| Structural highlights
Function
[DHI1_CAVPO] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).[1]
Publication Abstract from PubMed
The design and development of a series of highly selective pyrrolidine carboxamide 11beta-HSD1 inhibitors are described. These compounds including PF-877423 demonstrated potent in vitro activity against both human and mouse 11beta-HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11beta-HSD1 selective inhibitor 42.
The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors.,Cheng H, Hoffman J, Le P, Nair SK, Cripps S, Matthews J, Smith C, Yang M, Kupchinsky S, Dress K, Edwards M, Cole B, Walters E, Loh C, Ermolieff J, Fanjul A, Bhat GB, Herrera J, Pauly T, Hosea N, Paderes G, Rejto P Bioorg Med Chem Lett. 2010 May 1;20(9):2897-902. Epub 2010 Mar 10. PMID:20363126[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pu X, Yang K. Guinea pig 11beta-hydroxysteroid dehydrogenase type 1: primary structure and catalytic properties. Steroids. 2000 Mar;65(3):148-56. PMID:10699594
- ↑ Cheng H, Hoffman J, Le P, Nair SK, Cripps S, Matthews J, Smith C, Yang M, Kupchinsky S, Dress K, Edwards M, Cole B, Walters E, Loh C, Ermolieff J, Fanjul A, Bhat GB, Herrera J, Pauly T, Hosea N, Paderes G, Rejto P. The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2010 May 1;20(9):2897-902. Epub 2010 Mar 10. PMID:20363126 doi:10.1016/j.bmcl.2010.03.032
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