Novel non-steroidal inhibitors of human 11β-hydroxysteroid dehydrogenase type 1

Journal of Steroid Biochemistry and Molecular Biology

Volumn 104, Issue 3-5, 2007, Pages 123-129

  Vicker, Nigel ^a   Su, Xiangdong ^a   Ganeshapillai, Dharshini ^a   Smith, Andrew ^a   Purohit, Atul ^b   Reed, Michael J ^b   Potter, Barry V L ^a  

^a University of Bath   (United Kingdom)

^b Sterix Ltd   (United Kingdom)

Author keywords

11 HSD1 inhibitors; Diabetes; Hydroxysteroid dehydrogenase; Metabolic syndrome; Obesity

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE; 11BETA HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITOR; 3 CHLORO 2 METHYL N (9 OXO 9H FLUOREN 3 YL)BENZENESULFONAMIDE; 3,5 DICHLORO N (2 METHYLBENZOTHIAZOL 5 YL)BENZAMIDE; 4 PROPYL N (2 THIOPHEN 2 YL ETHYL)BENZENESULFONAMIDE; BVT 14225; ENZYME INHIBITOR; MK 544; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DIABETES MELLITUS; DRUG DESIGN; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; METABOLIC SYNDROME X; MOLECULAR MODEL; OBESITY;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; BENZAMIDES; BENZIMIDAZOLES; BINDING SITES; CELLS, CULTURED; DRUG EVALUATION; ENZYME INHIBITORS; FLUORENES; HUMANS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; SULFONAMIDES; THIAZOLES; THIOPHENES;

EID: 34250171175     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2007.03.023     Document Type: Article

References (37)

1. Edwards C.R., Stewart P.M., Burt D., Brett L., McIntyre M.A., Sutanto W.S., De Kloet E.R., and Monder C. Localization of 11β-hydroxy steroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet 332 (1988) 986-989
2. Tomlinson J.W., Walker E.A., Bujalska I.J., Draper N., Lavery G.G., Cooper M.S., Hewison M., and Stewart P.M. 11β-Hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr. Rev. 25 (2004) 831-866
3. Alberts P., Engblom L., Edling N., Forsgren M., Klingstrom G., Larsson C., Ronquist-Nii L., Ohman B., and Abrahmsen L. Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia 45 (2002) 1528-1532
4. Walker B.R., Connacher A.A., Lindsay M., Webb D.J., and Edwards C.R.W. Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J. Clin. Endocrinol. Metab. 80 (1995) 3155-3159
5. Kotelevtsev Y.V., Brown R.W., Fleming S., Kenyon C., Edwards C.R.W., Seckl J.R., and Mullins J.J. Hypertension in mice lacking 11β-hydroxysteroid dehydrogenase type 2. J. Clin. Invest 103 (1999) 683-689
6. Wang M. Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 for the treatment of metabolic syndrome. Curr. Opin. Investigat. Drugs 7 (2006) 319-323
7. Chapman K.E., Gilmour J.S., Coutinho A.E., Savill J.S., and Seckl J.R. 11β-Hydroxysteroid dehydrogenase type 1-a role in inflammation?. Mol. Cell. Endocrinol. 248 (2006) 3-8
8. Hermanowski-Vosatka A., Balkovec J.M., Cheng K., Chen H.Y., Hernandez M., Koo G.C., Le Grand C.B., Li Z., Metzger J.M., Mundt S.S., Noonan H., Nunes C.N., Olson S.H., Pikounis B., Ren N., Robertson N., Schaeffer J.M., Shah K., Springer M.S., Strack A.M., Strowski M., Wu K., Wu T.J., Xiao J., Zhang B.B., Wright S.D., and Thieringer R. 11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. J. Exp. Med. 202 (2005) 517-527
9. Holmes M.C., and Seckl J.R. The role of 11β-hydroxysteroid dehydrogenases in the brain. Mol. Cell. Endocrinol. 248 (2006) 9-14
10. Seckl J.R., Yau J.L.W., and Holmes M.C. The role of 11β-hydroxysteroid dehydrogenases in the regulation of corticosteroid activity in the brain. Techniques Behav. Neural Sci. Handbook Stress Brain, Part 1 15 (2005) 313-328
11. Fotsch C., Askew B.C., and Chen J.J. 11β-Hydroxysteroid dehydrogenase-1 as a target for metabolic diseases. Expert Opin. Ther. Pat. 54 (2005) 289-303
12. B.V.L. Potter, A. Purohit, M.J. Reed, N. Vicker, Use of glycyrrhetinic acid and progesterone derivatives which inhibit 11β-hydroxysteroid dehydrogenase as medicaments. WO072084 (2002).
13. Vicker N., Su X., Lawrence H., Cruttenden A., Purohit A., Reed M.J., and Potter B.V.L. A novel 18β-glycyrrhetinic acid analogue as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 2. Bioorg. Med. Chem. Lett. 14 (2004) 3263-3267
14. Su X., Lawrence H., Ganeshapillai D., Cruttenden A., Purohit A., Reed M.J., and Potter B.V.L. Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases. Bioorg. Med. Chem. 12 (2004) 4439-4457
15. N. Vicker, X. Su, D. Ganeshapillai, A. Purohit, M.J. Reed, B.V.L. Potter, Inibitors of 11β-hydroxy steroid dehydrogenase type 1 and type 2. PCT Int. Appl. WO037251 (2004).
16. N. Vicker, X. Su, D. Ganeshapillai, A. Purohit, M.J. Reed, B.V.L. Potter, Preparation of phenyl carboxamide and sulphonamide derivatives for use in inhibition of 11β-hydroxysteroid dehydrogenase. PCT Int. Appl. WO042513 (2005).
17. N. Vicker, X. Su, D. Ganeshapillai, A. Purohit, M.J. Reed, B.V.L. Potter, Phenylsulphonamide derivatives for use as 11beta-hydroxysteroid dehydrogenase inhibitors. PCT Int. Appl. WO103023 (2005).
18. Su X., Vicker N., Ganeshapillai D., Smith A., Purohit A., Reed M.J., and Potter B.V.L. Benzothiazole derivatives as novel inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. Mol. Cell. Endocrinol. 248 (2006) 214-217
19. G. Mathis, C. Dumont, D. Aspe, M. Foyentin, E.J.-P. Jolu, D. Nuti, Method for amplifying a signal emitted by a luminescent compound. WO9201225 (1992).
20. Mathis G. Rare earth cryptates and homogeneous fluoroimmunoassays with human sera. Clin. Chem. 39 (1993) 1953-1959
21. Bujalska I., Shimojo M., Howie A., and Stewart P.M. Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue. Steroids 62 (1997) 77-82
22. Odermatt A., Arnold P., Stauffer A., Frey B., Frey F.J., and Felix J. The N-terminal anchor sequences of 11β-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. J. Biol. Chem. 274 (1999) 28762-28770
23. Schweizer R.A.S., Atanasov A.G., Frey B.M., and Odermatt A. A rapid screening assay for inhibitors of 11β-hydroxysteroid dehydrogenases (11β-HSD): flavanone selectively inhibits 11β-HSD1 reductase activity. Mol. Cell. Endocrinol. 212 (2003) 41-49
24. M.R. Degraffenreid, X. He, J.P. Powers, D. Sun, X. Yan, Preparation of aryl sulphonamides as inhibitors of hydroxysteroid dehydrogenases (HSDs). PCT Int. Appl. WO063247 (2005).
25. K. Amrein, D. Hunziker, B. Kuhn, A. Mayweg, W. Neidhart, Preparation of arylpyridine derivatives useful for the treatment and prophylaxis of diabetes, obesity, eating disorders, dyslipidemiae, and hypertension. PCT Int. Appl. WO010546 (2006).
26. Zhang J., Osslund T.D., Plant M.H., Clogston C.L., Nybo R.E., Xiong F., Delaney J.M., and Jordan S.R. Crystal structure of murine 11β-hydroxysteroid dehydrogenase 1: an important therapeutic target for diabetes. Biochemistry 44 (2005) 6948-6957
27. Ogg D., Elleby B.N., Norstroem C., Stefansson K., Abrahmsen L., Oppermann U., and Svensson S. The crystal structure of guinea pig 11β-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions. J. Biol. Chem. 280 (2005) 3789-3794
28. Hosfield D.J., Wu Y., Skene E.J., Hilgers M., Jennings A., Snell G.P., and Aertgeerts K. Conformational flexibility in crystal structures of human 11β-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation. J. Biol. Chem. 280 (2005) 4639-4648
29. Sorensen B., Winn M., Rohde J., Shuai Q., Wang J., Fung S., Monzon K., Chiou W., Stolarik D., Imade H., Pan L., Deng X., Chovan L., Longenecker K., Judge R., Qin W., Brune M., Camp H., Frevert E.U., Jacobson P., and Link J.T. Adamantane sulfone and sulfonamide 11β-HSD1 Inhibitors. Bioorg. Med. Chem. Lett. 17 (2007) 527-532
30. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., and Bourne P.E. The protein data bank. Nucl. Acids Res. 28 (2000) 235-242
31. Hult M., Shafqat N., Elleby B., Mitschke D., Svensson S., Forsgren M., Barf T., Vallgarda J., Abrahmsen L., and Oppermann U. Active site variability of type 1 11β-hydroxysteroid dehydrogenase revealed by selective inhibitors and cross-species comparisons. Mol. Cell. Endocrinol. 248 (2006) 26-33
32. http://www.htrf-assays.com.
33. Halgren T.A. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comp. Chem. 20 (1999) 730-748
34. Sybyl Version 7.0, Tripos Inc., 1699 South Hanley RD., St. Louis, Missouri 63144, USA.
35. Jones G., Willett P., Glen R.C., Leach A.R., and Taylor R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 267 (1997) 727-748
36. Barf T., Vallgårda J., Emond R., Häggstrom G.K., Nygren A., Larwood V., Mosialou E., Axelsson K., Olsson R., Engblom L., Edling N., Rönquist-Nii Y., Öhman B., Alberts P., and Abrahmsén L. Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11β-hydroxysteroid dehydrogenase Type 1. J. Med. Chem. 45 (2002) 3813-3815
37. Schuster D., Maurer E.M., Laggner C., Lyubomir G.N., Wilckens T., Langer T., and Odermatt A. The discovery of new 11β-hydroxysteroid dehydrogenase type 1 inhibitors by common feature pharmacophore modelling and virtual screening. J. Med. Chem. 45 (2006) 3454-3466