Antiinflammatory activity of a series of substituted 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-diones
| العنوان: | Antiinflammatory activity of a series of substituted 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-diones |
|---|---|
| المؤلفون: | Peter J.S. Chiu, James J. Kaminski, Arthur S. Watnick, Tobias Massa, David J. Conn, Shing Chun Wong, Daniel M. Solomon, Marvin I. Siegel |
| المصدر: | Journal of Medicinal Chemistry. 32:1118-1127 |
| بيانات النشر: | American Chemical Society (ACS), 1989. |
| سنة النشر: | 1989 |
| مصطلحات موضوعية: | Purine, Naproxen, biology, Phosphodiesterase Inhibitors, Chemistry, Stereochemistry, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, medicine.disease, In vitro, Rats, Structure-Activity Relationship, chemistry.chemical_compound, Prenylation, Drug Discovery, biology.protein, medicine, Animals, Molecular Medicine, Structure–activity relationship, Potency, Cyclooxygenase Inhibitors, Stomach Ulcer, Cyclooxygenase, medicine.drug |
| الوصف: | A series of substituted analogues based on the novel 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-dione ring system have been synthesized and shown to exhibit antiinflammatory activity in the adjuvant-induced arthritis rat model (AAR). The activity exhibited by the pyrimidopurinediones in this model of chronic inflammation is comparable to that of their previously studied 2-oxo congeners, the 6-hydroxypyrimido[2,1-f]purine-2,4,8-(1H,3H,9H)-triones, the best of which show potency levels approximately equal to that of naproxen. On the basis of its potency in the AAR assay, 9-benzyl-2,3-dihydro-1,3-dimethyl-6-hydroxy-7-(3-methyl-2-butenyl) pyrimido-[2,1-f]purine-4,8(1H,9H)-dione was selected for further evaluation and found to exhibit cyclooxygenase inhibitory activity in the in vitro rat neutrophil model. With respect to side-effect liability, this prenylated derivative has been shown to be devoid of gastric ulcer inducing potential, as well as the ocular toxicity observed previously with the 2-oxo series. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f36bfa75f281ed5bd0c23c48d0edb0ba https://doi.org/10.1021/jm00125a029 |
| رقم الأكسشن: | edsair.doi.dedup.....f36bfa75f281ed5bd0c23c48d0edb0ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
|---|