Improving the developability profile of pyrrolidine progesterone receptor partial agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 1, 2010, Pages 371-374

  Kallander, Lara S ^a   Washburn, David G ^a   Hoang, Tram H ^a   Frazee, James S ^a   Stoy, Patrick ^a   Johnson, Latisha ^a   Lu, Qing ^a   Hammond, Marlys ^a   Barton, Linda S ^a   Patterson, Jaclyn R ^a   Azzarano, Leonard M ^a   Nagilla, Rakesh ^a   Madauss, Kevin P ^a   Williams, Shawn P ^a   Stewart, Eugene L ^a   Duraiswami, Chaya ^a   Grygielko, Eugene T ^a   Xu, Xiaoping ^a   Laping, Nicholas J ^a   Bray, Jeffrey D ^a   Thompson, Scott K ^a   more..

^a GLAXOSMITHKLINE   (United States)

Author keywords

Endometriosis; hERG; Partial agonist; Progesterone; Progesterone receptor; Pyrrolidine; Rat DMPK; Rat OVX model

Indexed keywords

AMIDE; CARBAMIC ACID; MEDROXYPROGESTERONE ACETATE; PROGESTERONE RECEPTOR; PYRROLIDINE DERIVATIVE; SULFONAMIDE;

ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ENDOMETRIOSIS; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; UTERUS WEIGHT;

ANIMALS; BINDING SITES; CARBAMATES; CRYSTALLOGRAPHY, X-RAY; ENDOMETRIOSIS; ETHER-A-GO-GO POTASSIUM CHANNELS; FEMALE; HUMANS; PYRROLIDINES; RATS; RECEPTORS, PROGESTERONE; SULFONAMIDES;

RATTUS;

EID: 72049126967     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.10.092     Document Type: Article

References (18)

1. Mangelsdorf D.J., Thummel C., Beato M., Herrlich P., Schütz G., Umesono K., Blumberg B., Kastner P., Mark M., Chambon P., and Evans R.M. Cell 83 (1995) 835
2. Edgren R.A., and Sturtevant F.M. Am. J. Obstet. Gynecol. 125 (1976) 1029
3. Spitz I.M. Exp. Rev. Obstet. Gynecol. 2 (2007) 227
4. Lundeen S.G., Zhang Z., Zhu Y., Carver J.M., and Winneker R.C. J. Steroid Biochem. Mol. Biol. 78 (2001) 137
5. Mihalyi A., Simsa P., Mutinda K.C., Meuleman C., Mwenda J.M., and D'Hooghe T.M. Exp. Opin. Emerg. Drugs 11 (2006) 503
6. Olive D.L., and Pritts E.A. N. Eng. J. Med. 345 (2001) 266
7. Kern J.C., Terefenko E.A., Fensome A., Unwalla R., Wrobel J., Cohen J., Zhu Y., Berrodin T.J., Yudt M.R., Winneker R.C., Zhang Z., and Zhang P. Bioorg. Med. Chem. Lett. 18 (2008) 5015
8. Zhi L., Tegley C.M., Kallel E.A., Marschke K.B., Mais D.E., Gottardis M.M., and Jones T.K. J. Med. Chem. 41 (1998) 291
9. Dols P.P.M.A., Folmer B.J.B., Hamersma H., Kuil C.W., Lucas H., Ollero L., Rewinkel J.B.M., and Hermkens P.H.H. Bioorg. Med. Chem. Lett. 18 (2008) 1461
10. Thompson S.K., Washburn D.G., Frazee J.S., Madauss K.P., Hoang T.H., Lapinski L., Grygielko E.T., Glace L.E., Trizna W., Williams S.P., Duraiswami C., Bray J.D., and Laping N.J. Bioorg. Med. Chem. Lett. 19 (2009) 4777
11. Gleeson M.P. J. Med. Chem. 51 (2008) 817
12. Washburn D.G., Hoang T.H., Frazee J.S., Johnson L., Hammond M., Manns S., Madauss K.P., Williams S.P., Duraiswami C., Tran T.B., Stewart E.L., Grygielko E.T., Glace L.E., Trizna W., Nagilla R., Bray J.D., and Thompson S.K. Bioorg. Med. Chem. Lett. 19 (2009) 4664
13. Williams S.P., and Sigler P.B. Nature (London) 393 (1998) 392
14. Madauss K.P., Deng S.-J., Austin R.J., Lambert M.H., McLay I., Pritchard J., Short S.A., Stewart E.L., Uings I.J., and Williams S.P. J. Med. Chem. 47 (2004) 3381
15. Compound 20's PDB code is 3KBA.
16. Madauss K.P., Grygielko E.T., Deng S.-J., Sulpizio A.C., Stanley T.B., Wu C., Short S.A., Thompson S.K., Stewart E.L., Laping N.J., Williams S.P., and Bray J.D. Mol. Endocrinol. 21 (2007) 1066
17. Zeng H., Lozinskaya I.M., Lin Z., Willette R.N., Brooks D.P., and Xu X. J. Pharmacol. Exp. Ther. 319 (2006) 957
18. +.