Arylpipirazide derivatives of phenylpiperazines as a new class of potent and selective 5-HT(1B) receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 24, 1997, Pages 3183-3188

  Jorand Lebrun, C ^a   Pauwels, P J ^a   Palmier, C ^a   Chopin, P ^a   Moret, C ^a   Marien, M ^a   Halazy, S ^a  

^a INSTITUT DE RECHERCHE PIERRE FABRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2,3,6,7 TETRAHYDRO 1' METHYL 5 [[2' METHYL 4' (5 METHYL 1,2,4 OXADIAZOL 3 YL) 4 BIPHENYLYL]CARBONYL]SPIRO[FURO[2,3 F]INDOLE 3,4' PIPERIDINE]; 4 (2 METHOXYPHENYL)PIPERAZINE 1 N [4 METHOXY 3 (4 METHYLPIPERAZINO)PHENYL]CARBOXAMIDE; ANTIDEPRESSANT AGENT; N [4 METHOXY 3 (4 METHYL 1 PIPERAZINYL)PHENYL] 2' METHYL 4' (5 METHYL 1,2,4 OXADIAZOL 3 YL)[1,1' BIPHENYL] 4 CARBOXAMIDE; PIPERAZINE DERIVATIVE; RECEPTOR SUBTYPE; SEROTONIN 1B ANTAGONIST; SEROTONIN 1B RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DOSE RESPONSE; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; GUINEA PIG; HUMAN; HYPOTHERMIA; IN VITRO STUDY; INFRARED SPECTROPHOTOMETRY; INTRAPERITONEAL DRUG ADMINISTRATION; MASS SPECTROMETRY; MICRODIALYSIS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ORAL DRUG ADMINISTRATION; SEROTONIN BRAIN LEVEL; SEROTONIN RELEASE; STRUCTURE ACTIVITY RELATION;

ANIMALIA; CAVIA PORCELLUS; SUS SCROFA;

EID: 0031455978     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10164-0     Document Type: Article

References (20)

1. Halazy, S.; Lamothe, M.; Jorand-Lebrun, C. Exp. Opin. Ther. Pat. 1997, 7(4), 339.
2. Maes, M.; Meltzer, H.Y. In Psychopharmacology: the fourth generation of progress, edited by Bloom, F.E. and Kupfer, D.J. New York Raven Press, 1995, 933-934.
3. Blier, P.; De Montigny, C. Trends Pharmacol.Sci. 1994, 15, 220.
4. Briley, M.; Moret, C. Clin. Neuropharmacol. 1993, 16, 387.
5. Pauwels, P.J. General Pharmacology 1997, In press.
6. Pauwels, P.J. CNS Drugs Rev. 1996, 2, 415.
7. 1B receptor inverse agonist". 3rd Annual symposium on random and rationale drug discovery via combinatorial chemistry and structure-based design. Geneva, Switzerland, Oct. 1996.
8. Roberts, C.; Price, G.W.; Gaster, L.; Jones, B.J.; Middlemiss, D.N.; Routledge, C. Neuropharmacol. 1997, 36(4/5), 549.
9. Perez, M.; Pauwels, P.J.; Palmier, C.; John, G.W.; Valentin, J.-P.; Halazy, S. Bioorg.Med.Chem.Lett. 1995, 5, 663.
10. Perez, M.; Fourrier, C.; Sigogneau, I.; Pauwels, P.J.; Palmier, C.; John, G.W.; Valentin, J.-P.; Halazy, S. J.Med.Chem. 1995, 38, 3602.
11. Perez, M.; Pauwels, P.J.; Palmier, C.; John, G.W.; Valentin, J.-P.; Halazy, S. Med.Chem.Res. 1995, 5, 680.
12. Oxford, A.W.; Mitchell, W.L.; Bradshaw, J.; Clitherow, J.W.; Baxter, I.C. EP-0533 266 A1. 1992.
13. 1H NMR (DMSO) : 2.33 (s, 3H); 2.63 (m, 4H); 2.96 (m, 8H) 3.55 (m, 4H); 3.72 (s, 3H); 3.79 (s, 3H); 6.57 (s, 2H); 6.78-7.10 (m, 7H); 8.34 (s, 1H). Spectral data and physico-chemical caracteristics of the other compounds described herein have been reported in the patent application WO-9602525.
14. Pauwels, P. J.; Palmier, C.; Wurch, T.; Colpaert, F. C. Naunyn-Schmiedeberg's Arch. Pharmacol. 1996, 353, 144.
15. Pauwels, P. J.; Van Compel, P.; Leysen, J. E. Biochem. Pharmacol. 1993, 45, 375.
16. Pauwels, P. J.; Palmier, C.; Colpaert, F. C. Cell. Pharmacol. 1995, 2, 49.
17. Skingle, M.; Higgins, G. A.; Feniuk, W. J. Psychopharmacol. 1994, 8, 14.
18. Jorand-Lebrun, C.; Pauwels, P.J.; Palmier, C.; Moret, C.; Chopin, P.; Perez, M.; Marien, M.; Halazy, S. J. Med. Chem. 1997, in press.
19. Moret, C.; Briley, M. Naunyn-Schmiedeberg's Arch. Pharmacol. 1995, 351, 377.
20. Values are given as mean values of 3 to 5 independent experiments, typically with individual values within 20 % of the mean.