Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 11, 2005, Pages 2752-2757

  Souers, Andrew J ^a   Gao, Ju ^a   Wodka, Dariusz ^a   Judd, Andrew S ^a   Mulhern, Mathew M ^a   Napier, James J ^a   Brune, Michael E ^a   Bush, Eugene N ^a   Brodjian, Sevan J ^a   Dayton, Brian D ^a   Shapiro, Robin ^a   Hernandez, Lisa E ^a   Marsh, Kennan C ^a   Sham, Hing L ^a   Collins, Christine A ^a   Kym, Philip R ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

MCHR1; Obesity

Indexed keywords

ANTIOBESITY AGENT; DEXFENFLURAMINE; HORMONE RECEPTOR BLOCKING AGENT; INDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE; UREA DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SYNTHESIS; MOUSE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; WEIGHT REDUCTION;

ANIMALS; INDAZOLES; MICE; OBESITY; RECEPTORS, SOMATOSTATIN; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 21144448631     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.03.114     Document Type: Article

References (16)

1. Y. Saito, H.-P. Nothacker, and O. Civelli Trends Endocrinol. Metab. 11 2000 299 303
2. M.W. Schwartz, S.C. Woods, D. Porte Jr., R.J. Selley, and D.G. Baskin Nature 404 2000 661 671
3. D.S. Ludwig, N.A. Tritos, J.W. Mastaitis, R. Kulkarni, E. Kokkotou, J. Elmquist, B. Lowell, J.S. Flier, and E. Maratos-Flier J. Clin. Invest. 107 2001 379 386
4. M. Shimada, N.A. Tritos, B.B. Lowell, J.S. Flier, and E. Maratos-Flier Nature 396 1998 670 674
5. Y. Chen, C. Hu, C.-K. Hsu, Q. Zhang, C. Bi, M. Asnicar, H.M. Hsiung, N. Fox, L.J. Slieker, D.D. Yang, M.L. Heiman, and Y. Shi Endocrinology 143 2002 2469 2477
6. D.J. Marsh, D.T. Weingarth, D.E. Novi, H.Y. Chen, M.E. 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 3245
7. Multiple patents describing small molecule MCHr1 antagonists have been published recently. For excellent reviews on the subject, see the following: T.J. Kowalski, and M.D. McBriar Expert Opin. Invest. Drugs 13 2004 1113 1122
8. A. Browning Expert Opin. Ther. Pat. 14 2004 313 325
9. C.A. Collins, and P.R. Kym Curr. Opin. Invest. Drugs 4 2003 386 394
10. A.J. Souers, J. Gao, M. Brune, E. Bush, D. Wodka, A. Vasudevan, A. Judd, M. Mulhern, S. Brodjian, B. Dayton, R. Shapiro, L.E. Hernandez, K.C. Marsh, H.L. Sham, C.A. Collins, and P.R. Kym J. Med. Chem. 2005 ASAP
11. Similar results were obtained in the previous study (Ref. 8), as 5-substituted indazoles consistently showed better oral exposure than 6-substituted indazoles
12. M.J. Bickerdike Curr. Top. Med. Chem. 3 2003 885 897
13. K. Sjogren, N. Hellberg, Y.M. Bohlooly, L. Savendahl, M.S. Johansson, T. Berglindh, I. Bosaeus, and C. Ohlsson J. Nutr. 131 2001 2963 2966
14. B. Borowsky, M.M. Durkin, K. Ogozalek, M.R. Marzabadi, J. DeLeon, B. Lagu, R. Heurich, H. Lichtblau, Z. Shaposhnik, I. Daniewska, T.P. Blackburn, T.A. Branchek, C. Gerald, P.J. Vaysse, and C. Forray Nature Med. 8 2002 779 781
15. S. Takekawa, A. Asami, Y. Ishihara, J. Terauchi, K. Kato, Y. Shimomura, M. Mori, H. Murakoshi, K. Kato, N. Suzuki, O. Nishimura, and M. Fujino Eur. J. Pharmacol. 438 2002 129 135
16. Handlon, A. L.; Al-Barazanji, A.; Barvian, K. K.; Bigham, E. C.; Carlton, D. L.; Carpenter, A. J.; Cooper, J. P.; Daniels, A. J.; Garrison, D. T.; Goetz, A. S.; Green, G. M.; Grizzle, M. K.; Guo, Y. C.; Hertzog, D. L.; Hyman, C. E.; Ignar, D. M.; Peckham, G. E.; Speake, J. D.; Britt, C.; Swain, W. R. Abstracts of Papers, 228th National Meeting of the American Chemical Society; American Chemical Society: Washington, DC, 2004; p 193