17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives. Novel steroidal inhibitors of human cytochrome C17,20-lyase (P45017α)

Journal of Medicinal Chemistry

Volumn 40, Issue 20, 1997, Pages 3297-3304

  Ling, Yang Zhi ^a   Li, Ji Song ^a,b   Liu, Yang ^a   Kato, Katsuya ^a   Klus, Gregory T ^a   Brodie, Angela ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANE DERIVATIVE; CYTOCHROME P450; CYTOCHROME P450 INHIBITOR; IMIDAZOLE DERIVATIVE; ISOXAZOLE DERIVATIVE; KETOCONAZOLE; LYASE; PYRAZOLE DERIVATIVE;

ANDROGEN SYNTHESIS; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVITY; HUMAN; HUMAN CELL; MALE; MICROSOME; NONHUMAN; PROSTATE CANCER; RAT; STRUCTURE ACTIVITY RELATION; TESTIS;

ANDROSTENES; ANIMALS; ENZYME INHIBITORS; HUMANS; IMIDAZOLES; ISOXAZOLES; MALE; MICROSOMES; PYRAZOLES; RATS; RATS, SPRAGUE-DAWLEY; STEROID 17-ALPHA-HYDROXYLASE; STRUCTURE-ACTIVITY RELATIONSHIP; TESTIS;

EID: 0030828474     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970337k     Document Type: Article

References (34)

1. Ayub, M.; Level, M. Inhibition of Testicular 17α-Hydroxylase and 17,20-Lyase but not 3-Hydroxysteroid Dehydrogenase- Isomerase or 17-Hydroxysteroid Oxidoreductase by Ketoconazole and Other Imidazole drugs. J. Steroid Biochem. 1987, 28, 521-531.
2. (a) Nakajin, S.; Takahashi, K.; Shinoda, M. Inhibitory Effect and Interaction of Stanozolol with Pig Testicular Cytochrome P-450 (17α-Hydroxylase/C17,20-Lyase). Chem. Pharm. Bull. (Tokyo) 1989, 37, 1855-1858.
3. (b) Nakajin S.; Takahashi, K.; Shinoda, M. Inhibitory Effect and Spectral Changes on Pig Testicular Cytochrome P-450 (17α-Hydroxylase/C17,20-lyase) by 20β-Hydroxy-C21Steroids. Yakugaku Zasshi 1988, 108, 1188-1195.
4. 17,20Lyase). Biochem. Biophys. Res. Commun. 1989, 162, 1571-1577.
5. Jarman, M.; Barrie, S. E.; Deadman, J. J.; Houghton, J.; McCague, R. Hydroxyperfluoroazobenzenes: Novel Inhibitors of Enzymes of Androgen Biosynthesis. J. Med. Chem. 1990, 33, 2452-2455.
6. McCague, R.; Rowlands, M. G.; Barrie, S. E.; Houghton, J. Inhibition of Enzymes of Estrogen and Androgen Biosynthesis by Ester of 4-Pyridylacetic acid. J. Med. Chem. 1990, 33, 3050-3055.
7. 17α-(17α-Hydroxylase-C17,20-lyase): Potential Agents for the Treatment of Prostatic Cancer. J. Med. Chem. 1995, 38, 2463-2471.
8. 17(20) Lyase with C-17-Heteroaryl Steroids. Bioorg. Med. Chem. 1996, 4, 1411-1420.
9. Njar, V. C. O.; Hector, M.; Hartmann, R. W. 20-Amino and 20,-21-Aziridinyl Pregnene Steroids: Development of Potent Inhibitors of 17α-Hydroxylase/C17,20-Lyase (P450 17). Bioorg. Med. Chem. 1996, 4, 1447-1453.
10. 16 Steroids; Inhibitors of 17α-Hydroxylase/17,20-Lyase (17α-Lyase). Bioorg. Med. Chem. Lett. 1996, 6, 2777-2782.
11. Trachtenberg, J. Ketoconazole Therapy in Advanced Prostatic Cancer. J. Urol. 1984, 132, 61-63.
12. Williams, G.; Kerle, D. J.; Doble, A.; Dunlop, H.; Smith, C.; Allen, J.; Yeo, T.; Blooms, S. R. Objective Responses to Ketoconazole Therapy in Patients with Relapsed Progressive Prostatic Cancer. Br. J. Urol. 1986, 58, 45-51.
13. Stoner, E. The Clinical Development of a 5α-Reductase Inhibitor, Finasteride. J. Steroid Biochem. Mol. Biol. 1990, 37, 375-378.
14. Geller, J. Effects of Finasteride, a 5α-Reductase Inhibitor on Prostate Tissue Androgens and Prostatic-Specific Antigen. J. Clin. Endocnnol. Metab. 1990, 71, 1552-1555.
15. Li, J.; Li, Y.; Son, C.; Brodie, A. Inhibition of Androgen Synthesis by 22-Hydroximino-23,24-bisnor-4-cholen-3-one. The Prostate 1995, 26, 140-150.
16. Li, J.; Li, Y.; Son, C.; Banks, P.; Brodie, A. 4-Pregnen-3-one-20β-carboxaldehyde: A Potent Inhibitor of 17α-Hydroxylase. J. Steroid Biochem. Mol. Biol. 1992, 42, 313-320.
17. Li, J. S.; Li, Y.; Son, Chong.; Brodie, A. Synthesis and Evaluation of Pregnane Derivatives as Inhibitors of Human Testicular 17α-Hydroxylase/C17,20-Lyase. J. Med. Chem. 1996, 39, 4335-4339.
18. Lang, M.; Batzl, Ch.; Furet, P.; Bowman, R.; Hausler, A.; Bhatnager, A. Structure-activity Relationships and Binding Model of Novel Aromatase Inhibitors. J. Steroid Biochem. Mol. Biol. 1993, 44, 421-428.
19. Lipton, A.; Harvey H. A.; Demers L. M.; Hanagan, J. R.; Mulagha, M. T.; Kochak, G. M.; Fitzsimmons, S.; Sanders, S. I.; Santen, R. J. A phase I trial of CGS 16949A, A New Aromatase Inhibitor. Cancer 1990, 65, 1279-1285.
20. Schipper, E. S.; Day, A. R. Imidazoles and Condensed Imidazoles. In Heterocyclic Compounds Vol. 5; Elderfiled, R. C., Ed.; John Wiley & Sons, Inc: New York, 1967; pp 194-29.
21. Ronig, K. (Assignor to Searle Co.), 4-(Cyclopentanopolyhydrophenanthr-17-yl) Imidazoles and Derivatives Thereof, U.S. Patent 2,664,423, 1953; Chem. Abstr. 1953, 49, 7608e.
22. Ronig, K. (Assignor to Searle Co.), 4-(Cyclopentanopolyhydrophenanthr-17-yl) Imidazoles and Derivatives Thereof, U.S. Patent 2,664,423, 1953; Chem. Abstr. 1953, 49, 7608e.
23. Mille, J. S.; Bowas, A.; Djerassi, C.; Ringold, H. F. Steroids, CXXXVII, Synthesis of a New Class of Potent Cortisol Hormones. 6α,9α-Difluoro-16α-hydroxyprednisolone and its Acetonide. J. Am. Chem. Soc. 1960, 82, 3399.
24. Barrie, S. E.; Potter, G. A.; Goddard, P. M.; Haynes, B. P.; Dowsett, M.; Jarman, M. Pharmacology of Novel Steroidal Inhibitors of Cytochrome P450 17α (17α-hydroxylase/C17,20-Lyase) J. Steroid Biochem. Mol. Biol. 1994, 50, 267-273.
25. Glazier, E. R. Bromination with Cupric Bromide. II. Bromination in the Presence of an Olefinic Bond. J. Org. Chem. 1962, 27, 4397-4399.
26. Ling, Y.; Li, J.; Klus, G. T.; Son C.; Marat, K.; Brodie, A. M. H. Unpublished results.
27. Doorenbos, N. J.; Milewich. L.; 17β-Isoxazolyl and 17β-Pyrazolyl Steroids from 3β-Hydroxy-21-formyl-pregn-5-en-20-one. Structural Assignments. J. Org. Chem. 1966, 31, 3193-3199.
28. Pelc, B.; Hodkova, J. Steroid Derivatives. LX. Androstane Derivatives Substituted by Pyrazole Ring in Position 17. Collect. Czech. Chem. Commun. 1969, 34, 442-450.
29. Ohta, G.; Kosh, K.; Obata, K. Investigations on Steroids XI. Synthesis of Steroidal Oxazole, Imidazole, and Triazole, Chem. Pharm. Bull. 1968, 16, 1487-1497.
30. Yanaihara, T.; Troen, P. Studies of the Human Testia. 1. Biosynthetic Pathways for Androgen Formation in Human Testicular Tissue In Vitro. J. Clin. Endocrinol. Metab. 1972, 34, 783-792.
31. Klus, G. T.; Nakamura, J.; Li, J.; Ling, Y.; Son, C.; Kemppained, J. A.; Wilson, E. M.; Brodie, A. M. H. Growth Inhibition of Human Prostate Cells In Vitro by Novel Inhibitors of Androgen Synthesis. Cancer Res. 1996, 56, 4956-4964.
32. Danishefsky, S.; Nagasawa, K. Conversion of Androstenolone to Pregnenolone. J. Org. Chem. 1975, 40, 1989-1990.
33. 17α (17α-hydroxylase-17,20-lyase). J. Chem. Soc., Perkin Trans. 1 1994, 263-267.
34. Lowry, O. H.; Roseborough, N. S.; Farr, A. L.; Randall, R. S. Protein Measurement with the Folin Phenol Reagent. J. Biol. Chem. 1951, 193, 265-275.