First selective CYP11B1 inhibitors for the treatment of cortisol-dependent diseases

ACS Medicinal Chemistry Letters

Volumn 2, Issue 1, 2011, Pages 2-6

  Hille, Ulrike E ^a   Zimmer, Christina ^a   Vock, Carsten A ^a   Hartmann, Rolf W ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

Cushing's syndrome, steroid hormone biosynthesis, steroid 11 hydroxylase, CYP11B1 inhibitor, CYP17, CYP19, CYP11B2, etomidate

Indexed keywords

ALDOSTERONE SYNTHASE; AROMATASE; CYTOCHROME P 450 CYP11B1 INHIBITOR; CYTOCHROME P450 17; CYTOCHROME P450 INHIBITOR; ETOMIDATE; KETOCONAZOLE; METYRAPONE; UNCLASSIFIED DRUG;

ARTICLE; CUSHING SYNDROME; DRUG POTENCY; DRUG STRUCTURE; DRUG SUBSTITUTION; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 78651515158     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml100071j     Document Type: Article

References (34)

1. Le Borgne, M.; Marchand, P.; Duflos, M.; Delevoye-Seiller, B.; Piessard-Robert, S.; Le Baut, G.; Hartmann, R. W.; Palzer, M. Synthesis and in vitro evaluation of 3-(1-Azolylmethyl)-1 H -indoles and 3-(1-azoly1-1- phenylmethyl)-1 H -indoles as inhibitors of P450 arom Arch. Pharm. 1997, 330, 141-145
2. Jacobs, C.; Frotscher, M.; Dannhardt, G.; Hartmann, R. W. 1-Imidazolyl (alkyl) substituted di-and tetrahydroquinolines and analogs. Syntheses and evaluation of dual inhibitors of thromboxane A2 synthase and aromatase J. Med. Chem. 2000, 43, 1841-1851
3. Leonetti, F.; Favia, A.; Rao, A.; Aliano, R.; Paluszcak, A.; Hartmann, R. W.; Carotti, A. Design, synthesis and 3D QSAR of novel potent and selective aromatase inhibitors J. Med. Chem. 2004, 47, 6792-6803
4. Gobbi, S.; Cavalli, A.; Rampa, A.; Belluti, F.; Piazzi, L.; Paluszcak, A.; Hartmann, R. W.; Recanatini, M.; Bisi, A. Lead optimization providing a series of flavone derivatives as potent nonsteroidal inhibitors of the cytochrome P450 aromatase enzyme J. Med. Chem. 2006, 49, 4777-4780
5. Dutta, U.; Pant, K. Aromatase inhibitors: Past, present and future in breast cancer therapy Med. Oncol. 2008, 25, 113-124
6. Zhuang, Y.; Wachall, B. G.; Hartmann, R. W. Novel imidazolyl and triazolyl substituted biphenyl compounds: Synthesis and evaluation as nonsteroidal inhibitors of human 17α-hydroxylase-C17,20-lyase(P450 17) Bioorg. Med. Chem. 2000, 8, 1245-1252
7. Leroux, F.; Hutschenreuter, T.; Charrière, C.; Scopelliti, R.; Hartmann, R. W. N -(4-Biphenylmethyl)imidazoles as potential therapeutics for the treatment of prostate cancer: metabolic robustness due to fluorine substition? Helv. Chim. Acta 2003, 86, 2671-2686
8. Hutschenreuter, T. U.; Ehmer, P. B.; Hartmann, R. W. Synthesis of hydroxy derivatives of highly potent non-steroidal CYP 17 inhibitors as potential metabolites and evaluation of their activity by a non cellular assay using recombinant human enzyme J. Enzyme Inhib. Med. Chem. 2004, 19, 17-32
9. Attard, G.; Reid, A. H.; A'Hern, R.; Parker, C.; Oommen, N. B.; Folkerd, E.; Messiou, C.; Molife, L. R.; Maier, G.; Thompson, E.; Olmos, D.; Sinha, R.; Lee, G.; Dowsett, M.; Kaye, S. B.; Dearnaley, D.; Kheoh, T.; Molina, A.; de Bono, J. S. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer J. Clin. Oncol. 2009, 27, 3742-3748
10. Picard, F.; Schulz, T.; Hartmann, R. W. 5-Phenyl substituted 1-methyl-2-pyridones and 4′-substituted biphenyl-4-carboxylic acids. Synthesis and evaluation as inhibitors of steroid-5α-reductase type 1 and 2 Bioorg. Med. Chem. 2002, 10, 437-448
11. Picard, F.; Baston, E.; Reichert, W.; Hartmann, R. W. Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and evaluation as inhibitors of steroid-5α-reductase type 1 and 2 Bioorg. Med. Chem. 2000, 8, 1479-1487
12. Baston, E.; Hartmann, R. W. N -substituted 4-(5-indolyl)benzoic acids. Synthesis and evaluation of steroid 5α-reductase type I and II inhibitory activity Bioorg. Med. Chem. Lett. 1999, 9, 1601-1606
13. Aggarwal, S.; Tharejaa, S.; Vermaa, A.; Bhardwaja, T. R.; Kumar, M. An overview on 5α-reductase inhibitors Steroids 2010, 75, 109-153
14. Bey, E.; Marchais-Oberwinkler, S.; Kruchten, P.; Frotscher, M.; Werth, R.; Oster, A.; Algul, Ö.; Neugebauer, A.; Hartmann, R. W. Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for treatment of estrogen dependent diseases Bioorg. Med. Chem. 2008, 16, 6423-6435 (Pubitemid 351783414)
15. Bey, E.; Marchais-Oberwinkler, S.; Werth, R.; Negri, M.; Al-Soud, Y.; Kruchten, P.; Oster, A.; Frotscher, M.; Birk, B.; Hartmann, R. W. Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes and aza-benzenes as potent and selective non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) J. Med. Chem. 2008, 51, 6725-6739
16. Frotscher, M.; Ziegler, E.; Marchais-Oberwinkler, S.; Kruchten, P.; Neugebauer, A.; Fetzer, L.; Scherer, C.; Müller-Vieira, U.; Messinger, J.; Thole, H.; Hartmann, R. W. Design, synthesis and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: Potent, selective and non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases J. Med. Chem. 2008, 51, 2158-2169 (Pubitemid 351503271)
17. Marchais-Oberwinkler, S.; Kruchten, P.; Frotscher, M.; Ziegler, E.; Neugebauer, A.; Bhoga, U.; Bey, E.; Müller-Vieira, U.; Messinger, J.; Thole, H.; Hartmann, R. W. Substituted 6-phenyl-2-naphthols. Potent and selective non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1): Design, synthesis, biological evaluation and pharmacokinetics J. Med. Chem. 2008, 51, 4685-4698
18. Siu, M.; Johnson, T. O.; Wang, Y.; Nair, S. K.; Taylor, W. D; Cripps, S. J.; Matthews, J. J.; Edwards, M. P.; Pauly, T. A.; Ermolieff, J.; Castro, A.; Hosea, N. A.; LaPaglia, A.; Fanjul, A. N.; Vogel, J. E. N -(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275 Bioorg. Med. Chem. Lett. 2009, 19, 3493-3497
19. Mornet, E.; Dupont, J.; Vitek, A.; White, P. C. Characterization of two genes encoding human steroid 11β-hydroxylase [P-450(11)β] J. Biol. Chem. 1989, 264, 20961-20967
20. Lucas, S.; Heim, R.; Negri, M.; Antes, I.; Ries, C.; Schewe, K. E.; Bisi, A.; Gobbi, S.; Hartmann, R. W. Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach J. Med. Chem. 2008, 51, 6138-6149
21. Heim, R.; Lucas, S.; Grombein, C. M.; Ries, C.; Schewe, K. E.; Negri, M.; Müller-Vieira, U.; Birk, B.; Hartmann, R. W. Overcoming undesirable CYP1A2 potency of pyridylnaphthalene type aldosterone synthase inhibitors: Influence of heteroaryl substitution on potency and selectivity J. Med. Chem. 2008, 51, 5064-5074
22. Voets, M.; Antes, I.; Scherer, C.; Müller-Vieira, U.; Biemel, K.; Barassin, C.; Marchais-Oberwinkler, S.; Hartmann, R. W. Heteroaryl substituted naphthalenes and structurally modified derivatives: Selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis J. Med. Chem. 2005, 48, 6632-6642
23. Ulmschneider, S.; Müller-Vieira, U.; Mitrenga, M.; Hartmann, R. W.; Marchais-Oberwinkler, S.; Klein, C. D. P.; Bureik, M.; Bernhardt, R.; Antes, I.; Lengauer, T. Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: Potent inhibitors of aldosterone synthase J. Med. Chem. 2005, 48, 1796-1805 (Pubitemid 40396312)
24. Ulmschneider, S.; Müller-Vieira, U.; Klein, C. D. P.; Antes, I.; Lengauer, T.; Hartmann, R. W. Synthesis and evaluation of (pyridylmethylene) tetrahydronaphthalenes/ -indanes and structurally modified derivatives: Potent and selective inhibitors of aldosterone synthase J. Med. Chem. 2005, 48, 1563-1575
25. Ries, C.; Lucas, S.; Heim, R.; Birk, B.; Hartmann, R. W. Selective aldosterone synthase inhibitors reduce aldosterone formation in vitro and in vivo J. Steroid Biochem. Mol. Biol. 2009, 116, 121-126
26. Lucas, S.; Heim, R.; Ries, C.; Schewe, K. E.; Birk, B.; Hartmann, R. W. In vivo active aldosterone synthase inhibitors with improved selectivity: Lead optimization providing a series of pyridine substituted 3,4-dihydro-1 H -quinolin-2-one derivates J. Med. Chem. 2008, 51, 8077-8087
27. Zolle, I. M.; Berger, M. L.; Hammerschmidt, F.; Hahner, S.; Schirbel, A.; Peric-Simov, B. New selective inhibitors of steroid 11β-hydroxylation in the adrenal cortex. Synthesis and structure-activity relationship of potent etomidate analogues J. Med. Chem. 2008, 51, 2244-2253
28. Diez, J. J.; Iglesias, P. Pharmacological therapy of Cushing's syndrome: Drugs and indications Mini Rev. Med. Chem. 2007, 7, 467-480
29. Roumen, L.; Peeters, J. W.; Emmen, J. M. A.; Beugels, I. P. E.; Custers, E. M. G.; de Gooyer, M.; Plate, R.; Pieterse, K.; Hilbers, P. A. J.; Smits, J. F. M.; Vekemans, J. A. J.; Leysen, D.; Ottenheijm, H. C. J.; Janssen, H. M.; Hermans, J. J. R. Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1 H -imidazoles as selective inhibitors of aldosterone synthase (CYP11B2) J. Med. Chem. 2010, 53, 1712-1725
30. Godefroi, E. F.; Janssen, P. A. J.; Van der Eycken, C. A. M.; Van Heertum, A. H. M. T.; Niemegeers, C. J. E. dl -1-(1-Arylalkyl)imidazole-5- carboxylate esters. A novel type of hypnotic agents J. Med. Chem. 1965, 8, 220-223
31. Ehmer, P. B.; Bureik, M.; Bernhardt, R.; Müller, U.; Hartmann, R. W. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): Screening in fission yeast and evaluation of selectivity in V79 cells J. Steroid Biochem. Mol. Biol. 2002, 81, 173-179
32. Denner, K.; Doehmer, J.; Bernhardt, R. Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional expression in COS-7 and V79 chinese hamster cells Endocr. Res. 1995, 21, 443-448
33. Ehmer, P. B.; Jose, J.; Hartmann, R. W. Development of a simple and rapid assay for the evaluation of inhibitors of human 17α-hydroxylase-C(17,20)- lyase (P450c17) by coexpression of P450c17 with NADPH-cytochrome-P450-reductase in Escherichia coli J. Steroid Biochem. Mol. Biol. 2000, 75, 57-63
34. Jagusch, C.; Negri, M.; Hille, U. E.; Hu, Q.; Bartels, M.; Jahn-Hoffmann, K.; Pinto-Bazurco Mendieta, M. A.; Rodenwaldt, B.; Müller-Vieira, U.; Schmidt, D.; Lauterbach, T.; Recanatini, M.; Cavalli, A.; Hartmann, R. W. Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure Bioorg. Med. Chem. 2008, 16, 1992-2010