Hydroxysteroid Dehydrogenase Type 1 Inhibitors

Rollinger et al. used a previously experimentally validated pharmacophore model for lip-hydroxysteroid dehydrogenase type 1 (lip-HSDl) to screen the DIOS database [95]. On the basis of the reported plant constituents in the hit list, triterpenoids 

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Schuster, D., Maurer, E.M., Laggner, C., Nashev, L.G., Wilckens, T, Langer, T, and Odermatt, A. (2006) The discovery of new 1 Ibeta-hydroxysteroid dehydrogenase type 1 inhibitors by common feature pharmacophore modeling and virtual screening. Journal of Medicinal Chemistry, 49, 3454-3466. 

Adie, J.E. (2010) Stmcture-based dmg design of lip-hydroxysteroid dehydrogenase type 1 inhibitors. PhD. thesis. University of Edinburgh. 

Barf, T., Williams, M. (2006) Recent progress in llb-hydroxysteroid dehydrogenase type 1 (llb-HSDl) inhibitor development. Drugs Future 31(3), 231-243. 

Olson, S., Balkovec, J., Gao, Y. -D, et al. (2004) Selective inhibitors of llfi-hydroxysteroid dehydrogenase type 1. Adamantyl triazoles as pharmacological agents for the treatment of metabolic syndrome. Keystone Symp Abst X2-239. 

Barf T, Vallgarda J, Emond R, et al. Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and seleotive inhibitors of the 11 (3-hydroxysteroid dehydrogenase type 1. J Med Chem 2002 45 3813-3815. 

Mundt, S. et al. Development and application of a scintillation proximity assay (SPA) for identification of selective inhibitors of 1 ip-hydroxysteroid dehydrogenase type 1. Assay Drug Dev. Technol. 2005, 3, 367-375. 

Fig. 25 Mouse liver microsome (MLM) half-life data for piperidine-based 11 P-hydroxysteroid dehydrogenase type I (lip-HSDl) inhibitors...

Monoester 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-l-carboxylic acid 59 (Figure 4.17) is a building block of many potential therapeutic candidates for inhibitors of 11-p-hydroxysteroid dehydrogenase type 1 enzyme and their use in the treatment of non-insulin-dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and CNS disorders. It is also required for the synthesis of 5-hydroxytryptamine receptor agonists, useful for the treatment of anxiety disorders and schizophrenia [90,91]. 

Andrews, R C., Rooyackers, O., Walker, B. R (2003) Effects of the llfi-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab 88, 285-291. 

U. (2006) Active site variability of type 1 llb-hydroxysteroid dehydrogenase revealed by selective inhibitors and cross-species comparisons. Mol Cell Endocrinol 248, 26-33. 

FIGURE 11.54 Libraries of type 3 17 3-hydroxysteroid dehydrogenase inhibitors. (From Maltais, R., Luu-The, V., and Poirier, D., Parallel solid-phase synthesis of 3 3-peptido-3 -hydroxy-5 -androstan-17-one derivatives for inhibition of type 3 17P-hydroxysteroid dehydrogenase, Bioorg. Med. Chem., 9, 3101, 2001 Maltais, R., Luu-The, V., and Poirier, D., Synthesis and optimization of a new family of type 17P-hydroxysteroid dehydrogenase inhibitors by parallel liquid phase chemistry, J. Med. Chem., 45, 640, 2002.)... 

Maltais, R., Luu-The, V., and Poirier, D., Synthesis and optimization of a new family of type 17 3-hydroxysteroid dehydrogenase inhibitors by parallel liquid phase chemistry, J. Med. Chem., 45, 640, 2002. 

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