Novel histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine scaffold

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 2, 2006, Pages 395-399

  Vaccaro, Wayne D ^a,b   Sher, Rosy ^a   Berlin, Michael ^a   Shih, Neng Yang ^a   Aslanian, Robert ^a   Schwerdt, John H ^a   McCormick, Kevin D ^a   Piwinski, John J ^a   West Jr , Robert E ^a   Anthes, John C ^a   Williams, Shirley M ^a   Wu, Ren Long ^a   She, H Susan ^a   Rivelli, Maria A ^a   Mutter, Jennifer C ^a   Corboz, Michel R ^a   Hey, John A ^a   Favreau, Leonard ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

Author keywords

4 (1H Imidazol 4 yl) methyl piperidine; Allergic rhinitis; Decongestion; H3 antagonists; Histamine; Imidazole series; Norepinephrine

Indexed keywords

AMIDE; ANILINE DERIVATIVE; CARBENE; HISTAMINE H3 RECEPTOR ANTAGONIST; PIPERIDINE DERIVATIVE; 4 (1H IMIDAZOL 4 YLMETHYL)PIPERIDINE; 4-(1H-IMIDAZOL-4-YLMETHYL)PIPERIDINE; ANTIHISTAMINIC AGENT; CYTOCHROME P450 2D6; HISTAMINE H3 RECEPTOR; IMIDAZOLE DERIVATIVE;

ARTICLE; BINDING AFFINITY; DRUG ACTIVITY; DRUG BINDING; DRUG POTENCY; SUBSTITUTION REACTION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; DRUG SCREENING; HUMAN; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

CYTOCHROME P-450 CYP2D6; DRUG EVALUATION, PRECLINICAL; HISTAMINE ANTAGONISTS; HUMANS; IMIDAZOLES; MOLECULAR STRUCTURE; PIPERIDINES; RECEPTORS, HISTAMINE H3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 27944437327     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.09.076     Document Type: Article

References (49)

1. J.M. Arrang, M. Garbarg, and J.C. Schwartz Nature 302 1983 832
2. K. Onodera, A. Yamatodani, T. Watanabe, and H. Wada Prog. Neurobiol. 42 1994 685
3. E. Schlicker, R. Betz, and M. Gothert Arch. Pharmacol. 337 1988 588
4. K. Fink, E. Schliker, A. Neise, and M. Gothert Arch. Pharmacol. 342 1990 513
5. J.P. Trzeciakowski Pharmacol. Exp. Ther. 243 1987 874
6. R.W. Hew, C.R. Hodkinson, and S.J. Hill Br. J. Pharmacol. 101 1990 621
7. G.J. Menkveld, and H. Timmerman Eur. J. Pharmacol. 186 1990 343
8. J. Clapham, and G.J. Kilpatrick J. Pharmacol. 107 1992 919
9. E. Schliker, K. Fink, M. Hinterthaner, and M. Gothert Arch. Pharmacol. 340 1989 633
10. K. Fink, E. Schlicker, and M. Gothert Adv. Biosci. 82 1991 125
11. E. Schlicker, K. Fink, M. Detzner, and M. Gothert J. Neural Transm., Gen. Sect. 93 1993 1
12. J.L. Burgaud, and N. Oudart J. Pharm. Pharmacol. 45 1993 950
13. R. Leurs, R. Bakker, H. Timmerman, and I. de Esch Nat. Rev. Drug Discov. 4 2005 107
14. R. Leurs, P. Blandina, C. Tedford, and H. Timmerman Trends Pharmacol. Sci. 19 1998 177
15. T. Taylor-Clark, R. Sodha, B. Warner, and J. Foreman Br. J. Pharmacol. 144 2005 867
16. R.L. McLeod, R.W Egan, F.M. Cuss, D.C. Bolser, and J.A. Hey T.T. Hansel P.J. Barnes Progress in Respiratory Research Vol. 31 2001 Karger Basel 133
17. R.L. McLeod, G.G. Mingo, C. Herczku, F. DeGennaro-Culver, W. Kreutner, R.W. Egan, and J.A. Hey Am. J. Rhinol. 13 1999 391
18. M. Mor, F. Bordi, C. Silva, S. Rivara, V. Zuliani, F. Vacondio, M. Rivara, E. Barocelli, S. Bertoni, V. Ballabeni, F. Magnanini, M. Impicciatore, and P.V. Plazzi Bioorg. Med. Chem. 12 2004 663 and references therein
19. R. Aslanian, M. Mutahi, N.-Y. Shih, K. McCormick, J. Piwinski, P. Ting, M. Albanese, M. Berlin, X. Zhu, S.-C. Wong, S. Rosenblum, Y. Jiang, R. West, S. She, S. Williams, M. Bryant, and J. Hey Bioorg. Med. Chem. Lett. 12 2002 937
20. C. Dvorak, R. Apodaca, A. Barbier, C. Berridge, S. Wilson, J. Boggs, W. Xiao, T. Lovenberg, and N. Carruthers J. Med. Chem. 48 2005 2229
21. M. Cowart, R. Faghih, M. Curtis, G. Gfesser, Y. Bennani, L. Black, L. Pan, K. Marsh, J. Sullivan, T. Esbenshade, G. Fox, and A. Hancock J. Med. Chem. 48 2005 38
22. B. Peschke, S. Bak, R. Hohlweg, I. Pettersson, H. Refsgaard, D. Viuff, and K. Rimvall Bioorg. Med. Chem. 12 2004 2603
23. F. Zaragoza, H. Stephensen, S. Knudsen, L. Pridal, B. Wulff, and K. Rimvall J. Med. Chem. 47 2004 2833
24. M. Cowart, J. Pratt, A. Stewart, Y. Bennani, T. Esbenshade, and A. Hancock Bioorg. Med. Chem. Lett. 14 2004 689
25. M. Curtis, W. Dwight, J. Pratt, M. Cowart, T. Esbenshade, K. Krueger, G. Fox, J.B. Pan, T. Pagano, A. Hancock, R. Faghih, and Y. Bennani Arch. Pharm. Pharm. Med. Chem. 337 2004 219
26. R. Apodaca, C. Dvorak, W. Xiao, A. Barbier, J. Boggs, S. Wilson, T. Lovenberg, and N. Carruthers J. Med. Chem. 46 2003 3938
27. H. Stark Expert Opin. Ther. Pat. 13 2003 851
28. P. Ting, J. Lee, M. Albanese, W. Tom, D. Solomon, R. Aslanian, N.-Y. Shih, and R. West Bioorg. Med. Chem. Lett. 12 2002 2643
29. H. Stark, K. Purand, A. Hulls, X. Ligneau, M. Garbarg, J.-C. Schwartz, and W. Schunack J. Med. Chem. 39 1996 1220
30. M. Mor, F. Bordi, C. Silva, A. Rivara, P. Crivori, P.V. Plazzi, V. Ballabeni, A. Caretta, E. Barocelli, M. Impiddiatore, P.-A. Carrupt, and B. Testa J. Med. Chem. 40 1997 2571
31. I. De Esch, H. Timmerman, W. Menge, and P. Nederkoorn Arch. Pharm. Pharm. Med. Chem. 333 2000 254
32. I. De Esch, J. Mills, T. Perkins, G. Romeo, M. Hoffmann, K. Wieland, R. Leurs, W. Menge, P. Nederkoorn, P. Dean, and H. Timmerman J. Med. Chem. 44 2001 1666
33. R. Vollinga, J. de Koning, F. Jansen, R. Leurs, W. Menge, and H. Timmerman J. Med. Chem. 37 1994 332
34. R. Turner, S. Ley, and S. Lindell Synlett 1993 1748
35. R. West, A. Zweig, N.-Y. Shih, M. Siegel, R. Egan, and M. Clark Mol. Pharmacol. 38 1990 610
36. R. McLeod, C. Rizzo, R. West, R. Aslanian, K. McCormick, M. Bryant, Y. Hsieh, W. Korfmacher, G. Mingo, L. Varty, S. Williams, N.-Y. Shih, R. Egan, and J. Hey J. Pharmacol. Exp. Ther. 305 2003 1037
37. H. Vandergoot, M. Schepers, G. Sterk, and H. Timmerman Eur. J. Med. Chem. 27 1992 511
38. i values are the average of at least two independent determinations. The assay-to-assay variation was generally ±2-fold.
39. i (gp brain) = 290 nM).
40. M. Murray Drug Metab. Rev. 18 1987 55
41. R. Yang, J. Hey, R. Aslanian, and C. Rizzo Pharmacology 66 2002 128
42. J.R. Halpert, F.P. Guengerich, J.R. Bend, and M.A. Correia Toxicol. Appl. Pharmacol. 125 1994 163
43. B. Testa, and P. Jenner Drug Metab. Rev. 12 1981 1
44. L. Favreau, J. Palamanda, C. Lin, and A. Nomeir Drug Metab. Dispos. 27 1999 436 and references therein
45. T. Shimada, H. Yamazaki, M. Mimura, Y. Inui, and F. Guengerich J. Pharmacol. Exp. Ther. 270 1994 414
46. F. Guengerich J. Pharmacokinet. Biopharm. 24 1996 521
47. J. Lin, and A. Lu Pharmacol. Rev. 49 1997 403
48. A. Verras, I. Kuntz, and P. Ortiz de Montellano J. Med. Chem. 47 2004 3572
49. 3, gp) of 170 and 200 nM, respectively, a 400- to 1000-fold dropoff.