| Autor: |
Ashton, M. J., Lawrence, C., Karlsson, J.-A., Stuttle, K. A. J., Newton, C. G., Vacher, B. Y. J., Webber, S., Withnall, M. J. |
| Zdroj: |
Journal of Medicinal Chemistry; December 6, 1996, Vol. 39 Issue: 25 p4888-4896, 9p |
| Abstrakt: |
The synthesis and anti-inflammatory potencies of a new class of 17β-thioalkyl-16α,17α-ketal and -acetal androstanes are described. This new class of steroids was made by fragmentation of 2-thioxo-1,2-dihydropyrid-1-yl esters of the corresponding 17-acids to the 17-radical. The radical generated was trapped using a variety of radicophilic disulfides, giving a steroidal D-ring having acetal or ketal functionality at C-16 and C-17, together with a sulfide link at C-17. Compounds from this series bind to the glucocorticoid receptor with high potency and are functional agonists as measured by their ability to induce tyrosine aminotransferase activity in a rat hepatic cell line in vitro. These 17β-thioalkyl androstanes potently inhibit Sephadex-induced rat lung inflammation when administered directly into the airways. The high topical potency, together with a low propensity to induce systemic glucocorticoid-like side effects (rat thymus involution), provides the present compounds with a high degree of airway selectivity compared with currently available inhaled glucocorticoids. The presently described 17β-thioalkyl-16α,17α-ketal androstanes may be useful for therapies for inflammatory diseases such as asthma. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
