5-(Pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl)indazoles as MCH-1 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 23, 2010, Pages 7015-7019

  Surman, Matthew D ^a   Freeman, Emily E ^a   Grabowski, James F ^a   Hadden, Mark ^a   Henderson, Alan J ^a   Jiang, Guowei ^a   Jiang, Xiaowu ^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

Indazoles; MCH 1 antagonists; Melanin concentrating hormone; Obesity

Indexed keywords

5 (FUROPYRIDINON 5 YL)INDAZOLE; 5 (PYRIDINON 1 YL)INDAZOLE; ANTIOBESITY AGENT; CYTOCHROME P450 3A4; INDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; POTASSIUM CHANNEL HERG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARDIOVASCULAR RISK; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; MOUSE; NONHUMAN; OBESITY; PATCH CLAMP; RISK ASSESSMENT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; CARDIOVASCULAR DISEASES; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; INDAZOLES; MICE; OBESITY; RECEPTORS, PITUITARY HORMONE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149279928     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.039     Document Type: Article

References (20)

1. P. Abelson, and D. Kennedy Science 304 2004 1413
2. C.L. Ogden, M.D. Carroll, L.R. Curtin, M.A. McDowell, C.J. Tabak, and K.M. Flegal J. Am. Med. Assoc. 295 2006 5249
3. G.A. Colditz, W.C. Willett, A. Rotnitzky, and J.E. Manson Ann. Int. Med. 122 1995 481
4. J.P. Després Balliere's Clin. Endocrinol. Metab. 8 1994 629
5. I.S. Okosun, K.M.D. Chandra, S. Choi, J. Christman, G.E.A. Dever, and T.E. Prewitt Obes. Res. 9 2001 1
6. H. Yatsuka, A.R. Folsom, K. Yamagishi, K.E. North, F.L. Brancati, and J. Stevens Stroke 4 2010 417
7. G.A. Bray, and T. Bellanger Endocrine 29 2006 109
8. C.D. Sjostrom, L. Lissner, and L. Sjostrom Obes. Res. 5 1997 519
9. J.C. Seidell, W.M. Verschuren, E.M. Van-Leer, and D. Kromhout Arch. Int. Med. 156 1996 958
10. M.D. McBriar Curr. Opin. Drug Discovery Dev. 9 2006 496
11. J.L. Mendez-Andino, and J.A. Wos Drug Discovery Today 12 2007 972
12. H.J. Dyke, and N.C. Ray Expert Opin. Ther. Patents 12 2002 1639
13. L.L. Rokosz, and D.W. Hobbs Drug News Perspect. 19 2006 273
14. K.W. Hunt, D.A. Moreno, N. Suiter, C.T. Clark, and G. Kim Org. Lett. 11 2009 5054
15. M. Chini, P. Crotti, and F. Macchia Tetrahedron Lett. 31 1990 4661
16. S.A. Hitchcock, and L.D. Pennington J. Med. Chem. 49 2006 7559
17. A. Koreňova, A. Krutosikova, J. Kovac, and S. Celec Collect. Czech. Chem. Commun. 52 1997 192
18. McBriar et al. demonstrated the need for robust brain exposure (>70% ex vivo MCH-1 receptor occupancy) at 6 h post dose to elicit in vivo efficacy. Using this observation as a guide, brain levels were measured at 6 h post dose. M.D. McBriar, H. Guzik, R. Xu, J. Paruchova, S. Li, A. Palani, J.W. Clader, W.J. Greenlee, B.E. Hawes, T.J. Kowalski, K. O'Neill, B. Spar, and B. Weig J. Med. Chem. 48 2005 2274
19. M. Hadden, D.M. Deering, A.J. Henderson, P.R. Guzzo, M.D. Surman, M. Luche, Y. Khmelnitsky, S. Vickers, J. Viggers, and S. Cheetham Bioorg. Med. Chem. Lett. 20 2010 7020
20. 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