Synthesis and evaluations of selective COX-2 inhibitory effects: Benzo[d]thiazol analogs |
| |
| Institution: | 1. Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan 316022, PR China;2. Key Laboratory of Natural Resource of the Changbai Mountain and Functiaonal Molecules, Ministry of Education, Yanbian University, Jilin Yanji 133000, China;1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China;2. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Panum, Maersk Tower, Blegdamsvej 3B, 2200 Copenhagen N, Denmark;3. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China;1. Department of Chemistry, Department of Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, The Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States;2. Cessation Therapeutics LLC, 3031 Tisch Way Ste 505, San Jose, CA 95128, United States;1. College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea;2. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea;3. Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea;4. Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea;5. Department of Biomedical Research Center, Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of Korea;1. University of Navarra, School of Pharmacy and Nutrition, Department of Pharmaceutical Technology and Chemistry, Irunlarrea 1, 31008 Pamplona, Spain;2. Institute of Tropical Health, University of Navarra, Pamplona, Spain;3. Department of Biochemistry and Molecular Biology, Universidad de Alcalá, Carretera Madrid-Barcelona km 33,600, E-28871 Alcalá de Henares, Madrid, Spain;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October University of Modern Sciences and Arts (MSA), 6th of October City, Giza, Egypt;3. Biomedical Sciences Program, Zewail City of Science and Technology, University of Science and Technology, October Gardens, 6th of October City, 12578, Giza, Egypt;4. Drug Design and Discovery Laboratory, Helmy Institute of Science and Technology, Zewail City of Science and Technology, 12578, Cairo, Egypt;1. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China;2. China Crop Protection Industry Association, Beijing 100723, China |
| |
| Abstract: | A series of benzod]thiazole analogs were synthesized and evaluated for their anti-inflammatory and analgesic effects. Using an ear edema model, except for compounds 2k, 2m-2q and 3a, other compounds showed the anti-inflammatory effects. Among them, compounds 2c, 2d, and 2g showed the best anti-inflammatory activity (inhibition rate: 86.8%, 90.7% and 82.9%, respectively). By the acetic acid-induced abdominal writhing test, except for compounds 2e, 2l, 2m, 2o, 2p and 3a, other compounds showed the analgesic effects with inhibition rate values of 51.9–100% (2a-2r) and 68.6–100% (3a-3g). Next, compounds 2c, 2d, 2g, 3d, 3f, 3g that displayed the excellent anti-inflammatory and analgesic activities were evaluated for their inhibitory effect against ovine COX-1 and COX-2. Compounds 2c, 2d, 2g, 3d, 3f, 3g were weak inhibitors of the COX-1 isozyme but exhibited the moderate COX-2 isozyme inhibitory effects IC50 from 0.28 to 0.77 μM and COX-2 selectivity indexes (SI: 18.6 to 7.2). This benzod]thiazole moiety will be proved to be of great significance for developing more potent COX-2 inhibitors. |
| |
| Keywords: | Synthesis Anti-inflammatory Analgesic COX-2 inhibitors |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
