Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3)

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 5, 2011, Pages 1464-1468

  Adeniji, Adegoke O ^a   Twenter, Barry M ^a   Byrns, Michael C ^a   Jin, Yi ^a   Winkler, Jeffrey D ^a   Penning, Trevor M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Aldo keto reductase (AKR); Androgen biosynthesis; Castrate resistant prostate cancer (CRPC); N Phenylanthranilic acids; Non steroidal anti inflammatory drugs (NSAIDs)

Indexed keywords

3 (PHENYLAMINO)BENZOIC ACID DERIVATIVE; AMINE; BENZOIC ACID DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; OXIDOREDUCTASE INHIBITOR; TESTOSTERONE 17BETA DEHYDROGENASE; UNCLASSIFIED DRUG;

ANDROGEN METABOLISM; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; IC 50; PKA; PROSTATE CANCER; SUBSTITUTION REACTION;

3-HYDROXYSTEROID DEHYDROGENASES; ANILINE COMPOUNDS; BENZOIC ACID; DRUG DISCOVERY; HYDROXYPROSTAGLANDIN DEHYDROGENASES; INHIBITORY CONCENTRATION 50; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE;

EID: 79951726954     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.010     Document Type: Article

References (43)

1. A. Jemal, R. Siegel, J. Xu, and E. Ward CA Cancer J. Clin. 60 2010 277
2. Altekruse, S.F.; Krapcho, M.; Neyman, N.; Aminou, R.; Waldron, W.; Ruhl, J.; Howlader, N.; Tatalovich, Z.; Cho, H.; Mariotto, A.; Eisner, M.P.; Lewis, D.R.; Cronin, K.; Chen, H.S.; Feuer, E.J.; Stinchcomb, D.G.; Edwards, B.K., Eds.; SEER Cancer Statistics Review, 1975-2007; National Cancer Institute: Bethesda, MD, 2010.
3. K.E. Knudsen, and H.I. Scher Clin. Cancer Res. 15 2009 4792
4. K.E. Knudsen, and T.M. Penning Trends Endocrinol. Metab. 21 2010 315
5. J.A. Locke, E.S. Guns, A.A. Lubik, H.H. Adomat, S.C. Hendy, C.A. Wood, S.L. Ettinger, M.E. Gleave, and C.C. Nelson Cancer Res. 68 2008 6407
6. A. O'Donnell, I. Judson, M. Dowsett, F. Raynaud, D. Dearnaley, M. Mason, S. Harland, A. Robbins, G. Halbert, B. Nutley, and M. Jarman Br. J. Cancer 90 2004 2317
7. A.H. Reid, G. Attard, D.C. Danila, N.B. Oommen, D. Olmos, P.C. Fong, L.R. Molife, J. Hunt, C. Messiou, C. Parker, D. Dearnaley, J.F. Swennenhuis, L.W. Terstappen, G. Lee, T. Kheoh, A. Molina, C.J. Ryan, E. Small, H.I. Scher, and J.S. de Bono J. Clin. Oncol. 28 2010 1489
8. G. Attard, A.H. Reid, R. A'Hern, C. Parker, N.B. Oommen, E. Folkerd, C. Messiou, L.R. Molife, G. Maier, E. Thompson, D. Olmos, R. Sinha, G. Lee, M. Dowsett, S.B. Kaye, D. Dearnaley, T. Kheoh, A. Molina, and J.S. de Bono J. Clin. Oncol. 27 2009 3742
9. M.A. Titus, M.J. Schell, F.B. Lih, K.B. Tomer, and J.L. Mohler Clin. Cancer Res. 11 2005 4653
10. R.B. Montgomery, E.A. Mostaghel, R. Vessella, D.L. Hess, T.F. Kalhorn, C.S. Higano, L.D. True, and P.S. Nelson Cancer Res. 68 2008 4447
11. M. Stanbrough, G.J. Bubley, K. Ross, T.R. Golub, M.A. Rubin, T.M. Penning, P.G. Febbo, and S.P. Balk Cancer Res. 66 2006 2815
12. J. Hofland, W.M. van Weerden, N.F. Dits, J. Steenbergen, G.J. van Leenders, G. Jenster, F.H. Schroder, and F.H. de Jong Cancer Res. 70 2010 1256
13. K.M. Fung, E.N. Samara, C. Wong, A. Metwalli, R. Krlin, B. Bane, C.Z. Liu, J.T. Yang, J.V. Pitha, D.J. Culkin, B.P. Kropp, T.M. Penning, and H.K. Lin Endocr. Relat. Cancer 13 2006 169
14. H.K. Lin, J.M. Jez, B.P. Schlegel, D.M. Peehl, J.A. Pachter, and T.M. Penning Mol. Endocrinol. 11 1997 1971
15. D.B. Chen, S.D. Westfall, H.W. Fong, M.S. Roberson, and J.S. Davis Endocrinology 139 1998 3876
16. K. Matsuura, H. Shiraishi, A. Hara, K. Sato, Y. Deyashiki, M. Ninomiya, and S. Sakai J. Biochem. 124 1998 940
17. T. Suzuki-Yamamoto, M. Nishizawa, M. Fukui, E. Okuda-Ashitaka, T. Nakajima, S. Ito, and K. Watanabe FEBS Lett. 462 1999 335
18. J.C. Desmond, J.C. Mountford, M.T. Drayson, E.A. Walker, M. Hewison, J.P. Ride, Q.T. Luong, R.E. Hayden, E.F. Vanin, and C.M. Bunce Cancer Res. 63 2003 505
19. B.M. Forman, P. Tontonoz, J. Chen, R.P. Brun, B.M. Spiegelman, and R.M. Evans Cell 83 1995 803
20. M.E. Burczynski, R.G. Harvey, and T.M. Penning Biochemistry 37 1998 6781
21. T.M. Penning, M.E. Burczynski, J.M. Jez, C.F. Hung, H.K. Lin, H. Ma, M. Moore, N. Palackal, and K. Ratnam Biochem. J. 351 2000 67
22. S. Steckelbroeck, Y. Jin, S. Gopishetty, B. Oyesanmi, and T.M. Penning J. Biol. Chem. 279 2004 10784
23. V. Guerini, D. Sau, E. Scaccianoce, P. Rusmini, P. Ciana, A. Maggi, P.G. Martini, B.S. Katzenellenbogen, L. Martini, M. Motta, and A. Poletti Cancer Res. 65 2005 5445
24. T.M. Penning, and P. Talalay Proc. Natl. Acad. Sci. U.S.A. 80 1983 4504
25. D.R. Bauman, S.I. Rudnick, L.M. Szewczuk, Y. Jin, S. Gopishetty, and T.M. Penning Mol. Pharmacol. 67 2005 60
26. J.G. Lombardino Nonsteroidal Antiinflammatory Drugs 1985 Wiley Interscience New York, NY
27. A.R. Scherrer Antiinflammatory Agents: Chemistry and Pharmacology 1974 Academic Press New York, NY
28. A.L. Lovering, J.P. Ride, C.M. Bunce, J.C. Desmond, S.M. Cummings, and S.A. White Cancer Res. 64 2004 1802
29. M.C. Byrns, Y. Jin, and T.M. Penning JSBMB 2010 10.1016/j.jsbmb.2010.11. 004
30. B.C. Hamann, and J.F. Hartwig J. Am. Soc. 120 1998 3694
31. D.W. Old, J.P. Wolfe, and S.L. Buchwald J. Am. Soc. 120 1998 9722
32. R. Csuk, C. Raschke, and A. Barthel Tetrahedron 60 2004 5737
33. 2 (0.05 equiv) at room temperature. The reaction mixture was allowed to stir at 120 °C for 4-48 h. Once the reaction appeared to be complete by consumption of the bromide (or triflate) by TLC analysis, the mixture was allowed to cool to room temperature, diluted with EtOAc, washed with 2 M aq HCl (2×), brine, and dried over sodium sulfate. The solution was concentrated, loaded on silica gel, and purified by silica gel chromatography. (b) To a solution of methyl ester (1 equiv) in EtOH (0.2 M) was added KOH (2 equiv per ester) in water (0.2 M) at room temperature. The reaction mixture was allowed to stir at 100 °C for 1-6 h. Once the reaction appeared complete by TLC analysis, EtOH was evaporated from the reaction mixture; the resultant solution was cooled to 0 °C and acidified to pH 2 w 2 M aq HCl. The resultant precipitated product was collected by vacuum filtration and washed with water.
34. Y. Jin, S.E. Stayrook, R.H. Albert, N.T. Palackal, T.M. Penning, and M. Lewis Biochemistry 40 2001 10161
35. 50 values were obtained from a single experiment with each concentration run in quadruplicate.
36. N. Koda, Y. Tsutsui, H. Niwa, S. Ito, D.F. Woodward, and K. Watanabe Arch. Biochem. Biophys. 424 2004 128
37. N.J. Davies, R.E. Hayden, P.J. Simpson, J. Birtwistle, K. Mayer, J.P. Ride, and C.M. Bunce Cancer Res. 69 2009 4769
38. B. Stefane, P. Brozic, M. Vehovc, T.L. Rizner, and S. Gobec Eur. J. Med. Chem. 44 2009 2563
39. P. Bydal, V. Luu-The, F. Labrie, and D. Poirier Eur. J. Med. Chem. 44 2009 632
40. W. Qiu, M. Zhou, M. Mazumdar, A. Azzi, D. Ghanmi, V. Luu-The, F. Labrie, and S.X. Lin J. Biol. Chem. 282 2007 8368
41. D. Poirier Curr. Med. Chem. 10 2003 453
42. D. Poirier Expert Opin. Ther. Pat. 20 2010 1123
43. B.S. Selinsky, K. Gupta, C.T. Sharkey, and P.J. Loll Biochemistry 40 2001 5172