| Autor: |
Siu M; Discovery Chemistry, Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, CA 92121, United States. siu.michael@gene.com, Johnson TO, Wang Y, Nair SK, Taylor WD, Cripps SJ, Matthews JJ, Edwards MP, Pauly TA, Ermolieff J, Castro A, Hosea NA, LaPaglia A, Fanjul AN, Vogel JE |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Jul 01; Vol. 19 (13), pp. 3493-7. Date of Electronic Publication: 2009 May 07. |
| DOI: |
10.1016/j.bmcl.2009.05.011 |
| Abstrakt: |
N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with improved physiochemical properties using a deletion strategy. This strategy allowed for further optimization of potency leading to the discovery of the clinical candidate PF-915275. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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