Synthesis and evaluation of novel fused pyrimidine derivatives as GPR119 agonists |
| |
| Affiliation: | 1. National Engineering Research Center for Manufacturing Technology of TCM Solid Preparation, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China;2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;1. Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O.B.: 17, H-1525 Budapest, Hungary;2. Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O.B.: 17, H-1525 Budapest, Hungary;1. Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1 bd. 3, Moscow 119991, Russia;2. FSBSI “Chumakov FSC R&D IBP RAS”, Moscow 108819, Russia;3. Sechenov First Moscow State Medical University, Moscow 119991, Russia;4. Institute of Physiologically Active Compounds, Severny Proezd 1, Chernogolovka, Moscow Region 142432, Russia;5. Volgograd State Technical University, Lenina Avenue 28, Volgograd 400005, Russia;1. Department of Chemistry, Faculty of Science, Karadeniz Technical University, 61080 Trabzon, Turkey;2. Department of Molecular Biology and Genetics, Gaziosmanpaşa University, 60250 Tokat, Turkey;3. Department of Chemistry, Faculty of Arts and Sciences, Recep Tayyip Erdoğan University, 53100 Rize, Turkey;4. Faculty of Pharmacy, Karadeniz Technical University, 61080 Trabzon, Turkey;1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA;3. Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA;4. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215, USA;5. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;6. Daegu-Gyeongbuk Medical Innovation Foundation, Republic of Korea;7. Chemical Kinomics Research Center, Korea Institute of Science and Technology, Republic of Korea;8. KU-KIST Graduate School of Converging Science and Technology, Korea University, Republic of Korea;1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 21009, China;2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China |
| |
| Abstract: | A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16, 19, 26, 28, 42) bearing endo-N-Boc-nortropane amine and fluoro-substituted aniline exhibited better EC50 values (0.27–1.2 μM) though they appeared to be partial agonists. |
| |
| Keywords: | Tetrahydroquinazoline Dihydrocyclopentapyrimidine GPR119 agonists |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
