A practical synthesis of 3-substituted Δ(3,6(6))-steroids as new potential 5α-reductase inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 15, 1998, Pages 1949-1952

  Tian, Weisheng ^a   Zhu, Zheng ^b   Liao, Qingjiang ^b   Wu, Yikang ^a  

^a SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY   (China)

^b CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

5 Reductase inhibitor; Coupling reaction; Synthesis

Indexed keywords

ANDROSTANOLONE; AZACOSTEROL; AZASTEROID; EPRISTERIDE; FINASTERIDE; STEROID; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR; TESTOSTERONE;

ARTICLE; CHEMICAL REACTION; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; STRUCTURE ANALYSIS;

ENZYME INHIBITORS; STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP; TESTOSTERONE 5-ALPHA-REDUCTASE;

EID: 0032483104     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00339-4     Document Type: Article

References (28)

1. [1] Andersson, S.; Russell, D. W. Proc. Natl. Acad. Sci. U. S. A. 1990, 87, 3640; Jenkins, E. P.; Andersson, S.; Imperato-McGinley, J.; Wilson, J. D.; Russell, D. W. J. Clin. Invest. 1992, 89, 293.
2. [1] Andersson, S.; Russell, D. W. Proc. Natl. Acad. Sci. U. S. A. 1990, 87, 3640; Jenkins, E. P.; Andersson, S.; Imperato-McGinley, J.; Wilson, J. D.; Russell, D. W. J. Clin. Invest. 1992, 89, 293.
3. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am.; 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
4. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
5. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
6. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
7. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
8. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
9. [2] Rasmusson, G. H. Annu. Rep. Med. Cbem. 1986, 22, 179; Geller, J. J. Am. Geriatr. Soc. 1991, 39, 1208; Gormley, G. J. Urol. Clin. North. Am. 1991, 18, 93; Dallob, A. L.; Sadock, N. S.; Unger, W.; Lipert, S.; Geissier, L. A.; Gregoire, S. L.; Nguyen, H. H.; Morre, E.; Tanaka, W. K. J. Clin. Endocrinol. Metab. 1994, 79, 703; Smith, L. S.; Tegler, J. J. Annu. Rep. Med. Chem. 1989, 24, 177; Gadwood, R. C.; Fiedler, V. C. Annu. Rep. Med. Chem. 1989, 24, 187; Brooks, J. R. J. Clin. Endocrinol. Metab. 1989, 10, 491.
10. [3] a), Rasmusson, G. H.; Reynolds, G. F.; Utne, T.; Jobson, R. B.; Primka, R. L.; Berman, C.; Brooks, J. R. J. Med. Chem. 1984, 27, 1690;
11. b), Frye, S. V.; Haffner, C. D.; Maloney, P. R.; Mook, R. A.; Jr., 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.; Gaochoa, T.; 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;
12. c), Guarna, A.; Belle, C.; Machetti, F.; Occhiato, E. G.; Payne, A. H.; Cassiani, C.; Comerci, A.; Danza, G.; Bellis, D.; Dini, S. J. Med. Chem. 1997, 40, 1112;
13. d), Morzycki, J. W.; Lotowski, Z.; Wilczewska, A. Z.; Stuart, J. D. Bioorg. & Med. Chem. Lett. 1996, 4, 1209;
14. e), Metcalf, B. W.; Holt, D. A.; Levy, M. A.; Erb, J. M.; Heaslip, J. I.; Brandt, M.; Oh, H. J. J. Bioorg. Chem. 1989, 17, 372; Holt, D. A.; Levy, M. A.; Oh, H. J.; Heaslip, J. I.; Brandt, M.; Lan-Hargest, H. Y.; Metcalf, B. W. J. Med. Chem. 1990, 33, 943;
15. e), Metcalf, B. W.; Holt, D. A.; Levy, M. A.; Erb, J. M.; Heaslip, J. I.; Brandt, M.; Oh, H. J. J. Bioorg. Chem. 1989, 17, 372; Holt, D. A.; Levy, M. A.; Oh, H. J.; Heaslip, J. I.; Brandt, M.; Lan-Hargest, H. Y.; Metcalf, B. W. J. Med. Chem. 1990, 33, 943;
16. f), Marget, H. H.; Maria, H.; Mann, J. J. Chem. Soc. Perkin Trans. 1. 1993, 2907;
17. g), Fei, X. S.; Tian, W. S.; Chen, Q.Y. Bioorg. & Med. Chem. Lett. 1997, 7, 3113;
18. h), Jones, C. D.; Audia, J. E.; Lawhorn, D. E.; McQuaid, L. A.; Neubauer, B. L.; Pike,A. J.; Pennington, P. A.; Stamm, N. B.; Toomey, R. E.; Hirsch, K. S. J. Med. Chem. 1993, 36, 421;
19. i), Holt, D. A.; Yamashita, D. S.; Konialian-Beck, A. L.; Luengo, J. I.; Abell, A. D.; Bergsma, D. J.; Brandt, M.; Levy, M. A. J. Med. Chem. 1995, 38, 13;
20. j), Abell, A. D.; Brandt, M.; Levy, M. A.; Holt, D. A. Bioorg. & Med. Chem. Lett. 1994, 4, 2327.
21. [4] Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton, E.; Patel, G. F.; Liang, T.; Cascieri, M.A.; Cheung, A. H.; Brooks, J. R.; Berman, C. J. Med. Chem. 1986, 29, 2298.
22. [5] Sabbir, A.; Sophie, D. Bioorg. & Med. Chem. Lett. 1998, 8, 409.
23. [6] Zhu, Z.; Tian, W. S.; Liao, Q. J. Tetrahedron Lett. 1996, 37, 8553.
24. [7] Ritter, K. Synthesis 1993, 735; Cacchi, S. Synthesis 1986, 320.
25. [7] Ritter, K. Synthesis 1993, 735; Cacchi, S. Synthesis 1986, 320.
26. -1, satisfactory elemental analysis were obtained.
27. -1.
28. [10] The assay of inhibitory activities was performed by professor Tu Zeng-Hong of Shanghai Institute of Material Medica, Chinese Academy of Sciences.