Structural highlights
Disease
[DHI1_HUMAN] Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
Function
[DHI1_HUMAN] 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).
Publication Abstract from PubMed
In this communication, human 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11beta-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.
The synthesis and SAR of novel diarylsulfone 11beta-HSD1 inhibitors.,Yan X, Wang Z, Sudom A, Cardozo M, DeGraffenreid M, Di Y, Fan P, He X, Jaen JC, Labelle M, Liu J, Ma J, McMinn D, Miao S, Sun D, Tang L, Tu H, Ursu S, Walker N, Ye Q, Powers JP Bioorg Med Chem Lett. 2010 Dec 1;20(23):7071-5. Epub 2010 Sep 29. PMID:20971000[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yan X, Wang Z, Sudom A, Cardozo M, DeGraffenreid M, Di Y, Fan P, He X, Jaen JC, Labelle M, Liu J, Ma J, McMinn D, Miao S, Sun D, Tang L, Tu H, Ursu S, Walker N, Ye Q, Powers JP. The synthesis and SAR of novel diarylsulfone 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):7071-5. Epub 2010 Sep 29. PMID:20971000 doi:10.1016/j.bmcl.2010.09.097
