Synthesis and evaluation of a new series of 1′-cyclobutyl-6-(4- piperidyloxy)spiro[benzopyran-2,4′-piperidine] derivatives as high affinity and selective histamine-3 receptor (H 3R) antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 6, 2012, Pages 2151-2153

  Dandu, Reddeppa Reddy ^a   Lyons, Jacquelyn A ^a   Raddatz, Rita ^a   Huang, Zeqi ^a   Aimone, Lisa D ^a   Hudkins, Robert L ^a  

^a CEPHALON INC   (United States)

Author keywords

CEP 26401; H 3R antagonists; Histamine 3

Indexed keywords

1' CYCLOBUTYL 6 (4 PIPERIDYLOXY)SPIRO[BENZOPYRAN 2,4' PIPERIDINE] DERIVATIVE; BENZOPYRAN DERIVATIVE; CYTOCHROME P450; HISTAMINE H1 RECEPTOR; HISTAMINE H2 RECEPTOR; HISTAMINE H3 RECEPTOR; HISTAMINE H3 RECEPTOR ANTAGONIST; HISTAMINE H4 RECEPTOR; PIPERIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; LIVER MICROSOME; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BENZOPYRANS; CYTOCHROME P-450 ENZYME SYSTEM; HISTAMINE ANTAGONISTS; HUMANS; INJECTIONS, INTRAVENOUS; MICROSOMES, LIVER; PIPERIDINES; RATS; RECEPTORS, HISTAMINE H3; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 84857913204     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.01.139     Document Type: Article

References (25)

1. For reviews see M. Berlin, C.W. Boyce, and M. De Lera Ruiz J. Med. Chem. 54 2011 26
2. R.E. Brown, D.R. Stevens, and H.L. Haas Prog. Neurobiol. 63 2001 637
3. R. Leurs, R.A. Bakker, H. Timmerman, and I. de Esch J. Nat. Rev. Drug Discov. 4 2005 107
4. M. Wijtmans, R. Leurs, and I. de Esch Expert Opin. Investig Drugs 16 2007 967
5. T.A. Esbenshade, G.B. Fox, and M.D. Cowart Mol. Interv. 6 2006 77
6. T.A. Esbenshade, K.E. Browman, R.S. Bitner, M. Strakhova, M.D. Cowart, and J.D. Brioni Br. J. Pharmacol. 154 2008 1166
7. R.L. Hudkins, and R. Raddatz Ann. Rep. Med. Chem. 42 2007 49
8. R. Raddatz, M. Tao, and R.L. Hudkins Curr. Top. Med. Chem. 10 2010 153
9. J.D. Brioni, T.A. Esbenshade, T.R. Garrison, S.R. Bitner, and M.D. Cowart J. Pharmacol. Exp. Ther. 336 2011 38
10. T.W. Lovenberg, B.L. Roland, S.J. Wilson, X. Jiang, J. Pyati, A. Huvar, M.R. Jackson, and M.G. Erlander Mol. Pharmacol. 55 1999 1101
11. Bacon, E. R.; Bailey, T. R.; Becknell, N. C.; Chatterjee, S.; Dunn, D.; Hostetler, G. A.; Hudkins, R. L.; Josef, K. A.; Knutsen, L.; Tao, M.; Zulli, A. L. US2010273779, 2010.
12. R.L. Hudkins, R. Raddatz, M. Tao, J.R. Mathiasen, L.D. Aimone, N.C. Becknell, C.P. Prouty, L. Knutsen, M. Yazdanian, G. Moachon, M.A. Ator, J.P. Mallamo, M.J. Marino, E.R. Bacon, and M. Williams J. Med. Chem. 54 2011 4781
13. R. Raddatz, R.L. Hudkins, J.R. Mathiasen, J.A. Gruner, D.G. Flood, L.D. Aimone, S. Le, H. Schaffhauser, M. Gasior, D. Bozyczko-Coyne, M.J. Marino, M.A. Ator, E.R. Bacon, J.P. Mallamo, and M. Williams J. Pharmacol. Exp. Ther. 340 2012 124
14. R.L. Hudkins, L.D. Aimone, T.R. Bailey, R.J. Bendesky, R. Dandu, D.D. Dunn, J.A. Gruner, K.A. Josef, Y. Lin, J. Lyons, V.R. Marcy, J.R. Mathiasen, B.G. Sundar, M. Tao, A.L. Zulli, R. Raddatz, and E.R. Bacon Bioorg. Med. Chem. Lett. 21 2011 5493
15. B.G. Sundar, T. Bailey, E. Bacon, L. Aimone, Z. Huang, J. Lyons, R. Raddatz, and R.L. Hudkins Bioorg. Med. Chem. Lett. 21 2011 5543
16. M. Tao, R. Raddatz, L.D. Aimone, and R.L. Hudkins Bioorg. Med. Chem. Lett. 21 2011 6126
17. R. Dandu, J.A. Gruner, J.R. Mathiasen, L.D. Aimone, G.A. Hostetler, C. Benfield, R.J. Bendesky, V.R. Marcy, R. Raddatz, and R.L. Hudkins Bioorg. Med. Chem. Lett. 21 2011 6362
18. N.C. Becknell, J.A. Lyons, L.D. Aimone, J.A. Gruner, J.R. Mathiasen, R. Rita Raddatz, and R.L. Hudkins Bioorg. Med. Chem. Lett. 21 2011 7076
19. R.L. Hudkins, L.D. Aimone, R. Dandu, D. Dunn, J.A. Gruner, Z. Huang, K.A. Josef, J. Lyons, J.R. Mathiasen, M. Tao, A.L. Zulli, and R. Raddatz Bioorg. Med. Chem. Lett. 22 2012 194
20. N.C. Becknell, R. Dandu, J.A. Lyons, L.D. Aimone, R. Raddatz, and R.L. Hudkins Bioorg. Med. Chem. Lett. 22 2012 186
21. L. Yang, G. Morriello, K. Prendergast, K. Cheng, T. Jacks, W.W. Chan, K.D. Schleim, R.G. Smith, and A.A. Patchett Bioorg. Med. Chem. Lett. 8 1998 107
22. Jean-philippe, L.; Chun Sing, L.; Oscar Miguel, M. WO2010094120, 2010.
23. C.A. Dvorak, R. Apodaca, A.J. Barbier, C.W. Berridge, S.J. Wilson, J.D. Boggs, W. Xiao, T.W. Lovenberg, and N.J. Carruthers J. Med. Chem. 48 2005 2229
24. P. Bonaventure, M. Letavic, C. Dugovic, S. Wilson, L. Aluisio, C. Pudiak, B. Lord, C. Mazur, F. Kamme, S. Nishino, N. Carruthers, and T. Lovenberg Biochem. Pharmacol. 73 2007 1084
25. C.A. Dvorak, R. Apodaca, W. Xiao, J.A. Jablonowski, P. Bonaventure, C. Dugovic, J. Shelton, B. Lord, K. Miller, L.K. Dvorak, T.W. Lovenberg, and N.J. Carruthers Euro. J. Med. Chem. 44 2009 4098