Efficient construction of 6-azasteroids: Dual inhibitors of steroidal 5α-reductase

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 23, 1998, Pages 3291-3294

  Sharp, Matthew J ^a   Fang, Francis G ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 AZAANDROST 4 EN 3 ONE DERIVATIVE; AZASTEROID; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS;

EID: 0032401197     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00611-8     Document Type: Article

References (21)

1. 1. For reviews, see: (a) Liang, T.; Rasmusson, G. H.; Brooks, J. R. J. Steroid Biochem. 1983, 19, 385.
2. (b) Frye, S. V. Curr. Pharm. Des. 1996, 2, 59.
3. (c) Kenny, B.; Ballard, S.; Blagg, J.; Fox, D. J. Med. Chem. 1997, 40, 1293
4. 2. Russell, D. W.; Wilson, J. D. Annu. Rev. Biochem. 1994, 63, 25.
5. 3. Gormley, G. J.; Stoner, E.; Bruskewitz, R. C.; Imerato-McGinley, J.; Walsh, P. C.; McConnell, J. D.; Andriole, G. L.; Geller, J.; Bracken, B. R.; Tenover, J. S.; Vaughan, E. D.; Pappas, F.; Taylor, A.; Binkowitz, B.; Ng, J. N. Engl. J. Med. 1992, 327, 1185.
6. 4. Frye, S. V.; Haffner, C. D.; Maloney, P. R.; Mook, R. A.; Dorsey, G. F.; Hiner, R. N.; Batchelor, K. W.; Bramson, H. N.; Stuart, J. D.; Schweiker, S. L.; van Arnold, J.; Bickett, D. M.; Moss, M. L.; Tian, G.; Unwalla, R. J.; Lee, F. W.; Tippin, T. K.; James, M. K.; Grizzle, M. K.; Long, J. E.; Schuster, S. V. J. Med. Chem., 1993, 36, 4313.
7. 5. Frye, S. V.; Haffner, C. D.; Maloney, P. R.; Hiner, R. N.; Dorsey, G. F.; Noe, R. A.; Unwalla, R. J.; Batchelor, K. W.; Bramson, H. N.; Stuart, J. D.; Schweiker, S. L.; van Arnold, J.; Bickett, D. M.; Moss, M. L.; Tian, G.; Lee, F. W.; Tippin, T. K.; James, M. K.; Grizzle, M. K.; Long, J. E.; Groom, D. K. J. Med. Chem. 1995, 38,2621.
8. 6. Rasmusson, S.; Reynolds, G. F.; Utne, T.; Jobson, R. B.; Primka, P. L.; Bergman, C.; Brooks, J. R. J. Med. Chem. 1984, 27, 1690.
9. 7. Lettre, H.; Knof L. Chem. Ber. 1960, 93, 2860.
10. 8. Fang, F. G.; Sharp, M. J. U.S. Patent 5 541 322 , 1996; Chem. Abstr. 1996, 125, 86980.
11. 9. Shoppee, C. W.; Roy, S. K. J. Chem. Soc. 1963, 3775.
12. 10. Ahmad, M. S.; Pillai, N. K.; Chaudhry, Z. H. Aust. J. Chem. 1974, 27, 1537.
13. 11. A Hofmann rearrangement was the obvious choice for introduction of the nitrogen atom due to the well documented use of this reaction in industry. Wallace, E. S.; Lane, J. F. Organic Reactions 1946, Vol III, 267.
14. 12. Fieser, L. F.; Rajagopalan, S. J. Am. Chem. Soc. 1949, 71, 3938.
15. 13. Rosini, G.; Medici, A. Synthesis 1975, 665.
16. 14. Narayanan, C. R.; Parker, M. S.; Wadia, M. S. Tetrahedron Lett. 1970, 54, 4703.
17. 3 see Hugl, H.; Zbiral, E. Tetrahedron 1973, 29, 759.
18. 16. The facial selectivity of the epoxidation was confirmed by X-ray crystallography.
19. 17. Suzuki, M.; Watanabe, A.; Norori, R. J. Am. Chem. Soc. 1980, 102, 2095.
20. 18. An isomeric mixture of vinylogous methyl esters was formed. These isomers could be separated and identified but for the purposes of the synthesis of 2 were carried forward as a mixture which converged at the target molecule.
21. 19. Lazbin, I. M.; Koser, G. F. J. Org. Chem. 1986, 51, 2669.