Selective naphthalene H3 receptor inverse agonists with reduced potential to induce phospholipidosis and their quinoline analogs

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 15, 2009, Pages 4495-4500

  Rodríguez Sarmiento, Rosa María ^a   Nettekoven, Matthias H ^a   Taylor, Sven ^a   Plancher, Jean Marc ^a   Richter, Hans ^a   Roche, Olivier ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Amphiphilic vector; Amphiphilicity; Histamine H3 receptor; Naphthalene; Pharmacophore model; Phospholipidosis; Quinoline; SAR

Indexed keywords

(3 PIPERIDIN 1 YL PROPOXY) NAPHTHALENE DERIVATIVE; HISTAMINE AGONIST; HISTAMINE H1 RECEPTOR; HISTAMINE H2 RECEPTOR; HISTAMINE H3 RECEPTOR; HISTAMINE H4 RECEPTOR; NAPHTHALENE DERIVATIVE; PHOSPHOLIPID; QUINOLINE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; INVERSE AGONISM; LIPIDOSIS; PHARMACOPHORE; PKA; STRUCTURE ACTIVITY RELATION;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HISTAMINE AGONISTS; HUMANS; HYDROGEN-ION CONCENTRATION; MODELS, CHEMICAL; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; NAPHTHALENES; PHOSPHOLIPIDS; PROTEIN BINDING; QUINOLINES; RATS; RECEPTORS, HISTAMINE H3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 67649968886     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.100     Document Type: Article

References (46)

1. Parsons M.E., and Ganellin C.R. Br. J. Pharmacol. 147 (2006) S127
2. Hough L.B. Mol. Pharmacol. 59 (2001) 415
3. Hill S.J., Ganellin C.R., Timmermann H., Schwartz J.C., Shankley N.P., Young J.M., Schunack W., Levi R., and Haas H.L. Pharmacol. Rev. 49 (1997) 253
4. Leurs R., Church M.K., and Taglialatela M. Clin. Exp. Allergy 32 (2002) 489
5. Ganellin C.R. J. Med. Chem. 24 (1981) 913
6. Schunack W. J. Int. Med. Res. 17 (1989) 9A
7. Zhang M., Thurmond R.L., and Dunford P.J. Pharmacol. Therap. 113 (2007) 594
8. De Esch I.J.P., Thurmond R.L., Jongejan A., and Leurs R. Trends Pharmacol. Sci. 26 (2005) 462
9. Jablonowski J.A., Carruthers N.I., and Thurmond R.L. Mini-Rev. Med. Chem. 4 (2004) 993
10. Arrang J.M., Garbarg M., and Schwartz J.C. Nature 302 (1983) 832
11. Arrang J.M., Garbarg M., and Schwartz J.C. Neuroscience 23 (1987) 149
12. 3 Receptor; A Target for New Drugs. 1st Ed. (1998), Elservier Science B.V., Amsterdam 13-26
13. Leurs R., Blandina P., Tedford C., and Timmermann H. Trends Pharmacol. Sci. 19 (1998) 177
14. Blandina P., Giorgett M., Bartoli L., Cecchi M., Timmermann H., and Leurs R. Br. J. Pharmacol. 119 (1996) 1656
15. Di Carlo G., Ghi P., and Orsetti M. Prog. Neuropsychopharmacol. Biol. Psychiatry 24 (2000) 275
16. Medhurst A.D., Atkins A.R., Beresford I.J., Brackenborough K., Briggs M.A., and Calver A.R. J. Pharmacol. Exp. Ther. 321 (2007) 1032
17. Threlfell S., Cragg S.J., Kallo I., Tur G.F., Coen C.W., and Greenfield S.A. J. Neurosci. 24 (2004) 8704
18. Fox G.B., Esbenshade T.A., Pan J.B., Radex R.J., Krueger K.M., and Yao B.B. J. Pharmacol. Exp. Ther. 313 (2005) 176
19. Ligneau X., Perrin D., Landais L., Camelin J.C., Calmels T.P.G., and Berrebi B.I. J. Pharmacol. Exp. Ther. 320 (2007) 320
20. Esbenshade T.A., Browman K.E., Bitner R.S., Strakhova M., Cowart M.D., and Brioni J.D. Br. J. Pharmacol. 154 (2008) 1
21. Celanire S., Wijtmans M., Talaga P., Leurs R., and de Esch I.J. Drug Discovery Today 10 (2005) 1613
22. Esbenshade T.A., Fox G.B., and Cowart M.D. Mol. Interventions 6 (2006) 77
23. Passani M.B., Lin J.S., Hancock A., Crochet S., and Blandina P. Trends Pharmacol. Sci. 25 (2004) 618
24. For most recent development status please check: www.prous.com.
25. Ishizuka T., Hatano K., Murotani T., and Yamatodani A. Behav. Brain Res. 188 (2008) 250
26. Masaki T., and Yoshimatsu H. Mini-Rev. Med. Chem. 7 (2007) 821
27. Hancock A.A., and Brune M.E. Expert Opin. Invest. Drugs 14 (2005) 223
28. Roche O., and Rodriguez-Sarmiento R.M. Bioorg. Med. Chem. Lett. 17 (2007) 3670
29. Roche O., Nettekoven M., Vivian W., and Rodriguez-Sarmiento R.M. Bioorg. Med. Chem. Lett. 18 (2008) 4377
30. Solubility measurements were performed by a method developed in house from a 10 mM DMSO stock solution. This method is similar to the classical thermodynamic shake-flask solubility, with the only difference being that DMSO is removed before measurement by an additional lyophilization step. The assay is called lyophilizated solubility assay (LYSA).
31. Measurements were performed according to. Kansy M., Senner F., and Gubernator K. J. Med. Chem. 41 (1998) 1007
32. Measurements were performed according to. Obach R.S., Baxter J.G., Liston T.E., Silber B.M., Jones B.C., MacIntyre F., Rance D.J., and Wastall P. J. Pharm. Exp. Ther. 283 (1997) 46
33. Genotoxicity is estimated with the use of the AMES microsuspension assay, where the read-out parameter is the increase in the number of revertant colonies (mutation frequency) of treated compared to untreated control in five different Salmonella typhimurium tester strains.The micronucleus in vitro test (MNT in vitro test) is used to detect chromosomal damage. The read-out parameter is the increase in the number of micronucleated cells (%) of treated compared to untreated control in cultivated mammalian cells.
34. a value reflecting the cationic nature of the molecule and it's amphiphilicity that is defined as the distance between the charged residue and the more remote hydrophobic residues. For a more detailed description see:. Muster W., Breidenbach A., Fischer H., Kirchner S., Mueller L., and Paehler A. Drug Discovery Today 13 (2008) 303
35. Handrock K., Lüllmann-Rauch R., and Vogt R.D. Toxicology 85 (1993) 199
36. Lüllmann-Rauch R., Pods R., and von Witzendorff B. Toxicology 110 (1996) 27
37. Mason R.J., Walker S.R., Shields B.A., Henson J.E., and Williams M.C. Am. Rev. Respir. Dis. 131 (1985) 786
38. 50 based on the Cheng-Prusoff equation: Cheng, Y; Prusoff, W. H. Biochem. Pharmacol. 1973, 22, 3099. For a more detailed description see: Gatti, S.; Hertel,C.; Nettekoven, M.; Plancher, J.-M.; Raab, S.; Roche, O.; Rodriguez-Sarmiento, R.-M. PCT Int. Appl. 2005, WO2005117865.
39. 35S binding was performed in 96-well microplates in a total volume of 180 μL with 30 μg membrane proteins and 0.28 nM GTPγ35S. Nonspecific binding was measured in the presence of 10 μM cold GTPγS. Plates were sealed and agitated (350 rpm) at room temperature for 2 h. The beads were then settled by centrifugation (1000 rpm, 10 min) and the plate counted in a top count using quench correction.
40. Reasor M.J., and Kacew S. Exp. Biol. Med. 226 (2001) 825
41. Hancock A.A. Biochem. Pharmacol. 71 (2006) 1103
42. AM > -6 kJ/mol showed no potential hazard in the phospholipidosis assay. With this approach approximately 80% of the positive and negative in vitro findings could be classified correctly. For a more detail description see: Fischer, H.; Kansy, M.; Potthast, M.; Csato, M. In Proceedings of the 13th European Symposium on Quantitative Structure-Activity Relationships, Duesseldorf, Germany, August 27-September 1, 2000; Prous Science: Barcelona, Spain, 2001.
43. AM). For a more detail description, see:. Fischer H., Kansy M., and Bur D. Chimia 54 (2000) 640
44. Measurements were performed according to:. Allen R.I., Box K.J., Comer J., Peake C., and Tam K.Y. J. Pharm. Biomed. Anal. 17 (1998) 699
45. Boger D., and Panek J. J. Am. Chem. Soc. 107 (1985) 5745
46. Montanari F., and Pentimalli L. Gazz. Chim. Ital. 83 (1953) 273