A concise synthesis of 3-substituted-7-amino-6-carboxyl-8-azachromones |
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| Affiliation: | 1. State Key Laboratory of Bioactive Substances and Function of Natural Medicine & Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, PR China;2. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China;1. Laboratorio de Microbiología, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, 62209 Cuernavaca, Mexico;2. Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Blvd. del Maestro, s/n, Esq. Elías Piña, 88710 Reynosa, Mexico;3. Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiologia Aplicada, Universidad de Navarra, 31008 Pamplona, Spain;1. Department of Chemistry, Faculty of Science, Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia;2. Department of Chemistry, Faculty of Science, Port Said, Port Said University, Egypt;3. Department of Chemistry, Faculty of Science, Taif University, 888 Taif, Saudi Arabia;1. Department of Entomology, Kansas State University, Manhattan, KS 66506, USA;2. Research Institute of Resource Insect, Chinese Academy of Forestry, Kunming 650224, China;3. USDA-ARS-JWDSRC, PO Box 346/141 Exp Stn. Rd., Stoneville, MS 38776, USA;4. Hard Winter Wheat Genetics Research Unit, USDA-ARS, 4008 Throckmorton Hall, Kansas State University, Manhattan, KS 66506, USA;1. Department of Chemistry, Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg, Russian Federation;2. Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 620137 Ekaterinburg, Russian Federation;3. School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany |
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| Abstract: | We report on an approach to truncate the tricyclic 5H-chromeno[2,3-b]pyridin-5-one core of amlexanox, an approved drug under investigation for the treatment of obesity, to the bicyclic 4H-pyrano[2,3-b]pyridin-4-one (8-azachromone) core. A short, concise synthesis generates a key intermediate with requisite functionality on the pyridyl A-ring and iodo functionality on the 4-pyrone B-ring upon which palladium-catalyzed cross-coupling and subsequent reactions generate representative analogues. One of these shows a 14.2-fold increase in aqueous solubility over amlexanox. |
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| Keywords: | Obesity 8-Azachromone Palladium catalyzed cross-couplings |
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