Discovery of pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists |
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| Affiliation: | 1. Department of Discovery Chemistry, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA;2. TCG Lifesciences Limited, Salt Lake Electronic Complex, Block BN, Plot 7, Sector V, Kolkata 700 091, India;3. Metabolic and Vascular Diseases, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA;1. Université de Toulouse, UPS CNRS, LHFA, UMR 5069, 118 Route de Narbonne, F-31062 Toulouse, France;2. Institutul de Chimie, Raluca Ripan, Universitatea Babeş-Bolyai, Str. M. Kogălniceanu, Nr: 1, RO-400084 Cluj-Napoca, Romania;3. Departamentul de Chimie Anorganică, Facultatea de Chimie şi Inginerie Chimică, Universitatea Babeş-Bolyai, Str. M. Kogălniceanu, Nr: 1, RO-400084 Cluj-Napoca, Romania;4. Université de Toulouse, UPS, Institut de Chimie de Toulouse, ICT-FR2599, 118 Route de Narbonne, F-31062 Toulouse, France;1. Department of Biotechnologies and Cellular Hematology, Sapienza University, Rome, Italy;2. Hematology, Policlinico S. Orsola, Bologna, Italy;3. Department of Hematology, University of Siena, Italy;4. Department of Clinical and Molecular Bio-Medicine, Section of Hematology and Oncology, University of Catania, Catania, Italy;5. Department of Health Sciences, University of Milano, Bicocca, Monza, Italy;6. Functional Unit of Hematology, University of Florence, Italy;7. Division of Haematology, Niguarda Hospital, Milan, Italy;8. CEINGE Biotecnologie Avanzate, Naples, Italy;9. Hematology 2, San Giovanni Battista Hospital and University, Turin, Italy;10. Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences of the University of Turin, Orbassano, Italy;11. Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section University of Bari, Italy;1. Department of Applied Physics, Nanjing University of Information Science and Technology, Nanjing 210044, China;2. Department of Condensed Matter Physics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 5, 121 16 Prague 2, Czech Republic;1. Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev 9, Sofia 1113, Bulgaria;2. Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria |
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| Abstract: | ![]()
We designed and synthesized a novel series of phenylamino- and phenoxy-substituted pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists. SAR studies indicated that electron-withdrawing substituents on the phenyl ring are important for potency and full efficacy. Compound 26 combined good potency with a promising pharmacokinetic profile in mice, and lowered the glucose excursion in mice in an oral glucose-tolerance test. |
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| Keywords: | GPR119 GPCR Agonist Type 2 diabetes Oral glucose tolerance test |
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