Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/- indanes and structurally modified derivatives: Potent and selective inhibitors of aldosterone synthase

Journal of Medicinal Chemistry

Volumn 48, Issue 5, 2005, Pages 1563-1575

  Ulmschneider, Sarah ^a   Müller Vieira, Ursula ^a   Klein, Christian D ^a   Antes, Iris ^b   Lengauer, Thomas ^b   Hartmann, Rolf W ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b MAX PLANCK INSTITUTE FOR INFORMATICS   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

(PYRIDYLMETHYLENE)INDANE DERIVATIVE; (PYRIDYLMETHYLENE)TETRAHYDRONAPHTHALENE DERIVATIVE; 5 [(5 CHLORO 2,3 DIHYDRO 1H INDEN 1 YLIDENE)METHYL] 1H IMIDAZOLE; ALDOSTERONE SYNTHASE; ALDOSTERONE SYNTHASE INHIBITOR; AROMATASE; CYTOCHROME P450 17; ENZYME INHIBITOR; FADROZOLE; INDAN DERIVATIVE; KETOCONAZOLE; NAPHTHALENE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITOR INTERACTION; HUMAN; IC 50; MOLECULAR MODEL; NONHUMAN; REACTION ANALYSIS; SCHIZOSACCHAROMYCES POMBE; STRUCTURE ACTIVITY RELATION;

ADRENAL CORTEX HORMONES; ALDOSTERONE SYNTHASE; AROMATASE; CELL LINE; ESCHERICHIA COLI; HUMANS; INDANS; MICROSOMES; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PLACENTA; PYRIDINES; SCHIZOSACCHAROMYCES; STEREOISOMERISM; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDRONAPHTHALENES;

EID: 14944355617     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0492397     Document Type: Article

References (57)

1. Kawamoto, T.; Mitsuuchi, Y.; Toda, K.; Yokoyama, Y.; Miyahara, K.; Miura, S.; Ohnishi, T.; Ichikawa, Y.; Nakao, K.; Imura, H. Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 1458-1462.
2. Brilla, C. G. Renin-angiotensin-aldosterone system and myocardial fibrosis. Cardiovasc. Res. 2000, 47, 1-3.
3. Pitt, B.; Remme, W.; Zannad, F.; Neaton, J.; Martinez, F.; Roniker, B.; Bittman, R.; Hurley, S.; Kleiman, J.; Gatlin, M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 2003, 348, 1309-1321.
4. Pitt, B.; Zannad, F.; Remme, W. J.; Cody, R.; Castaigne, A.; Perez, A.; Palensky, J.; Wittes, J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 1999, 341, 709-717.
5. Christ, M.; Grimm, W.; Maisch, B. Significance of aldosterone antagonist therapy. Internist (Berlin) 2004, 45, 347-354.
6. Delyani, J. A. Mineralocorticoid receptor antagonists: The evolution of utility and pharmacology. Kidney Int. 2000, 57, 1408-1411.
7. 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.
8. Hartmann, R. W.; Müller, U.; Ehmer, P. B. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur. J. Med. Chem. 2003, 38, 363-366.
9. Baumann, C. K.; Aebi, S. Aromatase inhibitors in the adjuvant therapy of breast carcinomas. Ther. Umsch. 2004, 61, 359-364.
10. Pilon, C.; Mulatero, P.; Barzon, L.; Veglio, F.; Garrone, C.; Boscaro, M.; Sonino, N.; Fallo, F. Mutations in CYP11B1 gene converting 11beta-hydroxylase into an aldosterone-producing enzyme are not present in aldosterone-producing adenomas. J. Clin. Endocrinol. Metab. 1999, 84, 4228-4231.
11. Wisconsin Package Version 10.1, Genetics Computer Group (GCG), Madison, WI.
12. Ulmschneider, S.; Müller-Vieira, U.; Mitrenga, M.; Hartmann, R. W.; Oberwinkler-Marchais, S.; Klein, C. D.; Bureik, M.; Bernhardt, R.; Antes, I.; Lengauer, T. Synthesis and evaluation of imidazolylmethylene- tetrahydronaphthalenes and imidazolylmethylene-indanes: Potent inhibitors of aldosterone synthase. J. Med. Chem. 2004, in press (available online: http://dx.doi.org/10.1021/jm049600p).
13. Dowsett, M.; Stein, R. C.; Mehta, A.; Coombes, R. C. Potency and selectivity of the nonsteroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clin. Endocrinol. (Oxford) 1990, 32, 623-634.
14. Demers, L. M.; Melby, J. C.; Wilson, T. E.; Lipton, A.; Harvey, H. A.; Santen, R. J. The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis. J. Clin. Endocrinol. Metab. 1990, 70, 1162-1166.
15. Bureik, M.; Hubel, K.; Dragan, C. A.; Scher, J.; Becker, H.; Lenz, N.; Bernhardt, R. Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) inhibitors. Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension. Mol. Cell. Endocrinol. 2004, 217, 249-254.
16. Hartmann, R. W. Selective inhibition of steroidogenic P450 enzymes: Current status and future perspectives. Eur. J. Pharm. Sci. 2 1994, 15-16.
17. Van Wauwe, J. P.; Janssen, P. A. Is there a case for P-450 inhibitors in cancer treatment? J. Med. Chem. 1989, 32, 2231-2239.
18. El Ahmad, Y.; Laurent, E.; Maillet, P.; Talab, A.; Teste, J. F.; Dokhan, R.; Tran, G.; Ollivier, R. New benzocycloalkylpiperazines, potent and selective 5-HT1A receptor ligands. J. Med. Chem. 1997, 40, 952-960.
19. Hercouet, A.; Le Corre, M. Triphenylphosphonium bromide: A convenient and quantitative source of gaseous hydrogen bromide. Synth. Commun. 1988, 157-158.
20. Reimann, E.; Hargasser, E. Synthese von cis-9,11a-dimethyl-4,5,6,6a,7a,8, 9,10,11,11a-decahydro-7H-naphtho(1,8-fg)isochmolinen (Synthesis of cis-9,11a-dimethyl-4,5,6,6a,7a,8,9,10,11,11a-decahydro-7H-naphtho(1,8-fg) isoquinolines). Arch. Pharm. 1989, 327, 159-164.
21. Donbrow, M. Cyclisation and debenzylation of m-benzyloxypropionic acid as competitive reactions. J. Chem. Soc. 1959, 1613-1615.
22. Budhram, R. S.; Palaniswamy, V. A.; Eisenbraun, E. J. Steric effects in the synthesis of 1,7-dialkylindanes. J. Org. Chem. 1986, 51, 1402-1406.
23. Rabjohn, M. 2,3-Dimethoxycinnamic acid. Org. Synth. Collect. 1963, 327-329.
24. Musso, D. L.; Cochran, F. R.; Kelley, J. L.; McLean, E. W.; Selph, J. L.; Rigdon, G. C.; Orr, G. F.; Davis, R. G.; Cooper, B. R.; Styles, V. L.; Thompson, J. B.; Hall, W. R. Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity. J. Med. Chem. 2003, 46, 399-408.
25. Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P. A new convenient preparation of 2-, 4-, and 5-thiazolecarboxaldehydes and their conversion into the corresponding carbonitrile N-oxides: Synthesis of 3-thiazolyl-isoxazoles and 3-thiazolylisoxazolines. Synthesis 1987, 11, 998-1001.
26. Rho, T.; Abuh, Y. F. One pot synthesis of pyrimidine-5-carboxaldehyde and ethyl pyrimidine-5-carboxylate by utilizing pyrimidin-5-yl-lithium. Synth. Commun. 1994, 24, 253-256.
27. 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, 27, 443-448.
28. Denner, K.; Vogel, R.; Schmalix, W.; Doehmer, J.; Bernhardt, R. Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 chinese hamster cells and their application for testing of potential inhibitors. Pharmacogenetics 1995, 5, 89-96.
29. Thompson, E. A., Jr.; Siiteri, P. K. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J. Biol. Chem. 1974, 249, 5364-5372.
30. Hartmann, R. W.; Batzl, C. Aromatase inhibitors. Synthesis and evaluation of mammary tumor inhibiting activity of 3-alkylated 3-(4-aminophenyl) piperidine-2,6-diones. J. Med. Chem. 1986, 29, 1362-1369.
31. Hutschenreuter, T. U.; Ehmer, P. B.; Hartmann, R. W. Synthesis of hydroxy derivatives of highly potent nonsteroidal CYP17 inhibitors as potential metabolites and evaluation of their activity by a non cellular assay using recombinant enzyme. J. Enzyme Inhib. Med. Chem. 2004, 19, 17-32.
32. Williams, P. A.; Cosme, J.; Ward, A.; Angove, H. C.; Matak Vinkovic, D.; Jhoti, H. Crystal structure of human cytochrome P4502C9 with bound warfarin. Nature 2003, 424, 464-468.
33. Böttner, B.; Bernhardt, R. Changed ratios of glucocorticoids/ mineralocorticoids caused by point mutations in the putative I-helix regions of CYP11B1 and CYP11B2. Endocr. Res. 1996, 22, 455-461.
34. Böttner, B.; Schrauber, H.; Bernhardt, R. Engineering a mineralocorticoid- to a glucocorticoid-synthesizing cytochrome P450. J. Biol. Chem. 1996, 271, 8028-8033.
35. Häusler, A.; Monnet, G.; Borer, C.; Bhatnagar, A. S. Evidence that corticosterone is not an obligatory intermediate in aldosterone biosynthesis in the rat adrenal. J. Steroid Biochem. 1989, 34, 567-570.
36. Bhatnagar, A. S.; Häusler, A.; Schieweck, K.; Lang, M.; Bowman, R. Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new nonsteroidal aromatase inhibitor. J. Steroid Biochem. Mol. Biol. 1990, 37, 1021-1027.
37. De Coster, R.; Caers, I.; Coene, M. C.; Amery, W.; Beerens, D.; Haelterman, C. Effects of high dose ketoconazole therapy on the main plasma testicular and adrenal steroids in previously untreated prostatic cancer patients. Clin. Endocrinol. (Oxford) 1986, 24, 657-664.
38. Albrecht, R.; Schröder, E. Chemotherapeutic nitro-heterocyclic compounds. 3. Preparation of nitrofurfurylidene-, nitrothienylidene- and nitropyrrolylmethylene-derivatives of substitued 1-indanones and 1.2.3.4-tetrahydro-1-naphthalenones. Justus Liebigs Ann. Chem. 1970, 736, 110-125.
39. Horwell, D. C.; Howson, W.; Nolan, W. P.; S., R. G.; Rees, D. C.; Willems, H. M. G. The design of dipeptidic helical mimetics, part I: The synthesis of 1,6-disubstituted indanes. Tetrahedron 1995, 51, 203-216.
40. Takeuchi, R.; Yasue, H. Rhodium complex-catalyzed desilylative cyclocarbonylation of 1-aryl-2-(trimethylsilyl)acetylenes: A new route to 2,3-dihydro-1H-inden-1-ones. J. Org. Chem. 1993, 58, 5386-5392.
41. Luo, J.-K.; Castle, S. L.; Castle, R. N. The synthesis of difluoro(1) benzothieno〈2,3-c〉quinolines and their N-methyl quaternary salts. J. Heterocycl. Chem. 1990, 27, 2047-2052.
42. Yuzikhin, O. S.; Vasil'ev, A. V.; Rudenko, A. P. Oxidation of aromatic compounds: VIII. Oxidative dehydrodimerization of cinnamic acid derivatives in the system CF3COOH-CH2C12-PbO2. Russ. J. Org. Chem. 2000, 36, 1743-1754.
43. Olivier, M.; Marechal, E. Etude de monomeres halogenes et de leur polymerisation cationique. I.- Synthese de divers fluoroindenes (Study on halogenated monomers and their cationic polymerisation. Synthesis of several fluoro-indenes). Bull. Soc. Chim. Fr. 1973, 3092-3095.
44. Houghton, R. P.; Voyle, M.; Price, R. Reactions of coordinated ligands. Part 10. Rhodium-catalysed cyclisation of 3-(2-fluorophenyl)propanols to chromans. J. Chem. Soc., Perkin. Trans. 1 1984, 5, 925-931.
45. Becke, A. D. Density-functional exchange-energy approximation with the correct asymptotic behaviour. Phys. Rev. A 1988, 38, 3098-3100.
46. Lee, C. L.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 1988, 37, 785-789.
47. Dunning, T. H., Jr. Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J. Chem. Phys. 1989, 90, 1007-1023.
48. Moller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev. 1934, 46, 618.
49. Flükiger, P.; Lüthi, H. P.; Portmann, S.; Weber, J. MOLEKEL 4.0, Swiss Center for Scientific Computing, Manno (Switzerland), 2000.
50. Humphrey, W.; Dalke, A.; Schulten, K. VMD-Visual Molecular Dynamics. J. Mol. Graph. 1996, 14, 33-38.
51. Ginalski, K.; Elofsson, A.; Fischer, D.; Rychlewski, L. 3D-Jury: A simple approach to improve protein structure predictions. Bioinformatics 2003, 19, 1015-1018.
52. Schwede, T.; Kopp, J.; Guex, N.; Peitsch, M. C. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003, 31, 3381-3385.
53. Rodriguez, R.; Chinea, G.; Lopez, N.; Pons, T.; Vriend, G. Homology modeling, model and software evaluation: Three related resources. Bioinformatics 1998, 14, 523-528.
54. Petrey, D.; Xiang, Z.; Tang, C. L.; Xie, L.; Gimpelev, M.; Mitros, T.; Soto, C. S.; Goldsmith-Fischman, S.; Kernytsky, A.; Schlessinger, A.; Koh, I. Y.; Alexov, E.; Honig, B. Using multiple structure alignments, fast model building, and energetic analysis in fold recognition and homology modeling. Proteins 2003, 53 Suppl 6, 430-435.
55. Canutescu, A. A.; Shelenkov, A. A.; Dunbrack, R. L., Jr. A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci. 2003, 12, 2001-2014.
56. Lindahl, E.; Hess, B.; van der Spoel, D. GROMACS 3.0: A package for molecular simulation and trajectory analysis. J. Mol. Mod. 2001, 7, 306-317.
57. Hindle, S. A.; Rarey, M.; Buning, C.; Lengauer, T. Flexible docking under pharmacophore type constraints. J. Comput. Aid. Mol. Des. 2002, 16, 129-149.