Novel 11β-HSD1 inhibitors: C-1 versus C-2 substitution and effect of the introduction of an oxygen atom in the adamantane scaffold

Bioorganic and Medicinal Chemistry Letters

Volumn 25, Issue 19, 2015, Pages 4250-4253

  Leiva, Rosana ^a   Seira, Constantí ^a   McBride, Andrew ^b   Binnie, Margaret ^b   Luque, F Javier ^a   Bidon Chanal, Axel ^a   Webster, Scott P ^b   Vázquez, Santiago ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

11 HSD1 inhibitors; Adamantane; Drug discovery; Molecular modeling

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1 INHIBITOR; ADAMANTANE; HYDROCARBON; OXIDOREDUCTASE INHIBITOR; OXYGEN; UNCLASSIFIED DRUG; 11BETA HYDROXYSTEROID DEHYDROGENASE 1; ENZYME INHIBITOR;

ARTICLE; ATOM; HUMAN; HYDROGEN BOND; MOLECULAR DYNAMICS; MOLECULAR MODEL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; METABOLISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; ADAMANTANE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OXYGEN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84945441567     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2015.07.097     Document Type: Article

References (43)

1. G. Lamoureux, and G. Artavia Curr. Med. Chem. 17 2010 2967
2. J. Liu, D. Obando, V. Liao, T. Lifa, and R. Codd Eur. J. Med. Chem. 2011 1949 46
3. L. Wanka, K. Iqbal, and P.R. Schreiner Chem. Rev. 113 2013 3516
4. G. Zoidis, N. Kolocouris, G.B. Foscolos, A. Kolocouris, G. Fytas, P. Karayannis, E. Padalko, J. Neyts, and E. DeClercq Antiviral Chem. Chemother. 14 2003 153
5. For another, non-related example, see: W.-G. Lee, S.-D. Lee, J.-H. Cho, Y. Jung, J.-H. Kim, T.T. Hien, K.-W. Kang, H. Ko, and Y.-C. Kim J. Med. Chem. 55 2012 3687
6. J.S. Scott, and J. Chooramun 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) inhibitors in Development R.M. Jones, New Therapeutic Strategies for Type 2 Diabetes Small Molecule Approaches, RSC Drug Discovery Series No. 27 2012 Royal Society of Chemistry Cambridge 109 141
7. L.L. Gathercole, G.G. Lavery, S.A. Morgan, M.S. Cooper, A.J. Sinclair, J.W. Tomlinson, and P.M. Stewart Endocrine Rev. 34 2013 525
8. J.S. Scott, F.W. Goldberg, and A.V. Turnbull J. Med. Chem. 57 2014 4466
9. S. Olson, S.D. Aster, K. Brown, L. Carbin, D.W. Graham, A. Hermanowski-Vosatka, C.B. LeGrand, S.S. Mundt, M.A. Robbins, J.M. Schaeffer, L.H. Slossberg, M.J. Szymonifka, R. Thieringer, S.D. Wright, and J.M. Balkovec Bioorg. Med. Chem. Lett. 15 2005 4359
10. B. Sorensen, J. Rohde, J. Wang, S. Fung, K. Monzon, W. Chiou, L. Pan, X. Deng, D. Stolarik, E.U. Frevert, P. Jacobson, and J.T. Link Bioorg. Med. Chem. Lett. 16 2006 5958
11. C.L. Becker, K.M. Engstrom, F.A. Kerdesky, J.C. Tolle, S.H. Wagaw, and W. Wang Org. Process Res. Dev. 12 2008 1114
12. J.S. Scott, P. Barton, S.N.L. Bennett, J. deSchoolmeester, L. Godfrey, E. Kilgour, R.M. Mayers, M.J. Packer, A. Rees, P. Schofield, N. Selmi, J.G. Swales, and P.R.O. Whittamore Med. Chem. Commun. 3 2012 1263
13. J.S. Scott, J. deSchoolmeester, E. Kilgour, R.M. Mayers, M.J. Packer, D. Hargreaves, S. Gerhardt, D.J. Ogg, A. Rees, N. Selmi, A. Stocker, J.G. Swales, and P.R.O. Whittamore J. Med. Chem. 55 2012 10136
14. O. Venier, C. Pascal, A. Braun, C. Namane, P. Mougenot, O. Crespin, F. Pacquet, C. Mougenot, C. Monseau, B. Onofri, R. Dadji-Faïhun, C. Leger, M. Ben-Hassine, T. Van-Pham, J.-L. Ragot, C. Philippo, G. Farjot, L. Noah, K. Maniani, A. Boutarfa, E. Nicolaï, E. Guillot, M.-P. Pruniaux, S. Güssregen, C. Engel, A.-L. Coutant, B. de Miguel, and A. Castro Bioorg. Med. Chem. Lett. 23 2013 2414
15. S.B. Park, W.H. Jung, N.S. Kang, J.S. Park, G.H. Bae, H.Y. Kim, S.D. Rhee, S.K. Kang, J.H. Ahn, H.G. Jeong, and K.Y. Kim Eur. J. Pharmacol. 721 2013 70
16. S. Okazaki, T. Takahashi, T. Iwamura, J. Nakaki, Y. Sekiya, M. Yagi, H. Kumagai, M. Sato, S. Sakami, A. Nitta, K. Kawai, and M. Kainoh J. Pharmacol. Exp. Ther. 351 2014 181
17. S.Y. Byun, Y.J. Shin, K.Y. Nam, S.P. Hong, and S.K. Ahn Life Sci. 120 2015 1
18. For some examples of 1-substituted adamantane evaluated as 11β-HSD1 inhibitors see: S. Olson, S.D. Aster, K. Brown, L. Carbin, D.W. Graham, A. Hermanowski-Vosatka, C.B. LeGrand, S.S. Mundt, M.A. Robbins, J.M. Schaeffer, L.H. Slossberg, M.J. Szymonifka, R. Thieringer, S.D. Wright, and J.M. Balkovec Bioorg. Med. Chem. Lett. 15 2005 4359
19. X. Su, F. Pradaux-Caggiano, M.P. Thomas, M.W.Y. Szeto, H.A. Halem, M.D. Culler, N. Vicker, and B.V.L. Potter Chem. Med. Chem. 5 2010 1026
20. X. Su, N. Vicker, M.P. Thomas, F. Pradaux-Caggiano, H.A. Halem, M.D. Culler, and B.V.L. Potter Chem. Med. Chem. 6 2011 1439
21. X. Su, F. Pradaux-Caggiano, N. Vicker, M.P. Thomas, H.A. Halem, M.D. Culler, and B.V.L. Potter Chem. Med. Chem. 6 2011 1616
22. H. Wang, J.A. Robl, L.G. Hamann, L. Simpkins, R. Golla, Y.-X. Li, R. Seethala, T. Zvyaga, D.A. Gordon, and J.J. Li Bioorg. Med. Chem. Lett. 21 2011 4146
23. S.H. Kim, S.W. Kwon, S.Y. Chu, J.H. Lee, B. Narsaiah, C.H. Kim, S.K. Kang, N.S. Kang, S.D. Rhee, M.A. Bae, S.H. Ahn, D.C. Ha, K.Y. Kim, and J.H. Ahn Chem. Pharm. Bull. 59 2011 46
24. X. Su, H.A. Halem, M.P. Thomas, C. Moutrille, M.D. Culler, N. Vicker, and B.V.L. Potter Bioorg. Med. Chem. 20 2012 6394
25. For example, the clogP of amide 2 (2.64) is 1 unit lower than that of amide 1 (3.68). Calculated using BioByte software: BioLoom 5.0 BioByte Co., Claremont, CA, USA. http://www.biobyte.com
26. S.P. Webster, P. Ward, M. Binnie, E. Craigie, K.M.M. McConnell, K. Sooy, A. Vinter, J.R. Seckl, and B.R. Walker Bioorg. Med. Chem. Lett. 17 2007 2838
27. G. Xia, L. Liu, H. Liu, J. Yu, Z. Xu, Q. Chen, C. Ma, P. Li, B. Xiong, X. Liu, and J. Shen Chem. Med. Chem. 8 2013 577
28. V.S.C. Yeh, R. Kurukulasuriya, D. Madar, J.R. Patel, S. Fung, K. Monzon, W. Chiou, J. Wang, P. Jacobson, H.L. Sham, and J.T. Link Bioorg. Med. Chem. Lett. 16 2006 5408
29. X.-Y. Ye, S.Y. Chen, A. Nayeem, R. Golla, R. Seethala, M. Wang, T. Harper, B.G. Sleczka, B. He, D.A. Gordon, and J.A. Robl Bioorg. Med. Chem. Lett. 21 2011 6699
30. K.D. Freeman-Cook, R.L. Hoffman, and T.W. Johnson Future Med. Chem. 5 2013 113
31. C.W. Murray, D.A. Erlanson, A.L. Hopkins, G.M. Keseru, P.D. Leeson, D.C. Rees, C.H. Reynolds, and N.J. Richmond J. Med. Chem. 5 2014 616
32. C.M. Tice, W. Zhao, Z. Xu, S.T. Cacatian, R.D. Simpson, Y.-J. Ye, S.B. Singh, B.M. McKeever, P. Lindblom, J. Guo, P.M. Krosky, B.A. Kruk, J. Berbaum, R.K. Harrison, J.J. Johnson, Y. Bukhtiyarov, R. Panemangalore, B.B. Scott, Y. Zhao, J.G. Bruno, L. Zhuang, G.M. McGeehan, W. He, and D.A. Claremon Bioorg. Med. Chem. Lett. 20 2010 881
33. M.D. Duque, P. Camps, L. Profire, S. Montaner, S. Vázquez, F.S. Sureda, J. Mallol, M. López-Querol, L. Naesens, E. De Clercq, S.R. Prathalingam, and J.M. Kelly Bioorg. Med. Chem. 17 2009 3198
34. R. Leiva, S. Gazzarrini, R. Esplugas, A. Moroni, L. Naesens, F.X. Sureda, and S. Vázquez Tetrahedron Lett. 56 2015 1272
35. Urea 6 had been synthesized previously using a Pd-catalyzed carbonylation reaction: K. Orito, M. Miyazawa, T. Nakamura, A. Horibata, H. Ushito, H. Nagasaki, M. Yuguchi, S. Yamashita, T. Yamazaki, and M. Tokuda J. Org. Chem. 71 2006 5951
36. The N-methyl derivative of 8 is reported to be a submicromolar inhibitor of 11β-HSD1. See, S. Richards, B. Sorensen, H. Jae, M. Winn, Y. Chen, J. Wang, S. Fung, K. Monzon, E.U. Frevert, P. Jacobson, H. Sham, and J.T. Link Bioorg. Med. Chem. Lett. 16 2006 6241
37. For further related 2,2-disubstituted adamantanes that led to the discovery of the clinical candidate BMS-816336 see: X.-Y. Ye, D. Yoon, S.Y. Chen, A. Nayeem, R. Golla, R. Seethala, M. Wang, T. Harper, B.G. Sleczka, A. Apedo, Y.-X. Li, B. He, M. Kirby, D.A. Gordon, and J.A. Robl Bioorg. Med. Chem. Lett. 24 2014 654
38. X.-Y. Ye, S.Y. Chen, S. Wu, D.S. Yoon, H. Wang, Z. Hong, S.P. Oconnor, J. Li, J. Li, S. Walker, L.J. Kennedy, A. Apedo, A. Nayeem, S. Sheriff, P. Morin, D. Camac, T. Harrity, R. Zebo, J. Taylor, N. Morgan, R. Ponticiello, R. Golla, R. Seethala, M. Wang, T. Harper, B.G. Sleczka, B. He, M. Kirby, J. DiMarco, R. Scaringe, R.L. Hanson, Z. Guo, J. Li, J.-H. Sun, M.K. Wong, B.-C. Chen, L. Haque, D.K. Leahy, C. Chan, Y.-X. Li, T. Zvyaga, L. Hansen, C. Patel, D.A. Gordon, and J.A. Robl Chem. Abstr. 2015 477592
39. R.A. Friesner, R.B. Murphy, M.P. Repasky, L.L. Frye, J.R. Greenwood, T.A. Halgren, P.C. Sanschagrin, and D.T. Mainz J. Med. Chem. 49 2006 6177
40. H. Cheng, J. Hoffman, P. Le, S.K. Nair, S. Cripps, J. Matthews, C. Smith, M. Yang, S. Kupchinsky, K. Dress, M. Edwards, B. Cole, E. Walters, C. Loh, J. Ermolieff, A. Fanjul, G.B. Bhat, J. Herrera, T. Pauly, N. Hosea, G. Paderes, and P. Rejto Bioorg. Med. Chem. Lett. 20 2010 2897
41. C. Curutchet, M. Orozco, and F.J. Luque J. Comput. Chem. 22 2001 1180
42. M. Kolar, J. Fanfril, M. Lepsik, F. Fort, F.J. Luque, and P. Hobza J. Phys. Chem. B 117 2013 5950
43. G.R. Robb, S. Boyd, C.D. Davies, A.G. Dossetter, F.W. Goldberg, P.D. Kemmitt, J.S. Scott, and J.G. Swales Med. Chem. Commun. 6 2015 926