Imidazolylmethylbenzophenones as highly potent aromatase inhibitors

Journal of Medicinal Chemistry

Volumn 50, Issue 15, 2007, Pages 3420-3422

  Gobbi, Silvia ^a   Cavalli, Andrea ^a   Negri, Matthias ^b   Schewe, Katarzyna E ^b   Belluti, Federica ^a   Piazzi, Lorna ^a   Hartmann, Rolf W ^b   Recanatini, Maurizio ^a   Bisi, Alessandra ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b SAARLAND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; AROMATASE INHIBITOR; BENZOPHENONE DERIVATIVE; CYTOCHROME P450 17; EXEMESTANE; IMIDAZOLE DERIVATIVE; IMIDAZOLYLMETHYLBENZOPHENONE DERIVATIVE; LETROZOLE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER INHIBITION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ESTROGEN BLOOD LEVEL; HUMAN; POSTMENOPAUSE;

AROMATASE INHIBITORS; BENZOPHENONES; BINDING SITES; HUMANS; IMIDAZOLES; MICROSOMES; MODELS, MOLECULAR; PLACENTA; PROTEIN BINDING; STEROID 17-ALPHA-HYDROXYLASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34547607018     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0702938     Document Type: Article

References (21)

1. Howell, A. New developments in the treatment of postmenopausal breast cancer. Trends Endocrinol. Metab. 2005, 16, 420-428.
2. Brueggemeier, R. W.; Hackett, J. C.; Diaz-Cruz, E. S. Aromatase inhibitors in the treatment of breast cancer. Endocr. Rev. 2005, 26, 331-345.
3. Mouridsen, H.; Gershanovich, M.; Sun, Y.; Perez-Carrion, R.; Boni, C.; Monnier, A.; Apffelstaedt, J.; Smith, R.; Sleeboom, H. P.; et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: Analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J. Clin. Oncol. 2003, 21, 2101-2109.
4. Saberi, M. R.; Vinh, T. K.; Yee, S. W.; Griffiths, B. J. N.; Evans, P. J.; Simons, C. Potent CYP19 (aromatase) 1-[(benzofuran-2-yl)-(phenylmethyl) pyridine, -imidazole, and -triazole inhibitors: Synthesis and biological evaluation. J. Med. Chem. 2006, 49, 1016-1022.
5. Su, B.; Diaz-Cruz, E. S.; Landini, S.; Brueggemeier, R. W. Novel sulfonanilide analogues suppress aromatase expression and activity in breast cancer cells independent of COX-2 inhibition. J. Med. Chem. 2006, 49, 1413-1419.
6. Lézé, M. P.; Le Borgne, M.; Pinson, P.; Palusczak, A.; Duflos, M.; Le Baut, G.: Hartmann, R. W. Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: Potent and selective aromatase inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 1134-1137.
7. Gobbi, S.; Cavalli, A.; Rampa, A.; Belluti, F.; Piazzi, L.; Palusczak, 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.
8. Recanatini, M.; Bisi, A.; Cavalli, A.; Belluti, F.; Gobbi, S.; Rampa, A.; Valenti, P.; Palzer, M.; Palusczak, A.; Hartmann, R. W. A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase. J. Med. Chem. 2001, 44, 672-680.
9. 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.
10. Hutschenreuter, T. U.; Ehmer, P. B.; Hartmann, R. W. Synthesis of hydroxy derivatives of highly potent nonsteroidal CYP 17 inhibitors as potential metabolites and evaluation of their activity by a non cellular assay using recombinant human enzyme. J. Enzyme Inhib. 2004, 19, 17-32.
11. Lang, M.; Batzl, C.; Furet, P.; Bowman, R.; Hausler, A.; Bhatnagar, A. S. Structure-activity relationships and binding model of novel aromatase inhibitors. J. Steroid Biochem. Mol. Biol. 1993, 44, 421-428.
12. Favia, A. D.; Cavalli, A.; Masetti, M.; Carotti, A.; Recanatini, M. Three-dimensional model of the human aromatase enzyme and density functional parameterization of the iron-containing protoporphyrin IX for molecular dynamics study of heme-cysteinato cytochromes. Proteins 2006, 62, 1074-1087.
13. Bottegoni, G.; Cavalli, A.; Recanatini, M. A comparative study on the application of hierarchical-agglomerative clustering approaches to organize outputs of reiterated docking runs. J. Chem. Inf. Model. 2006, 46, 852-862.
14. Bottegoni, G.; Rocchia, W.; Recanatini, M.; Cavalli, A. AC1AP, Autonomous hierarchical agglomerative cluster analysis based protocol to partition conformational datasets. Bioinformatics 2006, 22, e58-e65.
15. Recanatini, M.; Cavalli, A.; Valenti, P. Nonsteroidal aromatase inhibitors: recent advances. Med. Res. Rev. 2002, 22, 282-304.
16. Recanatini, M.; Cavalli, A. Comparative molecular field analysis of nonsteroidal aromatase inhibitors: An extended model for two different structural classes. Bioorg. Med. Chem. 1998, 6, 377-388.
17. Cavalli, A.; Bisi, A.; Bertucci, C.; Rosini, C.; Paluszcak, A.; Gobbi, S.; Giorgio, E.; Rampa, A.; Belluti, F.; Piazzi, L.; Valenti, P.; Hartmann, R. W.; Recanatini, M. Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J. Med. Chem. 2005, 48, 7282-7289.
18. Graham-Lorence, S.; Amarneh, B.; White, R. E.; Peterson, J. A.; Simpson, E. R. A three-dimensional model of aromatase cytochrome P450. Protein Sci. 1995, 4, 1065-1080.
19. Koymans, L. M.; Moereels, H.; Van den Bossche, H. A molecular model for the interaction between vorozole and other non-steroidal inhibitors and human cytochrome P450 19 (P450 aromatase). J. Steroid Biochem. Mol. Biol. 1995, 53, 191-197.
20. Cavalli, A.; Greco, G.; Novellino, E.; Recanatini, M. Linking CoMFA and protein homology models of enzyme-inhibitor interactions: An application to nonsteroidal aromatase inhibitors. Bioorg. Med. Chem. 2000, 8, 2771-2780 and references therein.
21. Kao, Y. C.; Korzekwa, K. R.; Laughton, C. A.; Chen, S. Evaluation of the mechanism of aromatase cytochrome P450. A site-directed mutagenesis study. Eur. J. Biochem. 2001, 268, 243-251.