| Autor: |
Yang BV; Bristol-Myers Squibb Company, Research and Development, Princeton, New Jersey 08543-4000, United States., Weinstein DS, Doweyko LM, Gong H, Vaccaro W, Huynh T, Xiao HY, Doweyko AM, McKay L, Holloway DA, Somerville JE, Habte S, Cunningham M, McMahon M, Townsend R, Shuster D, Dodd JH, Nadler SG, Barrish JC |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2010 Dec 09; Vol. 53 (23), pp. 8241-51. Date of Electronic Publication: 2010 Nov 12. |
| DOI: |
10.1021/jm100957a |
| Abstrakt: |
A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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