Modification of estrone at the 6, 16, and 17 positions: Novel potent inhibitors of 17β-hydroxysteroid dehydrogenase type 1

Journal of Medicinal Chemistry

Volumn 49, Issue 4, 2006, Pages 1325-1345

  Allan, Gillian M ^a   Lawrence, Harshani R ^a   Cornet, Josephine ^a   Bubert, Christian ^a   Fischer, Delphine S ^a   Vicker, Nigel ^a   Smith, Andrew ^a   Tutill, Helena J ^b   Purohit, Atul ^b   Day, Joanna M ^b   Mahon, Mary F ^c   Reed, Michael J ^b   Potter, Barry V L ^a  

^a University of Bath   (United Kingdom)

^b ST MARY S HOSPITAL   (United Kingdom)

^c University of Bath Claverton Down   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ESTRADIOL; ESTROGEN; ESTRONE DERIVATIVE; TESTOSTERONE 17BETA DEHYDROGENASE;

ARTICLE; BREAST CANCER; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION; HORMONE DEPENDENCE; IC 50; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

17-HYDROXYSTEROID DEHYDROGENASES; AMIDES; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; ESTRADIOL; ESTRONE; FEMALE; HUMANS; MODELS, MOLECULAR; NEOPLASMS, HORMONE-DEPENDENT; OXIMES; PYRAZOLONES; PYRIDINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33244477418     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050830t     Document Type: Article

References (55)

1. Ferlay, J.; Bray, F.; Pisani, P.; Parkin, D. M. IARC Cancerbase No. 5 version 2.0. IARC Press: Lyon, 2004.
2. Miller, W. R. Biological rationale for endocrine therapy in breast cancer. Best Pract. Res. Clin. Endoc. Metab. 2004, 18, 1-32.
3. Santner, S. J.; Feil, P. D.; Santen, R. J. In situ estrogen production via the estrone sulfatase pathway in breast tumors - relative importance versus the aromatase pathway. J. Clin. Endocrinol. Metab. 1984, 59, 29-33.
4. Reed, M. J.; Purohit, A.; Woo, L. W. L.; Newman, S. P.; Potter, B. V. L. Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr. Rev. 2005, 26, 171-202.
5. Mindnich, R.; Möller, G.; Adamski, J. The role of the 17 beta-hydroxysteroid dehydrogenases. J. Mol. Cell. Endocrinol. 2004, 218, 7-20. The 17β-HSD type 13 enzyme was disclosed at a workshop on 11β- and 17β-hydroxysteroid dehydrogenases: role in human disease, Germany 2005. Here 17β-HSD type 13 was identified as human retinal short chain dehydrogenase/reductase 3, PDB code 1YDE.
6. Puranen, T.; Poutanen, M.; Ghosh, D.; Vihko, R.; Vihko, P. Origin of substrate specificity of human and rat 17β-hydroxsteroid dehydrogenase type 1 using chimeric enzymes and site-directed substitutions. Endocrinology 1997, 138, 3532-3539.
7. Jin, J. Z.; Lin, S. X. Human estrogenic 17 beta-hydroxysteroid dehydrogenase: predominance of estrone reduction and its induction by NADPH. Biochem. Biophys. Res. Commun. 1999, 259, 489-493.
8. Spiers, V.; Green, A. R.; Atkin, S. L. Activity and gene expression of 17β-hydroxysteroid dehydrogenase type 1 in primary cultures of epithelial and stromal cells derived from normal and tumorous breast tissue: the role of IL8. J. Steroid Biochem. Mol. Biol. 1998, 67, 267-274.
9. Martel, C.; Rhéaume, E.; Takahashi, M.; Trudel, C.; Couët, J.; Luu-The, V.; Simard, J.; Labrie, F. Distribution of 17β-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. J. Steroid Biochem. Mol. Biol. 1992, 41, 597-603.
10. Penning, T. M. 17β-hydroxysteroid dehydrogenase: Inhibitors and inhibitor design. Endocrine-Related Cancer 1996, 3, 41-56.
11. Peltoketo, H.; Isomaa, V.; Maentausta, O.; Vihko, R. Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett. 1988, 239, 73-77.
12. Ghosh, D.; Pletnev, V. Z.; Zhu, D. W.; Wawrzak, Z.; Duax, W. L.; Pangborn, W.; Labrie, F.; Lin, S. X. Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 Å resolution. Structure 1995, 3, 503-513.
13. Breton, R.; Housset, D.; Mazza, C.; Fontecilla-Camps, J. C. The structure of a complex human 17β-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors. Structure 1996, 4, 905-915.
14. Azzi, A.; Reshe, P. H.; Zhu, D. W.; Campbell, R. L.; Labrie, F.; Lin, S. X. Crystal structure of human estrogenic 17β-hydroxysteroid dehydrogenase-1 complexed with 17β-estradiol. Nat. Struct. Biol. 1996, 3, 665-668.
15. Sawicki, M. W.; Erman, M.; Puranen, T.; Vihko, P.; Ghosh, D. Structure of the ternary complex of human 17β-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 840-845.
16. Qiu, W.; Campbell, R. L.; Gangloff, A.; Dupuis, P.; Boivin, R. P.; Tremblay, M. R.; Poirier, D.; Lin, S.-X. A concerted, rational design of type 1 17β hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity. FASEB J. 2002, 16, 1829-1830.
17. Poirier, D. Inhibitors of 17β-hydroxysteroid dehydrogenase. Curr. Med. Chem. 2003, 10, 453-477.
18. Sam, K.-M.; Boivin, R. P.; Tremblay, M. R.; Auger, S.; Poirier, D. C16 and C17 derivatives of estradiol as inhibitors of 17β-hydroysteroid dehydrogenase type 1: chemical synthesis and structure activity relationships. Drug Des. Discovery 1998, 15, 157-180.
19. Poirier, D.; Boivin, R. P.; Bérubé, M.; Lin, S.-X. Synthesis of a first estradiol-adenosine hybrid compound. Synth. Commun. 2003, 33, 3183-3192.
20. Hirvelä, L.; Johansson, N.; Koskimies, P.; Pentikäinen, O. T.; Nyrönen, T.; Salminen, T. A.; Johnson, M. S. Novel compounds and their use in therapy. PCT WO 2005032527, 2005.
21. Messinger, J.; Thole, H.-H.; Husen, B.; Van Steen, B. J.; Schneider, G.; Hulshof, J. B. E.; Koskimies, P.; Johansson, N.; Adamski, J. Novel 17beta hydroxysteroid dehydrogenase type 1 inhibitors. PCT WO 2005047303, 2005.
22. Vicker, N.; Lawrence, H. R. R.; Allan, G. M.; Bubert, C.; Fischer, D. S. M.; Purohit, A.; Reed, M. J.; Potter, B. V. L. Preparation of estranes as 17 β-hydroxysteroid dehydrogenase inhibitors. PCT WO 2004085457, 2004.
23. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res. 2000, 28, 235-242.
24. Fischer, D. S.; Allan, G. M.; Bubert, C.; Vicker, N.; Smith, A.; Tutill, H. J.; Purohit, A.; Wood, L.; Packham, G.; Mahon, M. F.; Reed, M. J.; Potter, B. V. L. E-Ring modified steroids as novel potent inhibitors of 17β-hydroxysteroid dehydrogenase type 1. J. Med. Chem. 2005, 48, 5749-5770.
25. Thomas, J. L.; LaRochelle, M. C.; Covey, D. F.; Strickler, R. C. Inactivation of human placental 17β,20α-hydroxysteroid dehydrogenase by 16-methylene estrone, an affinity alkylator enzymatically generated from 16-methylene estradiol-17β. J. Biol. Chem. 1983, 258, 19, 11500-11504.
26. Ringold, H. J.; Rosenkranz, G. 16-Methyl derivatives of estrone and estradiol. US 3,103,521, 1963.
27. Lawrence, H.; Vicker, N.; Allan, G. M.; Smith, A.; Mahon, M.; Tutill, H.; Purohit, A.; Reed, M. J.; Potter, B. V. L. Novel and potent 17β-hydroxysteroid dehydrogenase type 1 inhibitors. J. Med. Chem. 2005, 48, 2759-2762.
28. Schwenk, E.; Montclair, N. J. Oxygenated estrogenic hormones and method of preparing same. US 2,294,938, 1942.
29. Cambie, R. C.; Manning, T. D. R. Oxidation products of 3-methoxyoestral,3,5(10)-trien-17β-yl acetate. J. Chem Soc. C. 1968, 2603-2608.
30. Katzenellenbogen, J. A.; Myers, H. N.; Johnson, H. J. Reagents for photoaffinity labeling of estrogen binding proteins. Synthesis of some azide and diazo derivatives of estradiol, estrone and hexestrol. J. Org. Chem. 1973, 38, 3525-3533.
31. Pearson, A. J.; Han, G. R. Benzylic oxidation using tert-butyl hydroperoxide in the presence of chromium hexacarbonyl. J. Org. Chem. 1985, 50, 2791-2792.
32. Fischer, D. S.; Woo, L. W. L.; Mahon, M. F.; Purohit, A.; Reed, M. J.; Potter, B. V. L. D-ring modified estrone derivatives as novel potent inhibitors of steroid sulfatase. Bioorg. Med. Chem. 2003, 11, 1685-1700.
33. Hejaz, H. A. M.; Purohit, A.; Mahon, M. F.; Reed, M. J.; Potter, B. V. L. Synthesis and biological activity of the superestrogen (E)-17-oximino-3-O- sulfamoyl-1,3,5(10)-estratriene: X-ray crystal structure of (E)-17-oximino-3- hydroxy-1,3,5(10)-estratriene. J. Med. Chem. 1999, 42, 3188-3192.
34. Tanabe, M.; Peters, R. H.; Chao, W.-R.; Shigeno, K. Estrone sulfamate inhibitors of estrone sulfatase, and associated pharmaceutical compositions and methods of use. WO 9933858, 1999.
35. Paquette, L. A.; Dahnke, K.; Doyon, J.; He, W.; Wyant, K.; Friedrich, D. Regioselective conversion of cycloalkanones to vinyl bromides with 1,2-functionality transportation. A general stratagem. J. Org. Chem. 1991, 56, 21, 6199-6205.
36. Nicolai, E.; Cure, G.; Goyard, J.; Kirchner, M.; Teulon, J. M.; Versigny, A.; Cazes, M.; Vironeoddos, A.; Caussade, F.; Cloarec, A. Synthesis and angiotensin-II receptor agonist activity of C-linked pyrazole derivatives. Chem. Pharm. Bull 1994, 42, 8, 1617-1630.
37. Fevig, T. L.; Mao, M. K.; Katzenellenbogen, J. A. Estrogen receptor binding tolerance of 16α-substituted estradiol derivatives. Steroids 1988, 51, 5-6, 471-497.
38. Tapolcsányi, P.; Wölfling, J.; Falkay, G.; Márki, A.; Minorics, R.; Schneider, G. Synthesis and receptor-binding examination of 16-hydroxymethyl-3-17-estradiol stereoisomers. Steroids 2002, 67, 371-377.
39. Labaree, D. C.; Reynolds, T. Y.; Hochberg, R. B. Estradiol-16α- carboxylic acid esters as locally active estrogens. J. Med. Chem. 2001, 44, 1802-1814.
40. McArdle, P. ORTEX2.1 - a 1677-atom veriosn of ORTEP with automatic cell outline and cell packing for use on a PC. J. Appl. Crystallogr. 1994, 27, 438-439.
41. Goto, G.; Yoshikoda, K.; Hiraga, K. The Serini reaction of 16,17-dihydroxysteroid monoacetates. Tetrahedron 1974, 30, 2107-2114.
42. Minu, M.; Jindal, D. P. Synthesis and biological activity of 16-arylidene derivatives of estrone and estrone methyl ether. Indian. J. Chem. Sect. B. 2003, 42, 166-172.
43. Boivin, R. P.; Luu-The, V.; Lachance, R.; Labrie, F.; Poirier, D. Structure-activity relationships of 17α-derivatives of estradiol as inhibitors of steroid sulfatase. J. Med. Chem. 2000, 43, 4465-4478.
44. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
45. Klebe, G. Comparative Molecular Similarity Indices: CoMSIA. Perspect. Drug Disc. Des. 1998, 12-14, 87-104.
46. Lemmen, C.; Lengauer, T. Time-efficient flexible superposition of medium-sized molecules. J. Comput.-Aided Mol. Des. 1997, 11, 357-368.
47. Lemmen, C.; Lengauer, T.; Klebe, G. FlexS: A method for fast flexible ligand superposition. J. Med. Chem. 1998, 41, 4502-4520.
48. Cramer, R. D., III; Bunce, J. D.; Patterson, D. E.; Frank, I. E. Cross-validation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR Studies. Quant. Struct-Act. Relat. 1988, 7, 18-25.
49. Zhu, B. T.; Lee, A. J. NADPH-dependent metabolism of 17β-estradiol and estrone to polar and nonpolar metabolites by human tissues and cytochrome P450 isoforms. Steroids 2005, 70, 225-244.
50. Duncan, L. J.; Reed, M. J. The role and proposed mechanism by which oestradiol 17β-hydroxysteroid dehydrogenase regulates breast tumour oestrogen concentrations. J. Steroid Biochem. Mol. Biol. 1995, 55, 565-572.
51. Regan, B. M.; Hayes, F. N. 17- and 17a-Aza-D-homosteroids. J. Am. Chem. Soc. 1956, 78, 639-643.
52. Matkovics, B.; Tarodi, B.; Balaspiri, L. Rearrangement of steroids, VII. Schmidt reaction and Beckmann rearrangement of estrone and its derivatives. Acta C. Acad. Sci. Hung. 1974, 80, 79-87.
53. Sweet, F.; Boyd, J.; Medina, O.; Konderski, L.; Murdock, G. L. Hydrogen bonding in steroidogenesis - studies on new heterocyclic analogues of estrone that inhibit human estradiol 17 beta-dehydrogenase. Biochem. Biophys. Res. Commun. 1991, 180, 1057-1063.
54. Sheldrick, G. M. Phase annealing in SHELX-90: Direct methods for larger structures. Acta Crystallogr. 1990, A46 (6), 467-473.
55. Sheldrick, G. M. SHELXL-97, a computer program for crystal structure refinement, University of Göttingen. 1997.