Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 21, 2013, Pages 6004-6009

  De Lera Ruiz, Manuel ^a   Zheng, Junying ^a   Berlin, Michael Y ^a   McCormick, Kevin D ^a   Aslanian, Robert G ^a   West, Robert ^a   Hwa, Joyce ^a   Lachowicz, Jean ^a   Van Heek, Margaret ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

H3 antagonists; Histamine

Indexed keywords

BETAHISTINE; DIBENZEPIN; HISTAMINE H3 RECEPTOR ANTAGONIST; NNC 381049; NNC 381202; OBECURE; PHENOTHIAZINE DERIVATIVE; POTASSIUM CHANNEL HERG; RIMONABANT; SIBUTRAMINE; TETRAHYDROLIPSTATIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR CHANGE; BINDING AFFINITY; CONTROLLED STUDY; DRUG EFFICACY; NONHUMAN; OBESITY; RAT; RECEPTOR OCCUPANCY; STRUCTURE ACTIVITY RELATION;

RODENTIA;

H3 ANTAGONISTS; HISTAMINE;

ANIMALS; HISTAMINE H3 ANTAGONISTS; HUMANS; MICROSOMES, LIVER; OBESITY; RATS; RECEPTORS, HISTAMINE H3;

EID: 84885172697     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.08.013     Document Type: Article

References (22)

1. A. Peeters, J.J. Barendregt, F. Willekens, J.P. Mackenbach, A. Al Mamun, and L. Bonneux Ann. Intern. Med. 138 2003 24
2. J.C. Halford Appetite 46 2006 6
3. V. Crowley, G. Yeo, and S. O'Rahilly Nat. Rev. Drug Disc. 1 2002 276
4. K. Ookuma, T. Sakata, K. Fukagawa, H. Yoshimatsu, M. Kurokawa, and H. Machidori Brain Res. 628 1993 235
5. N. Orthen-Gambill, and M. Salomon Physiol. Behav. 51 1992 891
6. A.A. Hancock, and M.E. Brune Expert Opin. Invest. Drugs 14 2005 223
7. K. Malmlof, S. Hastrup, B. Schellerup Wulff, B. Hansen, B. Peschke, C. Jeppesen, R. Hohlweg, and K. Rimvall Biochem. Pharmacol. 73 2007 1237
8. M. Berlin, C.W. Boyce, and M. de Lera Ruiz J. Med. Chem. 54 2011 26
9. K. Takahashi, H. Suwa, T. Ishikawa, and H.J. Kotani Clin. Invest. 110 2002 1791
10. J.M. Arrang, M. Garbarg, and T.T. Quach Eur. J. Pharmacol. 111 1985 73
11. A.A. Hancock, Y.L. Bennani, and E.N. Bush Eur. J. Pharmacol. 487 2004 183
12. Hancock, A.A. Diehl, M.S. Fey, T. Abstr. Eur. Histamine Res. Soc. Dusseldorf/Koln Germany 2004, 54.
13. K. Malmlof, V. Golozoubova, B. Peschke, B.S. Wulff, H.H.F. Refsgaard, P.B. Johansen, T. Cremers, and K. Rimvall Obesity 14 2006 2154
14. K. Malmlof, S. Hastrup, B.S. Wulff, B.C. Hansen, B. Peschke, C.B. Jeppesen, R. Hohlweg, and K. Rimvall Biochem. Pharmacol. 73 2007 1237
15. P.C. Ting, J.F. Lee, M.M. Albanese, J. Wu, R. Aslanian, L. Favreau, C. Nardo, W.A. Korfmacher, R.E. West, S.M. Williams, J.C. Anthes, M.A. Rivelli, M.R. Corboz, and J.A. Hey Bioorg. Med. Chem. Lett. 20 2010 5004
16. Q. Zeng, S.B. Rosenblum, Z. Yang, Y. Jiang, K. McCormick, R. Aslanian, L. Duguma, J. Kozlowski, N.-Y. Shih, J. Hey, R.E. West, W. Korfmacher, M. Berlin, and C.W. Boyce Bioorg. Med. Chem. Lett. 2013 preceeding publication
17. K.H. Weber, and D. Helmut Liebigs Ann. Chem. 3 1979 328
18. de Lera Ruiz, M. Berlin, M.Y. Zheng, J. Aslanian, R.G. McCormick, K.D. Zeng, Q. PCT Int. Appl. 2010, WO 2010011653.
19. de Lera Ruiz, M. Berlin, M.Y. Zheng, J. Aslanian, R.G. McCormick, K.D. PCT Int. Appl. 2010, WO 2010011657.
20. The oral pharmacokinetics evaluations were done using the 'cassette-accelerated rapid rat screen' (CARRS) approach (Sprague-Dawley rats dosed with 10 mg/kg of compound in 20% HPBCD) and their oral AUCs were calculated for the 0-6 h intervals. See W.A. Korfmacher, K.A. Cox, K.J. Ng, J. Veals, Y. Hsieh, S. Wainhaus, L. Broske, D. Prelusky, A. Nomeir, and R.E. White Rapid Commun. Mass Spectrom. 15 2001 335
21. H. Mei, W. Korfmacher, and R. Morrison AAPS J. 8 2006 E493
22. + is measured by flame atomic absorbance spectroscopy