Synthesis and SAR of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones as MCH-1 antagonists for the treatment of obesity

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 23, 2010, Pages 7020-7023

  Hadden, Mark ^a   Deering, Dustin M ^a   Henderson, Alan J ^a   Surman, Matthew D ^a   Luche, Michele ^a   Khmelnitsky, Yuri ^a   Vickers, Steven ^b   Viggers, Jean ^b   Cheetham, Sharon ^b   Guzzo, Peter R ^a  

^a ALBANY MOLECULAR RESEARCH INC   (United States)

^b RenaSci Ltd   (United Kingdom)

Author keywords

Antagonist; Indazole; MCH; Obesity; SAR; Suzuki; Weight loss

Indexed keywords

1 (INDAZOL 5 YL)PYRIDIN 2(1H) ONE DERIVATIVE; ANTIOBESITY AGENT; CYTOCHROME P450 2C19; CYTOCHROME P450 3A4; INDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; MESSENGER RNA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG HALF LIFE; DRUG RECEPTOR BINDING; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; MOUSE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; MICE; OBESITY; PYRIDINES; RECEPTORS, PITUITARY HORMONE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149284802     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.037     Document Type: Article

References (14)

1. B.I. Baker Int. Rev. Cytol. 126 1991 1
2. C. Kohler, L. Haglund, and S.W. Swanson J. Comp. Neurol. 223 1984 501
3. H. Vaugham, W.H. Fischer, C. Hoeger, J. Rivier, and W. Vale Endocrinology 125 1989 1660
4. D. Qu, D.S. Ludwing, S. Gammeltoft, M. Piper, M.A. Pelleymounter, M.J. Cullen, W.F. Mathes, J. Przypek, R. Kanarek, and E. Maratos-Flier Nature 380 1996 243
5. M. Shimada, N.A. Tritso, B.B. Lowell, M.S. Flier, and E. Maratos-Flier Nature 396 1998 670
6. D.J. Marsh, D.T. Weingarth, D.E. Novi, D.Y. Chen, M.J. Trumbauer, A.S. Chen, X.M. Guan, M.M. Jiang, Y. Feng, R.E. Camacho, Z. Shen, E.G. Frazier, H. Yu, J.M. Metzger, S.J. Kuca, L.P. Shearman, S. Gopal-Truter, D.J. MacNeil, A.M. Strack, D.E. MacIntyre, L.H.T. Van Der Ploeg, and S. Qian Proc. Natl. Acad. Sci. U.S.A. 99 2002 3240
7. M. Bjursell, A.K. Gerdin, K. Ploj, L. Svensson, L. Svensson, J. Ocarsson, M. Snaith, J. Tornell, and Y. Bohlooly Diabetes 55 2006 725
8. B.J. Sargent, and N.A. Moore Br. J. Clin. Pharmacol. 68 2009 852
9. M.D. McBriar Curr. Opin. Drug Discov. Devel. 9 2006 496
10. D.L. Hertzog, K.A. Al-Barazanji, E.C. Bigham, M.J. Bishop, C.S. Britt, D.L. Carlton, J.P. Cooper, A.J. Daniels, D.M. Garrido, A.S. Goetz, M.K. Grizzle, Y.C. Guo, A.L. Handlon, D.M. Ignar, R.O. Morgan, A.J. Peat, F.X. Tavares, and H. Zhou Bioorg. Med. Chem. Lett. 16 2006 4723
11. M.D. McBriar, H. Guzik, S. Shapiro, J. Paruchova, R. Xu, A. Palani, J.W. Clader, K. Cox, W.J. Greenlee, B.E. Hawes, T.J. Kowalski, K. O'Neil, B.D. Spar, B. Weig, D.J. Weston, C. Farley, and J. Cook J. Med. Chem. 49 2006 2294
12. Sargent, B.; Guzzo, P.; Surman, M.; Freeman, E.; Grabowski, J. F.; Jiang, M.; Jiang, G.; Hadden, M.; Luche, M.; Michels, P.; Khmelnitsky, Y.; Lindsay, J.; Mozhaeva, L.; Zaremba, J.; RenaSci: Viggers, J.; Vickers, S.; Goddard, S.; Cheetham, S.; Comparative pharmacology of AMR-MCH-1 and AMR-MCH-2, MCH-1 receptor antagonists for the treatment of obesity poster presented at the British Pharmacological Society Meeting, Dec 16-18, 2008; Brighton, UK.
13. M.D. Surman, E.F. Freeman, J.F. Grabowski, P.R. Guzzo, M. Hadden, A.J. Henderson, G. Jiang, X. Jiang, M. Luche, Y. Khmelnitsky, S. Vickers, J. Viggers, and S. Cheetham Bioorg. Med. Chem. Lett. 20 2010 7015
14. A.J. Henderson, D.M. Deering, J.F. Grabowski, P.R. Guzzo, M. Hadden, X. Jiang, Y. Khmelnitsky, M. Luche, M.D. Surman, S. Cheetham, S. Vickers, and J. Viggers Bioorg. Med. Chem. Lett. 20 2010 7024