2-Phenylspiroindenes: A novel class of selective estrogen receptor modulators (SERMs)

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 3, 2003, Pages 479-483

  Blizzard, Timothy A ^a   Morgan II, Jerry D ^a   Mosley, Ralph T ^a   Birzin, Elizabeth T ^a   Frisch, Katalin ^a   Rohrer, Susan P ^a   Hammond, Milton L ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACOLBIFENE; BAZEDOXIFENE; ESTROGEN RECEPTOR; HORMONE; INDENE DERIVATIVE; PIPENDOXIFENE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR;

ARTICLE; BLOOD CLOTTING DISORDER; CANCER; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; NONHUMAN; RAT;

ALKYLATION; ANIMALS; BOROHYDRIDES; CRYSTALLOGRAPHY, X-RAY; HUMANS; INDENES; INDICATORS AND REAGENTS; RALOXIFENE; RATS; RECEPTORS, ESTROGEN; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037325596     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00985-X     Document Type: Article

References (30)

1. (a) Manson J.E., Martin K.A. N. Engl. J. Med. 345:2001;34 (b) Keating N.L., Cleary P.D., Rossi A.S., Zaslavsky A.M., Ayanian J.Z. Ann. Intern. Med. 130:1999;545 (c) Kooistra T., Emeis J. J. Curr. Opin. Chem. Biol. 3:1999;495.
2. (a) Manson J.E., Martin K.A. N. Engl. J. Med. 345:2001;34 (b) Keating N.L., Cleary P.D., Rossi A.S., Zaslavsky A.M., Ayanian J.Z. Ann. Intern. Med. 130:1999;545 (c) Kooistra T., Emeis J. J. Curr. Opin. Chem. Biol. 3:1999;495.
3. (a) Manson J.E., Martin K.A. N. Engl. J. Med. 345:2001;34 (b) Keating N.L., Cleary P.D., Rossi A.S., Zaslavsky A.M., Ayanian J.Z. Ann. Intern. Med. 130:1999;545 (c) Kooistra T., Emeis J. J. Curr. Opin. Chem. Biol. 3:1999;495.
4. (a) Jordan, C. Sci. Amer. 1998, OCTOBER, 60.
5. (b) Mitlak, B. H.; Cohen, J. J. Drugs 1999, 57, 665.
6. (c) Miller, C. P.; Komm, B. S. In Annual Reports in Medicinal Chemistry, Doherty, A. M., Ed., Academic: San Diego, 2001, Vol. 36, Chapter 15, pp 149-158
7. Park, W. C.; Jordan V. C. Trends Mol. Med. 2002, 8, 82.
8. (a) Jordan C. Sci. Amer. October:1998;60 (b) Mitlak B.H., Cohen J.J. Drugs. 57:1999;665 (c) Miller, C. P.; Komm, B. S. In Annual Reports in Medicinal Chemistry, Doherty, A. M., Ed., Academic: San Diego, 2001, Vol. 36, Chapter 15, pp 149-158 (d) Park W.C., Jordan V.C. Trends Mol. Med. 8:2002;82 (e) Lonard D.M., Smith C.L. Steroids. 67:2002;15.
9. Jordan V.C. Br. J. Pharmacol. 110:1993;507.
10. (a) Jones C.D., Jevnikar M.G., Pike A.J., Peters M.K., Black L.J., Thompson A.R., Falcone J.F., Clemens J.A. J. Med. Chem. 27:1984;1057
11. (b) Griese T.A., Pennington L.D., Sluka J.P., Adrian M.D., Cole H.W., Fuson T.R., Magee D.E., Phillips L., Rowley E.R., Shetler P.K., Short L.L., Venugopalan M., Yang N.N., Sato M., Glasebrook A.L., Bryant H.U. J. Med. Chem. 41:1998;1272
12. (c) Griese T.A., Sluka J.P., Bryant H.U., Cullinan G.J., Glasebrook A.L., Jones C.D., Matsumoto K., Palkowitz A.D., Sato M., Termine J.D., Winter M.A., Yang N.N., Dodge J.A. Proc. Natl. Acad. Sci. U.S.A. 94:1997;14105
13. (d) Sato M., Griese T.A., Dodge J.A., Bryant H.U., Turner C.H. J. Med. Chem. 42:1999;1
14. (e) Delmas P.D., Bjarnson N.H., Mitlak B.H., Ravoux A.C., Shah A.S., Huster W.J., Draper M., Christiansen C. N. Engl. J. Med. 337:1997;1641
15. (f) Brzozowski A.M., Pike A.C.W., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J., Carlquist M. Nature. 389:1997;753.
16. Rosati R.L., Jardine P.D.S., Cameron K.O., Thompson D.D., Ke H.Z., Toler S.M., Brown T.A., Pan L.C., Ebbinghaus C.F., Reinhold A.R., Elliott N.C., Newhouse B.N., Tjoa C.M., Sweetnam P.M., Cole M.J., Arriola M.W., Gauthier J.W., Crawford D.T., Nickerson D.F., Pirie C.M., Qi H., Simmons H.A., Tkalcevic G.T. J. Med. Chem. 41:1998;2928.
17. Levin M., D'Souza N., Castaner J. Drugs Future. 26:2001;841.
18. Labrie F., Labrie C., Belanger A., Simard J., Giguere V., Tremblay A., Tremblay G. J. Ster. Biochem. Mol. Biol. 79:2001;213.
19. (a) Miller C.P., Collini M.D., Tran B.D., Harris H.A., Kharode Y.P., Marzolf J.T., Moran R.A., Henderson R.A., Bender R.H.W., Unwalla R.J., Greenberger L.M., Yardley J.P., Abou-Gharbia M.A., Lyttle C.R., Komm B.S. J. Med. Chem. 44:2001;1654
20. (b) Miller C.P., Harris H.A., Komm B.S. Drugs. 27:2002;117.
21. 1H NMR.
22. Epstein J.W., Brabander H.J., Fanshawe W.J., Hofmann C.M., McKenzie T.C., Safir S.R., Osterberg A.C., Coslich D.B., Lovell F.M. J. Med. Chem. 24:1981;481.
23. Eck G., Julia M., Pfeiffer B., Rolando C. Tetrahedron Lett. 26:1985;4725.
24. Dibromide 27 was prepared by NBS bromination of the TBDPS ether of 3-4,dimethylphenol using the procedure reported for the bromination of 3,4-dimethylanisole: Huang Z., Lakshmikantham M.V., Lyon M., Cava M.P. J. Org. Chem. 65:2000;5413.
25. Lednicer D., Babcock J.C., Marlatt P.E., Lyster S.C., Duncan G.W. J. Med. Chem. 8:1965;52.
26. One of the two isomers was identical to 21 prepared as described in Scheme 3. The structure of the other isomer was confirmed by an NOE experiment.
27. Similar results were obtained when this sequence was applied to the synthesis of 16 and its isomer (corresponding to 33). In this case, the yield of the spiro-alkylation reaction was so low that deprotection of the product was not attempted and the sequence was not completed.
28. Kayaleh N.E., Gupta R.C., Morrissey J.F., Johnson F. Tetrahedron Lett. 38:1997;8121.
29. Argon was used to insure an oxygen-free atmosphere which proved to be critical for this reaction.
30. Seguin H., Gardette D., Moreau M.F., Madelmont J.C., Gramain J.C. Synth. Comm. 28:1998;4257.