Tetrahydrocarboline analogs as MCH-1 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 23, 2010, Pages 7024-7028

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

^a ALBANY MOLECULAR RESEARCH INC   (United States)

^b RenaSci Ltd   (United Kingdom)

Author keywords

MCH; MCH 1; Melanin concentrating hormone; Obesity; Tetrahydrocarboline

Indexed keywords

5 (PYRIDININ 1 YL)INDAZOLE; ANTIOBESITY AGENT; BETA TETRAHYDROCARBOLINE; GAMMA TETRAHYDROCARBOLINE; INDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; TETRAHYDROCARBOLINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; MOUSE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; BODY WEIGHT; CARBOLINES; MICE; OBESITY; RECEPTORS, PITUITARY HORMONE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149282047     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.122     Document Type: Article

References (16)

1. H. Kawauchi, I. Kawazoe, M. Tsubokawa, M. Kishida, and B.I. Baker Nature 305 1983 321
2. A.J. Carpenter, and D.L. Hertzog Expert Opin. Ther. Patents 12 2002 1639
3. G. Skofitsch, D.M. Jacobowitz, and N. Zamir Brain Res. Bull. 15 1985 635
4. J.C. Bittencourt, F. Presse, C. Arias, C. Peto, J. Vaughan, J.L. Nahon, W. Vale, and P.E. Sawchenko J. Comp. Neurol. 319 1992 218
5. C. Kohler, L. Haglund, and S.W.J. Swanson Comp. Neurol. 223 1984 501
6. H. Vaugham, W.H. Fischer, C. Hoeger, J. Rivier, and W. Vale Endocrinology 125 1989 1660
7. 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
8. M.D. McBriar Curr. Opin. Drug Disc. Dev. 9 2006 496
9. B.I. Baker Int. Rev. Cytol. 126 1991 1
10. M.D. Surman, E.F. Freeman, J.F. Grabowski, M. Hadden, A.J. Henderson, G. Jiang, X. Jiang, M. Luche, Y. Khmelnitsky, S. Vickers, J. Viggers, S. Cheetham, and P.R. Guzzo Bioorg. Med. Chem. Lett. 20 2010 7015
11. Devadas, B.; Walker, J.; Selness, S. R.; Boehm, T. L.; Durley, R. C.; Devraj, R.; Hickory, B. S.; Rucker, P. V.; Jerome, K. D.; Madsen, H. M.; Alvira, E.; Promo, M. A.; Blevis-Bal, R. M.; Marrufo, L. D.; Hitchcock, J., Owen, T.; Niang, W.; Li, X.; Shieh, H. S.; Sambandam, A.; Liu, S.; Scott, I. L.; McGee, K. F. PCT/US2004/026193, 2004.
12. K.L. Rinehart, J. Kobayashi, G.C. Harbour, J. Gilmore, M. Mascal, T.G. Holt, L.S. Shield, and F. Lafargue J. Am. Chem. Soc. 109 1987 3378
13. Topai, A.; Rossano, E. C.; Rech, F.; Breccia, P.; Cerbara, I.; Marini, S.; Coletta, M. PCT/WO2008/148617, 2008.
14. M. Hadden, D.M. Deering, A.J. Henderson, M.D. Surman, M. Luche, Y. Khmelnitsky, S. Vickers, J. Viggers, S. Cheetham, and P.R. Guzzo Bioorg. Med. Chem. Lett. 20 2010 7020
15. 3H]- labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro-3- (trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea.
16. 80 concentration.