Development of progesterone receptor antagonists from 1,2-dihydrochromeno[3,4-f]quinoline agonist pharmacophore

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 12, 2003, Pages 2075-2078

  Zhi, Lin ^a   Ringgenberg, Josef D ^a   Edwards, James P ^a   Tegley, Christopher M ^a   West, Sarah J ^a   Pio, Barbara ^a   Motamedi, Mehrnouch ^a   Jones, Todd K ^a   Marschke, Keith B ^a   Mais, Dale E ^a   Schrader, William T ^a  

^a LIGAND PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGESTAGEN; MIFEPRISTONE; ONAPRISTONE; PROGESTERONE; PROGESTERONE RECEPTOR MODULATOR; QUINOLINE DERIVATIVE; ZK 299;

ANIMAL EXPERIMENT; ARTICLE; BIOASSAY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; FEMALE; NONHUMAN; PHARMACOPHORE; RAT; STRUCTURE ACTIVITY RELATION;

EID: 12444262282     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00256-7     Document Type: Article

References (22)

1. For SAR information of pharmacophore 1 and clinical opportunities of nonsteroidal progestins, see: (a) Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;291 (b) Edwards J.P., West S.J., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;303 (c) Tegley C.M., Zhi L., Marschke K.B., Gottardis M.M., Yang Q., Jones T.K. J. Med. Chem. 41:1998;4354 (d) Zhi L., Tegley C.M., Edwards J.P., West S.J., Marschke K.B., Gottardis M.M., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;3365 (e) Zhi L., Tegley C.M., Marschke K.B., Mais D.E., Jones T.K. J. Med. Chem. 42:1999;1466.
2. For SAR information of pharmacophore 1 and clinical opportunities of nonsteroidal progestins, see: (a) Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;291 (b) Edwards J.P., West S.J., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;303 (c) Tegley C.M., Zhi L., Marschke K.B., Gottardis M.M., Yang Q., Jones T.K. J. Med. Chem. 41:1998;4354 (d) Zhi L., Tegley C.M., Edwards J.P., West S.J., Marschke K.B., Gottardis M.M., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;3365 (e) Zhi L., Tegley C.M., Marschke K.B., Mais D.E., Jones T.K. J. Med. Chem. 42:1999;1466.
3. For SAR information of pharmacophore 1 and clinical opportunities of nonsteroidal progestins, see: (a) Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;291 (b) Edwards J.P., West S.J., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;303 (c) Tegley C.M., Zhi L., Marschke K.B., Gottardis M.M., Yang Q., Jones T.K. J. Med. Chem. 41:1998;4354 (d) Zhi L., Tegley C.M., Edwards J.P., West S.J., Marschke K.B., Gottardis M.M., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;3365 (e) Zhi L., Tegley C.M., Marschke K.B., Mais D.E., Jones T.K. J. Med. Chem. 42:1999;1466.
4. For SAR information of pharmacophore 1 and clinical opportunities of nonsteroidal progestins, see: (a) Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;291 (b) Edwards J.P., West S.J., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;303 (c) Tegley C.M., Zhi L., Marschke K.B., Gottardis M.M., Yang Q., Jones T.K. J. Med. Chem. 41:1998;4354 (d) Zhi L., Tegley C.M., Edwards J.P., West S.J., Marschke K.B., Gottardis M.M., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;3365 (e) Zhi L., Tegley C.M., Marschke K.B., Mais D.E., Jones T.K. J. Med. Chem. 42:1999;1466.
5. For SAR information of pharmacophore 1 and clinical opportunities of nonsteroidal progestins, see: (a) Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;291 (b) Edwards J.P., West S.J., Marschke K.B., Mais D.E., Gottardis M.M., Jones T.K. J. Med. Chem. 41:1998;303 (c) Tegley C.M., Zhi L., Marschke K.B., Gottardis M.M., Yang Q., Jones T.K. J. Med. Chem. 41:1998;4354 (d) Zhi L., Tegley C.M., Edwards J.P., West S.J., Marschke K.B., Gottardis M.M., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;3365 (e) Zhi L., Tegley C.M., Marschke K.B., Mais D.E., Jones T.K. J. Med. Chem. 42:1999;1466.
6. (a) Edwards J.P., Zhi L., Pooley C.L.F., Tegley C.M., West S.J., Wang M.-W., Gottardis M.M., Pathirana C., Schrader W.T., Jones T.K. J. Med. Chem. 41:1998;2779.
7. (b) Zhi, L.; Tegley, C. M.; Pio, B.; Edwards, J. P.; Motamedi, M.; Jones, T. K.; Marschke, K. B.; Mais, D. E.; Risek, B.; Schrader, W. T. J. Med. Chem. 2003, in press.
8. (a) Kloosterboer H.J., Deckers G.H., Schoonen W.G.E.J., Hanssen R.G.J.M., Rose U.M., Verbost P.M., Hsiu J.G., William R.F., Hodgen G.D. Steroids. 65:2000;733.
9. (b) Palmer S., Campen C.A., Allan G.F., Rybczynski P., Haynes-Johnson D., Hutchins A., Kraft P., Kiddoe M., Lai M.-T., Lombardi E., Pedersen P., Hodgen G.D., Combs D.W. J. Steroids Biochem. Mol. Biol. 75:2000;33.
10. Teutsch G., Ojasoo T., Raynaud J.P. J. Steroid Biochem. 35:1988;549.
11. Gray G.W., Hird M., Lacey D., Toyne K.J. J. Chem. Soc., Perkin Trans. 2. 1989;2041.
12. (a) Eisch J.J., Dluzniewski T. J. Org. Chem. 54:1989;1269.
13. (b) Walter H., Sauter H., Winkler T. Helv. Chim. Acta. 75:1992;1274.
14. 6) 7.58 (t, J=1.7 Hz, 1H), 7.45 (d, J=8.5 Hz, 1H), 7.17 (dd, J=9.8 and 2.3 Hz, 1H), 6.71 (d, J=8.5 Hz, 1H), 5.68 (br s, 1H), 5.51 (s, 1H), 5.40 (s, 2H), 2.12 (s, 3H) and 1.26 (s, 6H).
15. For leading references to cotransfection assays and the family of closely related intracellular receptors to which the progesterone receptor belongs, see: (a) McDonnell D.P., Vegeto E., Gleeson M.A.G. Bio/Technology. 11:1993;1256 (b) Rosen J., Day A., Jones T.K., Jones E.T.T., Nadzan A.M., Stein R.B. J. Med. Chem. 38:1995;4855.
16. For leading references to cotransfection assays and the family of closely related intracellular receptors to which the progesterone receptor belongs, see: (a) McDonnell D.P., Vegeto E., Gleeson M.A.G. Bio/Technology. 11:1993;1256 (b) Rosen J., Day A., Jones T.K., Jones E.T.T., Nadzan A.M., Stein R.B. J. Med. Chem. 38:1995;4855.
17. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.
18. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.
19. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.
20. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.
21. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.
22. For the related nonsteroidal hPR antagonist series, see: (a) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461 (b) Hamann L.G., Winn D.T., Pooley C.L.F., Tegley C.M., West S.J., Farmer L.J., Zhi L., Edwards J.P., Marschke K.B., Mais D.E., Goldman M.E., Jones T.K. Bioorg. Med. Chem. Lett. 8:1998;2731 (c) Zhi L., Tegley C.M., Pio B., West S.J., Marschke K.B., Mais D.E., Jones T.K. Bioorg. Med. Chem. Lett. 10:2000;415 (d) Zhang P., Terefenko E.A., Wrobel J., Zhang Z., Zhu Y., Cohen J., Marschke K.B., Mais D.E. Bioorg. Med. Chem. Lett. 11:2001;2747 (e) Zhang P., Terefenko E.A., Fensome A., Zhang Z., Zhu Y., Cohen J., Winneker R., Wrobel J., Yardley J. Bioorg. Med. Chem. Lett. 12:2002;787 (f) Zhang P., Terefenko E.A., Fensome A., Wrobel J., Winneker R., Lundeen S., Marschke K.B., Zhang Z. J. Med. Chem. 45:2002;4379.