Discovery of spirofused piperazine and diazepane amides as selective histamine-3 antagonists with in vivo efficacy in a mouse model of cognition

Journal of Medicinal Chemistry

Volumn 57, Issue 3, 2014, Pages 733-758

  Brown, Dean G ^a   Bernstein, Peter R ^a   Griffin, Andrew ^a   Wesolowski, Steve ^a   Labrecque, Denis ^a   Tremblay, Maxime C ^a   Sylvester, Mark ^a   Mauger, Russell ^a   Edwards, Phillip D ^a   Throner, Scott R ^a   Folmer, James J ^a   Cacciola, Joseph ^a   Scott, Clay ^a   Lazor, Lois A ^a   Pourashraf, Mehrnaz ^a   Santhakumar, Vijayaratnam ^a   Potts, William M ^a   Sydserff, Simon ^a   Giguère, Pascall ^b   Lévesque, Carine ^b   Dasser, Mohammed ^b   Groblewski, Thierry ^a   more..

^a ASTRAZENECA   (United Kingdom)

^b AstraZeneca Montréal ^*  (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; AZETIDINES; CELL MEMBRANE PERMEABILITY; CHO CELLS; COGNITION; CRICETINAE; CRICETULUS; CYCLOPROPANES; DOGS; HISTAMINE H3 ANTAGONISTS; HUMANS; LEARNING; MADIN DARBY CANINE KIDNEY CELLS; MALE; MICE; MICROSOMES, LIVER; MODELS, MOLECULAR; PIPERAZINES; PIPERIDINES; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, HISTAMINE H3; RECOGNITION (PSYCHOLOGY); SPIRO COMPOUNDS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84894065452     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4014828     Document Type: Article

References (46)

1. 3) of histamine receptor Nature 1983, 302, 832-837
2. 3 antagonists for the treatment of cognitive disorders and Alzheimer's disease J. Pharmacol. Exp. Ther. 2011, 336, 38-46
3. 3 receptor antagonist with efficacy in animal models of osteoarthritis and neuropathic pain Eur. J. Pharmacol. 2012, 684, 87-94
4. 3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder CNS Drugs 2012, 26, 421-434
5. 3 receptor antagonist GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain Pain 2008, 138, 61-78
6. Karagiannidis, I.; Dehning, S.; Sandor, P.; Tarnok, Z.; Rizzo, R.; Wolanczyk, T.; Madruga-Garrido, M.; Hebebrand, J.; Nöthen, M. M.; Lehmkuhl, G.; Farkas, L.; Nagy, P.; Symanska, U.; Anastasiou, Z.; Stathias, V.; Androutsos, C.; Tsironi, V.; Koumoula, A.; Barta, C.; Zill, P.; Mir, P.; Müller, N.; Barr, C.; Paschou, P. Support of the histaminergic hypothesis in Tourette syndrome: Association of the histamine decarboxylase gene in a large sample of families J. Med. Genet. 2013, 50, 760-764
7. 3 receptor: An attractive target for the treatment of cognitive disorders Br. J. Pharmacol. 2008, 154, 1166-1181
8. 3 receptor as a novel therapeutic target for cognitive and sleep disorders Pharmacol. Sci. 2004, 25, 618-625
9. 3 receptor antagonist with drug-like properties J. Pharmacol. Exp. Ther. 2005, 313, 165-175
10. 3 receptor antagonist J. Pharmacol. Exp. Ther. 2005, 313, 176-190
11. 3 receptor as a therapeutic drug target for metabolic disorders: Status, challenges, and opportunities Curr. Top. Med. Chem. 2011, 11, 1430-1446
12. 3 receptors reach out for the clinic Drug Discovery Today 2005, 10, 1613-1627
13. 3 antagonists Annu. Rep. Med. Chem. 2007, 42, 49-62
14. Zhou, D.; Gross, J. L.; Adedoyin, A. B.; Aschmies, S. B.; Brennan, J.; Bowlby, M.; Di, L.; Kubek, K.; Platt, B. J.; Wang, Z.; Zhang, G.; Brandon, N.; Comery, T. A.; Robichaud, A. J. 2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin- 1(2 H)-one derivatives as potent and selective histamine-3 receptor antagonists J. Med. Chem. 2012, 55, 2452-2468
15. 3 receptor antagonists with potent cognition enhancing activity J. Med. Chem. 2012, 55, 414-423
16. 3 receptor function and ligands: Recent developments Mini-Rev. Med. Chem. 2013, 13, 47-57
17. 3 receptor ligands making the final push towards the market Expert Opin. Invest. Drugs 2011, 20, 1629-1648
18. 3 receptor. U.S. Patent Appl. 2007/0066821 A1, March 22, 2007.
19. 3 antagonists/inverse agonists Biochem. Pharmacol. 2006, 71, 1103
20. Ritchie, T. J.; MacDonald, S. J. F. The impact of aromatic ring count on compound developability: Are too many aromatic rings a liability in drug design Drug Discovery Today 2009, 14, 1011-1020
21. + channel blockers J. Med. Chem. 2002, 45, 3844-3853
22. 3 receptor antagonists Bioorg. Med. Chem. Lett. 2006, 16, 897-900
23. 3 receptor antagonists based on the natural product conessine Bioorg. Med. Chem. Lett. 2008, 18, 1490-1494
24. 3 receptor antagonists J. Med. Chem. 2008, 51, 5423-5430
25. Lannang, A. M.; Anjum, S.; Tangmouo, J. G.; Krohn, K.; Choudhary, M. I. Conessin isolated from Holarrhena floribunda Acta Crystallogr. 2007, E63, o3980
26. 3 antagonist Br. J. Pharmacol. 2004, 143, 649-661
27. 3 antagonists J. Med. Chem. 2005, 48, 2229-2238
28. Malmlof, K.; Zaragoza, F.; Golozoubova, V.; Refsgaard, H. H. F.; Cremers, T.; Raun, K.; Wulff, B. S.; Johansen, P. B.; Westerink, B.; Rimvall, K. Influence of a selective histamine receptor antagonist on hypothalamic neural activity, food intake, and body weight Int. J. Obes. 2005, 29, 1402-1412
29. 3 receptor antagonists GSK207040 and GSK 334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats Biochem. Pharmacol. 2007, 73, 1182-1194
30. 3 receptor antagonists: Identification of candidates for clinical development Bioorg. Med. Chem. Lett. 2010, 20, 4210-4214
31. 3 receptor antagonist, reduces the abuse-related effects of alcohol in rats Psychopharmacology 2011, 214, 829-841
32. Gillaspy, M. L.; Lefker, B. A.; Hada, W. A.; Hoover, D. J. A simple method for the formation of cyclopropylamines: The first synthesis of tricyclopropylamine Tetrahedron Lett. 1995, 36, 7399-7402
33. 3 receptor antagonists J. Med. Chem. 2004, 47, 2833-2838
34. Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. Rational development of practical catalysts for aromatic carbon-nitrogen bond formation Acc. Chem. Res. 1998, 31, 805-818
35. Nafie, L. A.; Dukor, R. K. In Applications of Vibrational Optical Activity in the Pharmaceutical Industry; Pivonka, D. E.; Chalmers, J. M.; Griffiths, P. R., Eds.; John Wiley and Sons: Chichester, West Sussex, England, 2007; pp 129-154.
36. Crawford, T. D. Ab initio calculation of molecular chirooptical properties Theor. Chem. Acc. 2006, 115, 227-245
37. Wesolowski, S. S.; Pivonka, D. E. A rapid alternative to X-ray crystallography for chiral determination: Case studies of vibrational circular dichroism (VCD) to advance drug discovery projects Bioorg. Med. Chem. Lett. 2013, 23, 4019-4025
38. Kaneko, T.; Clark, R. S. J.; Ohi, N.; Ozaki, F.; Kawahara, T.; Kamada, A.; Okano, K.; Yokohama, H.; Ohkuro, M.; Muramoto, K.; Takenaka, O.; Kobayashi, S. Piperidine carboxylic acid derivatives of 10 H -pyrazino[2,3- b ][1,4]benzothiazine as orally-active adhesion molecule inhibitors Chem. Pharm. Bull. 2004, 52, 675-687
39. 3 receptor Neuropharmacology 2002, 42, 929-940
40. 35S]GTPγS scintillation proximity assay for the high-throughput screening of Gi-linked G protein-coupled receptors Assay Drug Dev. Technol. 2003, 1, 261-273
41. Bernstein, P.; Ciaccio, P.; Morelli, J. Drug induced phospholipidosis Annu. Rep. Med. Chem. 2011, 46, 419-430
42. Mesens, N.; Steemans, M.; Hansen, E.; Verheyen, G. R.; Van Goethem, F.; Van Gompel, J. Screening for phospholipidosis induced by central nervous drugs: Comparing the predictivity of an in vitro assay to high throughput in silico assays Toxicol. In Vitro 2010, 24, 1417-1425
43. Sydserff, S.; Sutton, E. J.; Song, D.; Quirk, M. C.; Maciag, C.; Li, C.; Jonak, G.; Gurley, D.; Gordon, J. C.; Christian, E. P.; Doherty, J. J.; Hudzik, T.; Johnson, E.; Mrzljak, L.; Piser, T.; Smagin, G. N.; Wang, Y.; Dan Widzowski, D.; Smith, J. S. Selective α7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes Biochem. Pharmacol. 2009, 78, 880-888
44. 3 receptor agonists and their preparation, pharmaceutical compositions and use in the treatment of diseases, PCT Int. Appl. WO 2008147314 A1, December 4, 2008.
45. MacroModel, version 10.2; Schrödinger, LLC: New York, 2013.
46. ROCS, version 3.1.2; OpenEye Scientific Software, Inc.: Santa Fe, NM, 2011.