Antiestrogens. 2.1 structure-activity studies in a series of 3-aroy 1-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[6]thien-3-yl][4-[2-(l-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (ly156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity

Journal of Medicinal Chemistry

Volumn 27, Issue 8, 1984, Pages 1057-1066

  Jones, Charles D ^a   Jevnikar, Mary G ^a   Pike, Andrew J ^a   Peters, Mary K ^a   Black, Larry J ^a   Thompson, Allen R ^a   Falcone, Julie F ^a   Clemens, James A ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIESTROGEN; BENZOTHIOPHENE DERIVATIVE; DIMETHYLBENZ[A]ANTHRACENE; ESTRADIOL; ESTRADIOL H 3; NEW DRUG; RADIOISOTOPE; RALOXIFENE; TAMOXIFEN; TAMOXIFEN CITRATE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST; BREAST TUMOR; CANCER CHEMOTHERAPY; CHEMICAL CARCINOGENESIS; DOSE RESPONSE; DRUG ANALYSIS; DRUG ANTAGONISM; DRUG COMPARISON; DRUG IDENTIFICATION; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG SCREENING; DRUG SYNTHESIS; FEMALE GENITAL SYSTEM; LUTEINIZING HORMONE BLOOD LEVEL; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; ORAL DRUG ADMINISTRATION; PHARMACOKINETICS; PROLACTIN BLOOD LEVEL; RAT; STRUCTURE ACTIVITY RELATION; SUBCUTANEOUS DRUG ADMINISTRATION; THERAPY; UTERUS;

9,10-DIMETHYL-1,2-BENZANTHRACENE; ANIMALS; ESTROGEN ANTAGONISTS; FEMALE; MAMMARY NEOPLASMS, EXPERIMENTAL; PIPERIDINES; RALOXIFENE; RATS; RECEPTORS, ESTROGEN; STRUCTURE-ACTIVITY RELATIONSHIP; UTERUS;

EID: 0021201213     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00374a021     Document Type: Article

References (55)

1. C. D. Jones, T. Suarez, E. H. Massey, L. J. Black, and F. C. Tinsley, J. Med. Chem., 22, 962 (1979).
2. R. L. Sutherland and V. C. Jordan, Eds., “Non-Steroidal Antiestrogens”, Academic Press, Sydney, 1981.
3. M. J. K. Harper and A. L. Walpole, Nature (London), 212, 87 (1966).
4. F. P. Palopoli, V. L. Feil, R. E. Allen, D. E. Holtkamp, and A. Richardson, Jr., J. Med. Chem., 10, 84 (1967).
5. M. R. Callantine, R. R. Humphrey, S. L. Lee, B. L. Windsor, M. H. Schottin, and O. P. O'Brien, Endocrinology, 79, 153 (1966).
6. D. Lednicer, J. C. Babcock, S. C. Lyster, and G. W. Duncan, Chem. Ind. (London), 2098 (1961);
7. D. Lednicer, J. C. Babcock, P. E. Marlatt, S. C. Lyster, and G. W. Duncan, J. Med. Chem., 8, 52 (1965).
8. J. K. Landquist and C. J. Marsden, Chem. Ind. (London), 1032 (1966);
9. R. N. Iyer and R. Gopalchari, Ind. J. Chem., 4, 520 (1966).
10. R. R. Crenshaw, A. T. Jeffries, G. M. Luke, L. C. Cheney, and G. Bialy, J. Med. Chem., 14, 1185 (1971).
11. D. Lednicer, J. C. Babcock, S. C. Lyster, and G. W. Duncan, Chem. Ind. (London), 408 (1963);
12. D. Lednicer, S. C. Lyster, and G. W. Duncan, J. Med. Chem., 10, 78 (1967).
13. R. W. J. Carney, W. L, Bencze, J. Wojtkunski, A. A. Renzi, L. Dorfman, and G. de Stevens, J. Med. Chem., 9, 516 (1966);
14. R. Gopalchari and R. N. Iyer, Ind. J. Chem., 4, 331 (1966).
15. H. Mouridsen, T. Palshof, J. Patterson, and L. Battersby, Cancer Treat. Rev., 5, 131 (1978);
16. R. C. Heel, R. N. Brogden, T. M. Speight, and G. S. Avery, Drugs, 16, 1 (1978);
17. B. J. Furr, J. S. Patterson, D. N. Richardson, S. R. Slater, and A. E. Wakeling in “Pharmacological and Biochemical Properties of Drug Substances”, M. E. Goldberg, Ed., American Pharmaceutical Association, Washington, DC, 1979, Vol. 2, pp 335-99.
18. J. H. Click, A. Wein, K. Padavic, W. Negendank, D. Harris, and H. Brodovsky, Cancer Treat. Rep., 64, 813 (1980);
19. J. H. Click, A. Wein, K. Padavic, W. Negendank, D. Harris, and H. Brodovsky, Cancer, 49, 1367 (1982);
20. E. Spremulli, P. DeSimone, and J. Durant, Am. J. Clin. Oncol.-Cancer Clin. Trials, 5, 149 (1982).
21. C. P. Karakousis, R. E. Lopez, H. S. Bhakoo, F. Rosen, R. Mooré, and M. Carlson, Cancer Treat. Rep., 64, 819 (1980);
22. R. Papac, S. Luikhart, and J. Kirkwood, Proc. Am. Assoc. Cancer Res., 21, 358 (1980);
23. M. Al-Sarraf, Proc. Am. Assoc. Cancer Res. ASCO, 20, 378 (1979).
24. P. E. Schwartz, G. Keating, N. MacLusky, F. Naftolin, and A. Eisenfeld, Obstet. Gynecol. (Amsterdam), 59, 583 (1982).
25. K. D. Swenerton, Cancer Treat. Rep., 64, 805 (1980);
26. K. D. Swenerton, D. Shaw, G. W. White, and D. A. Boyes, N. Engl. J. Med., 301, 105 (1979);
27. A. Kauppila and R. Vihko, Acta Obstet. Gynecol. Scand., 60, 589 (1981).
28. E. T. Creagan, J. N. Ingle, D. L. Ahmanns, and S. J. Green, Cancer, 49, 1353 (1982).
29. I. Ricciard and A. Iannirub, Obstet. Gynecol., 54, 80 (1979).
30. A. Klopper and M. Hall, Brit. Med. J., 152 (1971);
31. I. Gerhard and B. Runnebau, Arch. Gynecol., 227, 279 (1979).
32. D. B. Jefferys, Brit. Med. J., 1, 1119 (1979);
33. D. Fairlamb and E. Boesen, Postgrad. Med. J., 53, 269 (1977).
34. F. Comhaire, Int. J. Fé rtil., 21, 232 (1976);
35. K. J. Willis, D. R. London, M. A. Bevis, W. R. Butt, S. S. Lynch, and G. Holder, J. Endocrinol., 73, 171 (1977).
36. L. J. Black in “Hormone Antagonists”, M. K. Agarwal, Ed., Walter deGruyter and Co., New York, 1982, pp 129-45.
37. V. C. Jordan, C. J. Dix, K. E. Naylor, G. Prestwich, and L. Rowsby, J. Toxicol. Environ. Health, 4, 363 (1978).
38. P. Wilkinson, G. Ribeiro, H. Adam, and J. Patterson, Cancer Chemother. Pharmacol., 5, 109 (1980).
39. P. C. Ruenitz, J. R. Bagley, and C. M. Mokler, J. Med. Chem., 25, 1056-60 (1982).
40. D. W. Robertson, J. A. Katzenellenbogen, D. J. Long, E. A. Rorke, and B. S. Katzenellenbogen, J. Steroid. Biochem., 16, 1 (1982).
41. V. K. Winkler, M. A. Nyman, and R. S. Egan, Steroids, 17, 197 (1971).
42. R. N. Iyer and R. Gopalchari, Indian J. Pharm., 31, 49 (1969).
43. A. U. Buzdar, K. C. Powell, S. S. Legha, G. N. Hortobagyi, H. Y. Yap, and G. R. Blumenachein, Proc. Am. Assoc. Cancer Res., 22, 448 (1981).
44. B. T. Pruitt, D. C. Tormey, D. P. Rose, R. S. Witte, and G. Falkson, Clin. Res., 29, 736A (1981).
45. L. J. Black and R. L. Goode, Life Sci., 26, 1453 (1980);
46. L. J. Black, C. D. Jones, and R. L. Goode, Mol. Cell. Endocrinol., 22, 95 (1981).
47. S. Scholl, K. K. Huff, M. E. Lippman, Proceedings of the 63rd Annual Meeting of the Endocrine Society, Abstract No. 175, 1982, p 126.
48. K. Sudo, M. A. Miller, F. J. Monsma, Jr., B. S. Katzenellenbogen, Proceedings of the 63rd Annual Meeting of the Endocrine Society, Abstract No. 57, 1982, p 94.
49. A. N. Kost, V. A. Budylin, E. D. Matveeva, and D. O. Sterligov, Zh. Org. Khim., 6, 1503 (1970).
50. A. H. Blatt, Org. React. 1, 342 (1941).
51. M. Node, K. Nishide, K. Fuji, and E. Fujita, J. Org. Chem., 45, 4275 (1980).
52. L. J. Black, C. D. Jones, J. H. Clark, and J. A. Clemens, “Breast Cancer Research and Treatment”, Martinus Nijhoff: The Hague, Netherlands, Abstract No. 12, 1982, Vol. 2, No. 3, p 279.
53. L. J. Black, C. D. Jones, and J. F. Falcone, Life Sci., 32, 1031 (1983).
54. D. W. Robertson, J. A. Katzenellenbogen, J. R. Hayes, and B. S. Katzenellenbogen, J. Med. Chem., 25, 167 (1982).
55. M. Freund and H. H. Reitz, Chem. Ber., 39, 2235 (1906).