Erratum to "Triazolo-tetrahydrofluorenones as selective estrogen receptor beta agonists" [Bioorg. Med. Chem. Lett. 16 (2006) 4652-4656] (DOI:10.1016/j.bmcl.2006.05.103);Triazolo-tetrahydrofluorenones as selective estrogen receptor beta agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 17, 2006, Pages 4652-4656

  Parker Jr , Dann L ^a   Meng, Dongfang ^a   Ratcliffe, Ronald W ^a   Wilkening, Robert R ^a   Sperbeck, Donald M ^a   Greenlee, Mark L ^a   Colwell, Lawrence F ^a   Lambert, Sherrie ^a   Birzin, Elizabeth T ^a   Frisch, Katalin ^a   Rohrer, Susan P ^a   Nilsson, Stefan ^b   Thorsell, Ann Gerd ^b   Hammond, Milton L ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Karo Bio   (Sweden)

Author keywords

Bioisosteres; ER agonists; SERMs; Tetrahydrofluorenones

Indexed keywords

ESTRADIOL; ESTROGEN RECEPTOR BETA; ESTROGEN RECEPTOR BETA AGONIST; FLUORENONE DERIVATIVE; TRIAZOLE; UNCLASSIFIED DRUG;

AGONIST; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; EMBRYO; HUMAN; HUMAN CELL; NONHUMAN; RAT; RECEPTOR AFFINITY;

EID: 33746380539     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.05.106     Document Type: Erratum

References (31)

1. Stearns V., Ullmer L., Lopez J., Smith Y., Isaacs C., and Hayes D. Lancet 360 (2002) 1851
2. Women's Health Initiative. JAMA 2002, 288, 321.
3. Harris H.A., Katzenellenbogen J.A., and Katzenellenbogen B.S. Endocrinology 143 (2002) 4172
4. Enmark E., Pelto-Huikko M., Grandien K., Lagercrantz S., Fried G., Nordenskjold M., and Gustafsson J.-A. J. Clin. Endocrinol. Metab. 82 (1997) 4258
5. Here is one example:. Kim S., Wu J.Y., Birzin E.T., Frisch K., Chan W., Pai L.Y., Yang Y.T., Mosley R.T., Fitzgerald P.M.D., Sharma N., Dahllund J., Thorsell A.-G., DiNinno F.D., Rohrer S.A., and Hammond M.L. J. Med. Chem. 47 (2004) 2171
6. Meyers M.J., Sun J., Carlson K.E., Marriner G.A., Katzenellenbogen B.S., and Katzenellenbogen J.A. J. Med. Chem. 44 (2001) 4230
7. Schopfer U., Schoeftter P., Bischoff S.F., Nozulak J., Feuerbach D., and Floersheim P. J. Med. Chem. 45 (2002) 1399
8. Henke B.R., Consler T.G., Go N., Hale R.L., Hohman D.R., Jones S.A., Lu A.T., Moore L.B., Moore J.T., Orband-Miller L.A., Robinett R.G., Shearin J., Spearing P.K., Stewart E.L., Turnbull P.S., Weaver S.L., Williams S.P., Wisely G.B., and Lambert M.H. J. Med. Chem. 45 (2002) 5492
9. Yang W., Wang Y., Ma Z., Golla R., Stouch T., Seethala R., Johnson S., Zhou R., Gungor T., Feyen J.H.M., and Dickson J.K. Bioorg. Med. Chem. Lett. 14 (2004) 2327
10. Malamas M.S., Manas E.S., McDevitt R.E., Gunawan I., Xu Z.B., Collini M.D., Miller C.P., Dinh T., Henderson R.A., Keith J.C., and Harris H.A. J. Med. Chem. 47 (2004) 5021
11. Collini M.D., Kaufman D.H., Manas E.S., Harris H.A., Henderson R.A., Xu Z.B., Unwalla R.J., and Miller C.P. Bioorg. Med. Chem. Lett. 14 (2004) 4925
12. Vu A.T., Cohn S.T., Manas E.S., Harris H.A., and Mewshaw R.E. Bioorg. Med. Chem. Lett. 15 (2005) 4520
13. Chesworth R., Wessel M.D., Heyden L., Mangano M., Zawistoski M., Gegnas L., Galluzzo D., Lefker B., Cameron K.O., Tickner J., Lu B., Castleberry T.A., Peterson D.N., Brault A., Perry P., Ng O., Owen T.A., Pan L., Ke H.Z., Brown T.A., Thompson D.D., and DaSilva-Jardine P. Bioorg. Med. Chem. Lett. 15 (2005) 5562
14. Angelis M.D., Stossi F., Waibel M., Katzenellenbogen B.S., and Katzenellenbogen J.A. Bioorg. Med. Chem. 13 (2005) 6529
15. Blizzard T.A., Gude C., Morgan II J.D., Chan W., Birzin E.T., Mojena M., Tudela C., Chen F., Knecht K., Su Q., Kraker B., Mosley R.T., Holmes M.A., Sharma N., Fitzgerald P.M.D., Rohrer S.P., and Hammond M. Bioorg. Med. Chem. Lett. 16 (2006) 834
16. Sun W., Cama L., Birzin E.T., Warrier S., Locco L., Mosley R., Hammond M.L., and Rohrer S.P. Bioorg. Med. Chem. Lett. 16 (2006) 1468
17. Wilkening R.R., Ratcliffe R.W., Tynebor E.C., Wildonger K.J., Fried A.K., Hammond M.L., Mosley R.T., Fitzgerald P.M.D., Sharma N., McKeever B.M., Nilsson S., Carlquist M., Thorsell A., Locco L., Katz R., Frisch K., Birzin E.T., Wilkinson H.A., Mitra S., Cai S., Hayes E.C., Shaeffer J.M., and Rohrer S.P. Bioorg. Med. Chem. Lett. 16 (2006) 3489
18. Wright J.L., Gregory T.F., Kesten S.R., Boxer P.A., Serpa K.A., Meltze L.T., Wise L.D., Espisitia S.A., Konkoy C.S., Whittermore E.R., and Woodward R.M. J. Med. Chem. 43 (2000) 3408-3419
19. Wilkening, R. R.; Ratcliffe, R. W.; Fried, A. K.; Meng, D.; Sun, W.; Colwell, L.; Lambert, S.; Greenlee, M.; Nilsson, S.; Thorsell, A.; Mojena, M.; Tudela, C.; Frisch, K.; Chan, W.; Birzin, E. T.; Rohrer, S. P.; Hammond, M. L. Bioorg. Med. Chem. Lett. in press.
20. Triazoles fused across C6-C7 were inactive. Additionally, C7-C8 imidazoles appear much less promising than the C7-C8 triazoles we now report. D. Parker, R. Wilkening, unpublished results.
21. The nitration gave between 1:1 and 2:1 selectivity for the undesired 6-nitro regioisomer.
22. Chen Q.-Y., and Wu S.-W. J. Chem. Soc., Chem. Commun. (1989) 705 These conditions were modified by the addition of Hunigs base to prevent protecting group removal and subsequent triazole methylation (by methyl iodide which is generated in situ in this reaction)
23. Vedejs E., Haight A.R., and Moss W.O. J. Am. Chem. Soc. 114 (1992) 6556
24. Most often a Chiralcel OJ column was employed using a mixture of EtOH and heptane as the eluent. Compounds (-)-40 and (-)-47 were prepared from (-)-38 (via reprotection and further elaboration).
25. Lemaire M., Guy A., Roussel J., and Guette J.-P. Tetrahedron 43 (1987) 844
26. 2-substituent, often providing no selectivity or increased selectivity for the undesired regioisomer. Unfortunately in several cases the nitration selectivity opposed the bromination selectivity. Future utility of a halo-protection strategy will require a starting material with a pre-installed bromine.
27. 50 values that are reproducible to within a factor of 2-3. Most compounds are single point determinations. For estradiol, the binding data reflect an average of over 100 determinations at 3 h of incubation.
28. Barkhem T., Carlsson B., Nilsson Y., Enmark E., Gustafsson J.-A., and Nilsson S. Mol. Pharmacol. 54 (1998) 105
29. A crystal structure of compound 1 co-crystallized with ERβ supported the configurational assignment of the active enantiomer as S. (see Ref. 17). By analogy we have assigned the more active enantiomer of the triazolo-tetrahydrofluorenones described herein to also be S. The active enantiomer was found to have a negative rotation in each case determined.
30. 2O (2:3:5). Plasma samples were mixed with acetonitrile, centrifuged, and analyzed by LC-MS/MS on an Applied Biosystems MDS SCIEX API tandem mass spectrometer/HPLC system.
31. The difference between the PK of the individual enantiomers of 29 was much more dramatic than we expected based on results for a closely related pyrazole analog (Ref. 19). While many other racemic analogs were examined for rat pharmacokinetics, given the significant difference in the PK profiles for the individual enantiomers, we have not included data for these analogs.