Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: Optimising brain penetration

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 1, 2008, Pages 262-266

  Peters, Jens Uwe ^a   Lübbers, Thomas ^a   Alanine, Alexander ^a   Kolczewski, Sabine ^a   Blasco, Francesca ^b   Steward, Lucinda ^b  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

5 HT; DMPK; GPCR; Guanidine; Molecular properties

Indexed keywords

GUANIDINE DERIVATIVE; LIGAND; SEROTONIN 1A RECEPTOR; SEROTONIN 1D RECEPTOR; SEROTONIN 2C RECEPTOR; SEROTONIN 5A RECEPTOR; SEROTONIN 7 RECEPTOR;

ARTICLE; CONCENTRATION RESPONSE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG USE; ENANTIOMER; LIGAND BINDING; LIPOPHILICITY; NONHUMAN; PHYSICAL CHEMISTRY; PKA; REACTION OPTIMIZATION; SEPARATION TECHNIQUE; SEROTONIN RELEASE; X RAY CRYSTALLOGRAPHY;

ANIMALS; BLOOD-BRAIN BARRIER; BRAIN; GUANIDINES; HUMANS; KINETICS; LIGANDS; MODELS, MOLECULAR; PYRIMIDINES; QUINAZOLINES; RATS; RECEPTORS, SEROTONIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 37549014908     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.10.078     Document Type: Article

References (23)

1. Lanfumey L., and Hamon M. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 1
2. Costall B., and Naylor R.J. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 27
3. Bockaert J., Claeysen S., Compan V., and Dumuis A. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 39
4. Woolley M.L., Marsden C.A., and Fone K.C.F. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 59
5. Thomas D.R., and Hagan J.J. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 81
6. Oliver K.R., Kinsey A.M., Wainwright A., and Sirinathsinghji D.J.S. Brain Res. 867 (2000) 131
7. Iwata N., Ozaki N., Inada T., and Goldman D. Mol. Psychiatry 6 (2001) 217
8. Arias B., Collier D.A., Gasto C., Pintor L., Gutierrez B., Valles V., and Fananas L. Neurosci. Lett. 303 (2001) 111
9. Birkett J.T., Arranz M.J., Munro J., Osbourn S., Kerwin R.W., and Collier D.A. NeuroReport 11 (2000) 2017
10. Nelson D.L. Curr. Drug Targets CNS Neurol. Disord. 3 (2004) 53
11. Thomas D.R. Pharmacol. Ther. 111 (2006) 707
12. Data presented at the 36th Annu. Meet. Soc. Neurosci., October 14-18, Atlanta, 2006. (a) Garcia-Ladona, F.; Amberg, W.; Kling, A.; Lange, U. E. W.; Hornberger, W.; Wernet, W.; Netz, A.; Ochse, M.; Mezler, M.; Meyer, A. H.; Hahn, A.; Hillen, H.; Beyerbach, A.; Bowmik, S.; Schoemaker, H.; Sullivan, J. P. Abst. 33.1.
13. Drescher, K. U.; Amberg, W.; Kling, A.; Gross, G.; Schoemaker, H.; Sullivan, J. P.; Garcia-Ladona F. J. Abst. 33.2.
14. Rueter, L. E.; Wicke, K.; Basso, A. M.; Jongen-Relo, A. L.; van Gaalen, M. M.; Gross, G.; Decker, M. W.; Kling, A.; Schoemaker, H.; Sullivan, J. P.; Amberg, W.; Garcia-Ladona, F. J. Abst. 33.3.
15. Ebert, U.; Kling, A.; Amberg, W.; Garcia-Ladona, F. J.; G. Gross, G.; Schoemaker, H.; Sullivan, J. P. Abst. 529.25.
16. Jongen-Relo, A. L.; Bespalov, A. Y.; Rueter, L. E.; Freeman, A. S.; Decker, M. W.; Gross, G.; Schoemaker, H.; Sullivan, J. P.; van Gaalen, M. M.; Wicke, K. M.; Zhang, M.; Amberg, W.; Garcia-Ladona, F. J. Abst. 529.26.
17. a = 9.5-10.
18. Van de Waterbeemd H., Smith D.A., and Jones B.C. J. Comput. Aided Mol. Des. 15 (2001) 273
19. Hitchcock S.A., and Pennington L.D. J. Med. Chem. 49 (2006) 7559
20. Atkinson F., Cole S., Green C., and Van de Waterbeemd H. Curr. Med. Chem. Centr. Nerv. Syst. Agents 2 (2002) 229
21. Measurements were performed according to an in-house developed miniaturized method to measure the shake flask octanol-water partition coefficient at pH 7.4 (log D).
22. Meylan W.M., and Howard P.H. J. Pharm. Sci. 84 (1995) 83
23. Smith D.A., van de Waterbeemd H., and Walker D.K. In: Mannhold R., Kubinyi H., and Timmerman H. (Eds). Pharmacokinetics and Metabolism in Drug Design (2003), Wiley-VCH, Weinheim