of Drug Discovery Support Research Germany, Birkendorfer Str. 65, 88397 Biberach an der Riss, Germany |
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| Abstract: | This Letter describes our attempts to elaborate dually acting compounds possessing serotonin re-uptake transporter inhibitor and serotonin 5-HT2C receptor antagonist properties. A novel series of 1,3-diphenylureas and N-phenylbenzamides have thus been prepared and evaluated. Based on its in vitro and in vivo activities, as well as pharmacokinetic profile, compound 16a was identified as a lead compound. The synthesis and structure–activity relationship of this series of compounds is presented herein. |
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| Keywords: | Designed multiple ligands SERT inhibitor |
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