Tetrahydroquinolin-3-yl carbamate glucocorticoid receptor agonists with reduced PEPCK activation

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 6, 2011, Pages 1658-1662

  Roach, Steven L ^a   Higuchi, Robert I ^a   Hudson, Andrew R ^a   Vassar, Angie ^a   Grant, Virginia H S ^a   Lamer, Ryan ^a   Hooper, Charlene ^a   Rungta, Deepa ^a   Syka, Peter M ^a   Mais, Dale E ^a   Marschke, Keith B ^a   Zhi, Lin ^a  

^a LIGAND PHARMACEUTICALS INC   (United States)

Author keywords

Anti inflammatory; Glucocorticoid; PEPCK; SGRM; Tetrahydroquinoline

Indexed keywords

ANTIINFLAMMATORY AGENT; BETAMETHASONE 17ALPHA CARBAMATE DERIVATIVE; DEXAMETHASONE; GLUCOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR AGONIST; HORMONE RECEPTOR STIMULATING AGENT; N BENZYLCARBAMATE; N CYCLOHEXYLCARBAMATE; N ISOPROPYLCARBAMATE; N METHYLCARBAMIC ACID; NONSTEROID ANTIINFLAMMATORY AGENT; PHOSPHOENOLPYRUVATE CARBOXYLASE; PREDNISOLONE; TETRAHYDROQUINOLIN 3 OL; TETRAHYDROQUINOLIN 3 YL CARBAMATE DERIVATIVE; UNCLASSIFIED DRUG;

ADRENAL SUPPRESSION; ARTICLE; ASTHMA; BEHAVIOR CHANGE; BINDING AFFINITY; CHEMICAL REACTION; CONCENTRATION RESPONSE; CORTICOSTEROID INDUCED OSTEOPOROSIS; CROHN DISEASE; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SYNTHESIS; ENZYME ACTIVATION; GLUCONEOGENESIS; GROWTH RETARDATION; HUMAN; HYPERGLYCEMIA; HYPERTENSION; IC 50; INFLAMMATION; LUPUS VULGARIS; MUSCLE ATROPHY; RHEUMATOID ARTHRITIS; SIDE EFFECT; STRUCTURE ACTIVITY RELATION;

CARBOXY-LYASES; ENZYME ACTIVATION; QUINOLINES; RECEPTORS, GLUCOCORTICOID;

EID: 79952360199     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.106     Document Type: Article

References (38)

1. J. Rosen, and J.N. Miner Endocr. Rev. 26 2005 452
2. T. Rhen, and J.A. Cidlowski N. Engl. J. Med. 335 2005 1711
3. H. Schacke, A. Schottelius, W.-D. Docke, P. Strehlke, S. Jaroch, N. Schmees, H. Rehwinkel, H. Hennekes, and K. Asadullah Proc. Natl. Acad. Sci. U.S.A. 101 2004 227
4. H. Schacke, W.D. Docke, and K. Asadullah Pharmacol. Ther. 96 2002 23
5. For reviews on dissociated glucocorticoid receptor agonists see: M. Berlin Expert Opin. Ther. Patents 20 2010 855
6. K. De Bosscher J. Steroid Biochem. Mol. Biol. 120 2010 96
7. A.R. Hudson, S.L. Roach, and R.I. Higuchi Curr. Top. Med. Chem. 8 2008 750
8. H. Schacke, M. Berger, T.G. Hansson, D. McKerrecher, and H. Rehwinkel Expert Opin. Ther. Patents 18 2008 339
9. R.J. Ardecky, A.R. Hudson, D.P. Phillips, J.S. Tyhonas, C. Deckhut, T.L. Lau, Y. Li, E.A. Martinborough, S.L. Roach, R.I. Higuchi, F.J. López, K.B. Marschke, J.N. Miner, D.S. Karanewsky, A. Negro-Vilar, and L. Zhi Bioorg. Med. Chem. Lett. 17 2007 4158
10. A.R. Hudson, S.L. Roach, R.I. Higuchi, D.P. Phillips, R.P. Bissonnette, W.W. Lamph, J. Yen, Y. Li, M.E. Adams, L.J. Valdez, A. Vassar, C. Cuervo, E.A. Kallel, C.J. Gharbaoui, D.E. Mais, J.N. Miner, K.B. Marschke, D. Rungta, A. Negro-Vilar, and L. Zhi J. Med. Chem. 50 2007 4699
11. S.W. Elmore, J.K. Pratt, M.J. Coghlan, Y. Mao, B.E. Green, D.D. Anderson, M.A. Stashko, C.W. Lin, D. Falls, M. Nakane, L. Miller, C.M. Tyree, J.N. Miner, and B. Lane Bioorg. Med. Chem. Lett. 14 2004 1721
12. J.N. Miner, B. Ardecky, K. Benbatoul, K. Griffiths, C.J. Larson, D.E. Mais, K. Marschke, J. Rosen, E. Vajda, L. Zhi, and A. Negro-Vilar Proc. Natl. Acad. Sci. U.S.A. 104 2007 19244
13. S. Jaroch, M. Berger, C. Huwe, K. Krolikiewicz, H. Rehwinkel, H. Schacke, N. Schmees, and W. Skuballa Bioorg. Med. Chem. Lett. 20 2010 5835
14. R.P. Robinson, L. Buckbinder, A.I. Haugeto, P.A. McNiff, M.L. Milham, M.R. Reese, J.F. Schaefer, Y.A. Abramov, J. Bordner, Y.A. Chantigny, E.F. Kleinman, E.R. Laird, B.P. Morgan, J.C. Murray, E.D. Salter, M.D. Wessel, and S.A. Yocum J. Med. Chem. 52 2009 1731
15. H-Y. Xiao, D-R. Wu, M.F. Malley, J.Z. Gougoutas, S.F. Habte, M.D. Cunningham, J.E. Somerville, J.H. Dodd, J.C. Barrish, S.G. Nadler, and T.G.M. Dhar J. Med. Chem. 53 2010 1270
16. B.V. Yang, D.S. Weinstein, L.M. Doweyko, H. Gong, W. Vaccaro, T. Huynh, H.-Y. Xiao, A.M. Doweyko, L. McKay, D.A. Holloway, J.E. Sommerville, S. Habte, M. Cunningham, M. McMahon, R. Townsend, D. Shuster, J.H. Dodd, S.G. Nadler, and J.C. Barrish J. Med. Chem. 53 2010 8241
17. B.V. Yang, W. Vaccaro, A.M. Doweyko, L.M. Doweyko, T. Huynh, D. Tortolani, S.G. Nadler, L. McKay, J. Somerville, D.A. Holloway, S. Habte, D.S. Weinstein, and J.C. Barrish Bioorg. Med. Chem. Lett. 19 2009 2139
18. M. Bai, G. Carr, R.J. DeOrazio, T.D. Friedrich, S. Dobritsa, K. Fitzpatrick, P.R. Guzzo, D.B. Kitchen, M.A. Lynch, D. Peace, M. Sajad, A. Usyatinsky, and M.A. Wolf Bioorg. Med. Chem. Lett. 20 2010 3017
19. N. Shah, and T.S. Scanlan Bioorg. Med. Chem. Lett. 14 2004 5199
20. A. Ali, J.M. Balkovec, M. Greenlee, M.L. Hammond, G. Rouen, G. Taylor, M. Einstein, L. Ge, G. Harris, T.M. Kelly, P. Mazur, S. Pandit, J. Santoro, A. Sitlani, C. Wang, J. Williamson, M.J. Forrest, E. Carballo-Jane, S. Luell, K. Lowitz, and D. Visco Bioorg. Med. Chem. 16 2008 7535
21. C.F. Thompson, N. Quraishi, A. Ali, J.R. Tata, M.L. Hammond, J.M. Balkovec, M. Einstein, L. Ge, G. Harris, T.M. Kelly, P. Mazur, S. Pandit, J. Santoro, A. Sitlani, C. Wang, J. Williamson, D.K. Miller, T.D. Yamin, C.M. Thompson, E.A. O'Neill, D.M. Zaller, M.J. Forrest, E. Carballo-Jane, and S. Luell Bioorg. Med. Chem. Lett. 15 2005 2163
22. A. Ali, C.F. Thompson, J.M. Balkovec, D.W. Graham, M.L. Hammond, N. Quraishi, J.R. Tata, M. Einstein, L. Ge, G. Harris, T.M. Kelly, P. Mazur, S. Pandit, J. Santoro, A. Sitlani, C. Wang, J. Williamson, D.K. Miller, C.M. Thompson, D.M. Zaller, M.J. Forrest, E. Carballo-Jane, and S. Luell J. Med. Chem. 47 2004 2441
23. D. Kuzmich, T. Kirrane, J. Proudfoot, Y. Bekkali, R. Zindell, L. Beck, R. Nelson, C-K. Shih, A.J. Kukulka, Z. Paw, P. Reilly, R. Deleon, M. Cardozo, G. Nabozny, and D. Thomson Bioorg. Med. Chem. Lett. 17 2007 5025
24. J. Regan, T.W. Lee, R.M. Zindell, Y. Bekkali, J. Bentzien, T. Gilmore, A. Hammach, T.M. Kirrane, A.J. Kukulka, D. Kuzmich, R.M. Nelson, J.R. Proudfoot, M. Ralph, J. Pelletier, D. Souza, L. Zuvela-Jelaska, G. Nabozny, and D.S. Thomson J. Med. Chem. 49 2006 7887
25. K. Biggadike, M. Boudjelal, M. Clackers, D.M. Coe, D.A. Demaine, G.W. Hardy, D. Humphreys, G.G.A. Inglis, M.J. Johnston, H.T. Jones, D. House, R. Loiseau, D. Needham, P.A. Skone, I. Uings, G. Veitch, G.G. Weingarten, I.M. McLay, and S.J.F. Macdonald J. Med. Chem. 50 2007 6519
26. M. Barker, M. Clackers, R. Copley, D.A. Demaine, D. Humphreys, G.G.A. Inglis, M.J. Johnston, H.T. Jones, M.V. Haase, D. House, R. Loiseau, L. Nisbet, F. Pacquet, P.A. Skone, S.E. Shanahan, D. Tape, V.M. Vinader, M. Washington, I. Uings, R. Upton, I.M. McLay, and S.J.F. MacDonald J. Med. Chem. 49 2006 4216
27. C.M. Yates, P.J. Brown, E.L. Stewart, C. Patten, R.J.H. Austin, J.A. Holt, J.M. Maglich, D.C. Angell, R.Z. Sasse, S.J. Taylor, I.J. Uings, and R.P. Trump J. Med. Chem. 53 2010 4531
28. K. Biggadike, M. Caivano, M. Clackers, D.M. Coe, G.W. Hardy, D. Humphreys, H.T. Jones, D. House, A. Miles-Williams, P.A. Skone, I. Uings, V. Weller, I.M. McLay, and S.J.F. Macdonald Bioorg. Med. Chem. Lett. 19 2009 4846
29. K. Biggadike, R.K. Bledsoe, D.M. Coe, T.W.J. Cooper, D. House, M.A. Iannone, S.J.F. Macdonald, K.P. Madauss, I.M. McLay, T.J. Shipley, S.J. Taylor, T.B. Tran, I.J. Uings, V. Weller, and S. Williams Proc. Natl. Acad. Sci. U.S.A. 106 2009 18114
30. M. Clackers, D.M. Coe, D.A. Demaine, G.W. Hardy, D. Humphreys, G.G.A. Inglis, M.J. Johnston, H.T. Jones, D. House, R. Loiseau, D.J. Minick, P.A. Skone, I. Uings, I. McLay, and S.J.F. Macdonald Bioorg. Med. Chem. Lett. 17 2007 4737
31. H.A. Barnett, D.M. Coe, T.W.J. Cooper, T.I. Jack, H.T. Jones, S.J.F. Macdonald, I.M. McLay, N. Rayner, R.Z. Sasse, T.J. Shipley, P.A. Skone, G.I. Somers, S. Taylor, I.J. Uings, J.M. Woolven, and G.G. Weingarten Bioorg. Med. Chem. Lett. 19 2009 158
32. S.L. Roach, R.I. Higuchi, M.E. Adams, Y. Liu, D.S. Karanewsky, K.B. Marschke, D.E. Mais, J.N. Miner, and L. Zhi Bioorg. Med. Chem. Lett. 18 2008 3504
33. S.L. Roach, R.I. Higuchi, A.R. Hudson, M.E. Adams, P.M. Syka, D.E. Mais, J.N. Miner, K.B. Marschke, and L. Zhi Bioorg. Med. Chem. Lett. 21 2011 168
34. Hudson, A. R.; Higuchi, R. I.; Roach, S. L.; Adams, M. E.; Syka, P. M.; Vassar, A.; Mais, D. E.; Miner, J. N.; Marschke, K. B.; Zhi, L. Biorg. Med. Chem. Lett. 2011, 21, 1697.
35. E.C. Guido, E.O. Delorme, D.L. Clemm, R.B. Stein, J. Rosen, and J.N. Miner Mol. Endocrinol. 10 1996 1178
36. E. Imai, P-E. Stromstedt, P.G. Quinn, J. Carlstedt-Duke, J-A. Gustafsson, and D.K. Granner Mol. Cell. Biol. 10 1990 4172
37. H.-J. Thiesen Immunol. Methods Man. 1 1997 315
38. Unpublished results from our laboratories. General procedure for the synthesis of 3-chloro indole analogs: 4 (1.0 equiv) was reacted with N-chlorosuccinimide (1.05 equiv) in chloroform at 0 °C to provide the resulting 3-chloro indole intermediate which was then subjected to either carbamate synthetic route as depicted in Scheme 1.