Synthesis and activity of a new class of pathway-selective estrogen receptor ligands: Hydroxybenzoyl-3,4-dihydroquinoxalin-2(1H)-ones

Bioorganic and Medicinal Chemistry

Volumn 14, Issue 10, 2006, Pages 3455-3466

  Mahaney, Paige E ^a   Webb, Michael B ^a   Ye, Fei ^a   Sabatucci, Joseph P ^a   Steffan, Robert J ^a   Chadwick, Christopher C ^a   Harnish, Douglas C ^a   Trybulski, Eugene J ^a  

^a PFIZER INC   (United States)

Author keywords

Anti inflammatory activity; Estrogen receptor ligands; Hydroxybenzoyl 3,4 dihydroquinoxalin 2(1H) ones; NF B

Indexed keywords

1 ALKYL 4 (4 HYDROXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1 ALLYL 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1 ALLYL 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1 BUTYL 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1 BUTYL 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1 CYCLOPENTYL 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1,3 DIETHYL 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 1,3 DIETHYL 7 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 METHYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 1 ISOBUTYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 1 ISOPROPYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 1 METHYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 1 PENTYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 HYDROXYBENZOYL) 1 PROPYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 (4 METHOXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 ETHYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 ISOPROPYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 METHYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 6 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 PROPYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 7 FLUORO 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 7 FLUORO 4 (4 METHOXYBENZOYL) 3,4 DIHYDROQUINOXALIN 2(1H) ONE; 3 ETHYL 7 FLUORO 4 [(4 HYDROXYPHENYL)SULFONYL] 1 METHYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; ESTROGEN; ESTROGEN RECEPTOR; ETHYL 4 [[2 ETHYL 6 FLUORO 3 OXO 3,4 DIHYDROQUINOXALIN 1(2H) YL]SULFONYL]PHENYLCARBONATE; ETHYL 4 [[2 ETHYL 7 FLUORO 3 OXO 3,4 DIHYDROQUINOXALIN 1(2H) YL]SULFONYL]PHENYLCARBONATE; HYDROXYBENZOYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; METHOXYBENZOYL 3,4 DIHYDROQUINOXALIN 2(1H) ONE; QUINOLONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG SYNTHESIS; ESTROGEN ACTIVITY;

CELLS, CULTURED; DRUG EVALUATION, PRECLINICAL; HUMANS; LIGANDS; MOLECULAR STRUCTURE; NF-KAPPA B; QUINOXALINES; RECEPTORS, ESTROGEN; SIGNAL TRANSDUCTION;

EID: 33645870720     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2006.01.001     Document Type: Article

References (19)

1. Tak P.P., and Firestein G.S. J. Clin. Invest. 107 (2001) 7-11
2. Evans M.J., Harris H.A., Miller C.P., Karathanasis S.K., and Adelman S.J. Endocrinology 143 (2002) 3785-3795
3. Tyree C.M., Zou A., and Allegretto E.A. J. Steroid Biochem. Mol. Biol. 80 (2002) 291-297
4. Mukherjee T.K., Nathan L., Dinh H., Reddy S.T., and Chaudhuri G. J. Biol. Chem. 278 (2003) 11746-11752
5. Caulin-Glaser T., Watson C.A., Pardi R., and Bender J.R. J. Clin. Invest. 98 (1996) 36-42
6. Evans M.J., Lai K., Shaw L.J., Harnish D.C., and Chadwick C.C. Endocrinology 143 (2002) 2559-2570
7. Hodgin J.B., and Maeda N. Endocrinology 143 (2002) 4495-4501
8. Harnish D.C., Albert L.M., Leathurby Y., Eckert A.M., Ciarletta A., Kasaian M., and Keith Jr. J.C. Am. J. Physiol. 286 (2004) G118-G125
9. Tyree C.M., Zou A., and Allegretto E.A. J. Steroid Biochem. Mol. Biol. 80 (2002) 291-297
10. Valentine J.E., Kalkhoven E., White R., Hoare S., and Parker M.G. J. Biol. Chem. 275 (2000) 25322-25329
11. Chadwick C.C., Chippari S., Matelan E., Borges-Marcucci L., Eckert A.M., Keith Jr. J.C., Albert L.M., Leathurby Y., Harris H.A., Bhat R.A., Ashwell M., Trybulski E.J., Winneker R.C., Adelman S.J., Steffan R.J., and Harnish D.C. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 2543-2548
12. Selectivity over ERβ for this compound series was not determined.
13. Thomas T.N., Rhodin J.A., Clark L., Garces A., and Bryant M. Inflamm. Res. 52 (2003) 452-460
14. Steffan R.J., Matelan E., Ashwell M.A., Moore W.J., Solvibile W.R., Trybulski E.J., Chadwick C.C., Chippari S., Kinney T., Eckert A., Borges-Marcucci L., Keith J.C., Xu Z., Mosyak L., and Harnish D.C. J. Med. Chem. 47 (2004) 6435-6438
15. Caggiano, T. J.; Brazzale, A.; Ho, D. M.; Kraml, C. M.; Trybulski, E. J.; Chadwick, C. C.; Chappari, S.; Borges-Marcucci, L.; Eckert, A.; Keith, J. C.; Kenney, T.; Harnish, D. C. J. Med. Chem., submitted for publication.
16. Sabatucci J.P., Ashwell M.A., Trybulski E.J., O'Donnell M.-M., Moore W.J., Harnish D.C., and Chadwick C.C. Bioorg. Med. Chem. Lett. 16 (2006) 854-858
17. Molinari, A. J.; Ashwell, M. A.; Ridgeway, B. H.; Failli, A. A.; Moore, W. J. PCT Int. Appl. WO 2004050631.
18. Brooks P.R., Wirtz M.C., Vetelino M.G., Rescek D.M., Woodworth G.F., Bradley P.M., and Coe J.W. J. Org. Chem. 64 (1999) 9719-9721
19. 3CN/water with 10 mM ammonium acetate) over 4 min at a rate of 0.8 mL/min.