Novel selective and partial agonists of 5-HT3 receptors. Part 1. Synthesis and biological evaluation of piperazinopyrrolothienopyrazines

Journal of Medicinal Chemistry

Volumn 39, Issue 10, 1996, Pages 2068-2080

  Rault, Sylvain ^a   Lancelot, Jean Charles ^a   Prunier, Hervé ^a   Robba, Max ^a   Renard, Pierre ^b   Delagrange, Philippe ^c   Pfeiffer, Bruno ^b   Caignard, Daniel Henri ^b   Guardiola Lemaitre, Béatrice ^c   Hamon, Michel ^d  

^a CENTRE D ETUDES ET DE RECHERCHE SUR LE MÉDICAMENT DE NORMANDIE   (France)

^b ADIR   (France)

^c INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

^d PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

5 (4 ALLYLPIPERAZINO)PYRROLO[1,2 A]THIENO[2,3 E]PYRAZINE TRIHYDROCHLORIDE; 5 (4 BENZYLPIPERAZINO)PYRROLO[1,2 A]THIENO[2,3 E]PYRAZINE TRIHYDROCHLORIDE; 5 (4 BENZYLPIPERAZINO)PYRROLO[1,2 A]THIENO[3,2 E]PYRAZINE; 5 [4 (4 FLUOROBENZYL)PIPERAZINO]PYRROLO[1,2 A]THIENO[2,3 E]PYRAZINE; 5 PIPERAZINOPYRROLO[1,2 A]THIENO[2,3 E]PYRAZINE DERIVATIVE; 5 PIPERAZINOPYRROLO[1,2 A]THIENO[3,2 E]PYRAZINE; 5 PIPERAZINOPYRROLO[1,2 A]THIENO[3,2 E]PYRAZINE DERIVATIVE; ANXIOLYTIC AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DOSE RESPONSE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; MALE; MOUSE; NONHUMAN; RAT; RECEPTOR AFFINITY; SEROTONIN RELEASE; STRUCTURE ANALYSIS; TRANQUILIZING ACTIVITY;

ANIMALS; CATTLE; CHOROID PLEXUS; FRONTAL LOBE; HIPPOCAMPUS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; PYRAZINES; RATS; RECEPTORS, SEROTONIN; RECEPTORS, SEROTONIN, 5-HT3; SEROTONIN AGONISTS; SWINE;

EID: 15844421030     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950543x     Document Type: Article

References (50)

1. Rapport, M. M.; Green, A. A.; Page, I. H. Purification of the substance which is responsible for vasoconstrictor activity of serum. Fed. Proc. 1947, 6, 184.
2. Vialli, M.; Erspamer, V. Cellule enterocromaffini e cellule basigranulose acidofile nei vertebrati. Mikrosk. Anat. 1933, 19, 743.
3. Martin, G. R.; Humphrey, P. P. A. Classification Review Receptors for 5-hydroxytryptamine: Current Perspectives on Classification and Nomenclature. Neuropharmacology 1994, 33, 261-273.
4. Hoyer, D.; Clarke, D. E.; Fozard, J. R.; Harting, P. R.; Martin, G. R.; Mylecharane, E. J.; Saxena, P. R.; Humphrey, P. A. VII International Union of Pharmacology Classification of Receptors for 5-Hydroxytryptamine (Serotonin). Pharmacol. Rev. 1994, 46, 157-203.
5. Zifa, E.; Fillion, G. 5-Hydroxytryptamine Receptors. Pharmacol. Rev. 1992, 44, 401-458.
6. 3 Receptors. Med. Res. Rev. 1990, 10, 441-475.
7. Sanger, G. J.; Nelson, G. R. Selective and functional 5-hydroxytryptamine receptor antagonism by BRL 43694 (Granisetron). Eur. J. Pharmacol. 1989, 159, 113-124.
8. 3 receptors. Br. J. Pharmacol. 1988, 94, 387-412.
9. Richardson, B. P.; Engel, G.; Donatsch, P.; Stadler, P. A. Identification of serotonin m-receptor subtypes and their specific blockade by a new class of drugs. Nature 1985, 316, 126-131.
10. 3 receptor antagonists. An overview of their present status and future potential in cancer therapy-induced emesis. Drugs 1991, 42, 551-568.
11. 3 receptor antagonists: a critical update on therapeutic potential. Trends Pharmacol. Sci. 1993, 14, 265-270.
12. 3 receptor agonist. Eur. J. Pharmacol. 1990, 182, 193-197.
13. 3 Receptor Agonists 1-phenyl biguanide and m-chlorophenylbiguanide in Rats. J. Pharmacol. Exp. Ther. 1993, 264, 1440-1449.
14. 3H] granisetron. Biochem. Pharmacol. 1993, 45, 2155-2158.
15. 3H]-GR 65630 binding. Br. J. Pharmacol. 1991, 102, 919-925.
16. 3 serotonin receptors: results of a structure-affinity study. Eur. J. Pharmacol. 1989, 168, 387-392.
17. 3 Receptor Ligands and Substance P. J. Neurochem. 1993, 60, 2059-2061.
18. 3 Receptors. Synthesis and Biological Evaluation of Piper-azinylquinoxaline Derivatives. J. Med. Chem. 1993, 36, 2745-2750.
19. 4 agonist properties. J. Med. Chem. 1994, 37, 1320-1325.
20. 3 Antagonists. Chem. Pharm. Bull. 1993, 41, 1832-1941.
21. Neale, R. F.; Fallon, S. L.; Boyar, W. C.; Wasley, J. W. F.; Martin, L. L.; Stone, G. A.; Glaeser, B. S.; Sinton, C. M.; Williams, M. Biochemical and pharmacological characterization of CGS 12066B a selective serotonin-1b agonist. Eur. J. Pharmacol. 1987, 136, 1-9.
22. Rault, S.; Cugnon de Sevricourt, M.; Robba, M. New condensed triheterocyclic systems: pyrrolothienopyrazines. Heterocycles 1980, 14, 651.
23. Rault, S.; Effi, Y.; Cugnon de Sevricourt, M.; Lancelot, J. C.; Robba, M. Pyrrolothiénopyrazines: synthèse de la pyrrolo[1,2-a]thiéno[3,2-e]pyrazine et de la pyrrolo[1,2-a]thiéno[2,3-e]pyrazine. (Pyrrolothienopyrazines: synthesis of pyrrolo[1,2-a]thieno-[3,2-e]pyrazine and pyrrolo[1,2-a]thieno[2,3-e]pyrazine.) J. Heterocycl. Chem. 1983, 20, 17-21.
24. Effi, Y.; Lancelot, J. C.; Rault, S.; Robba, M. Pyrrolothiénopyrazines: étude de l'oxo-5 pyrrolo[1,2-a]thiéno[2,3-e]pyrazine. (Pyrrolo[1,2-a]thieno[2,3-e]pyrazine. Chemical study of 4,5-dihydropyrrolo[1,2-a]thieno[2,3-e]pyrazin-5-one.) J. Heterocycl. Chem. 1983, 20, 913-918.
25. Rioult, J. P.; Cugnon de Sevricourt, M.; Rault, S.; Robba, M. Pyrrolothiénopyrazines: étude chimique de la pyrrolo[1,2-a]thiéno-[3,2-e] pyrazine. (Pyrrolothienopyrazines: chemical study of pyrrolo[1,2-a]thieno[3,2-e]pyrazine.) J. Heterocycl. Chem. 1984, 21, 1449.
26. Effi, Y.; Lancelot, J. C.; Rault, S.; Robba, M. Pyrrolothiénopyrazines: étude chimique de la pyrrolo[1,2-a]thiéno[2,3-e] pyrazine. (Pyrrolothienopyrazines: chemistry of pyrrolo[1,2-a]-thieno[2,3-e]pyrazine.) J. Heterocycl. Chem. 1986, 23, 17-23.
27. Effi, Y.; Lancelot, J. C.; Rault, S.; Robba, M. Pyrrolothiénopyrazines. IV. Synthèse de dérivés de l'amino-5 pyrrolo[1,2-a] thiéno[2,3-e]pyrazine. (Pyrrolothienopyrazines. IV. Synthesis of 5-aminopyrrolo[1,2-a]thieno[2,3-e]pyrazine derivatives.) J. Heterocycl. Chem. 1987, 24, 431-435.
28. Rault, S.; Cugnon de Sevricourt, M.; Nguyen-Huy, D.; Robba, M. Pyrrolo[1,2-a]thieno[3,2-e]pyrazines. J. Heterocycl. Chem. 1981, 18, 739-742.
29. Rault, S.; Lancelot, J. C.; Pilo, J. C.; Robba, M.; Renard, P.; Guardiola, B.; Adam, G. Nouveaux composés pyrrolothiénopyraziniques, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent. EP 573360 (ADIR et Cie).
30. Gewald, K. 2-Aminothiophene aus α-oxo-mercaptenen und methylenaktiven nitrilen. Chem. Ber. 1965, 98, 3571-3577.
31. Clauson-Kaas, N.; Tyle, Z. Preparation of cis and trans 2.5-dimethoxy-2-(acetamidomethyl)-2.5-dihydrofuran, of cis and trans 2.5-dimethoxy-2-(acetamidomethyl)-tetrahydrofuran and of 1-phenyl2-(acetamidomethyl)-pyrrole. Acta Chem. Scand. 1952, 6, 667-670.
32. Elming, N.; Clauson-Kaas, N. The preparation of pyrroles from furans. Acta Chem. Scand. 1952, 6, 867-874.
33. Liebscher, J.; Neumann, B.; Hartmann, H. Eine einfache synthese von β-chlorzimtsäurenitrilen nach einer modifizierten Vilsmeier-Haack-Arnold reaktion. (A simple synthesis of β-chlorocinnamonitriles by a modified Vilsmeier-Haack-Amold reaction.) J. Prakt. Chem. 1983, 325, 915.
34. Hartmann, H.; Liebscher, J. A simple method for the synthesis of 5-aryl-3-amino-2-alkoxycarbonylthiophenes. Synthesis 1984, 275-277.
35. Huddleston, P. R.; Barker, J. M. A convenient synthesis of 2-substituted 3-hydroxy and 3-aminothiophenes from derivatives of 2-chloroacrylic acid. Synth. Commun. 1979, 9, 731-734.
36. 3H. Chem. Ber. 1890, 23, 3023-3033.
37. Curtius, T. J. Prakt. Chem. 1894, 50, 275.
38. Gewald, K.; Schinke, E.; Böttcher, H. 2-Aminothiophene aus methylenaktiven nitrilen, carbonylverbindungen und Schwefel. Chem. Ber. 1966, 99, 94-100.
39. Vilsmeier, A.; Haack, A. Über die einwirkung von halogenphosphor auf alkyl-formanilide. Eine neue methode zur darstellung sekundärer und tertiärer p-alkylamino-benzaldehyde. Chem. Ber. 1927, 60, 119-122.
40. Kirsch, G.; Cagniant, D.; Cagniant, P. Synthèse d'amino-3 thiophènes à partir d'aryl- et d'hetaryl-acétonitrile (1). (Syntheses of 3-aminothiophenes from aryl- and hetarylacetonitriles.) J. Heterocycl. Chem. 1982, 19, 443-444.
41. Rault, S.; Lancelot, J. C.; Letois, B.; Robba, M.; Labat, Y. French Patent No. 92 037 32, Mar. 27, 1992.
42. Misslin, R.; Beizung, C.; Vogel, E. Behavioural validation of a light/dark choice procedure for testing anti-anxiety agents. Behav. Process 1989, 18, 119-132.
43. 3H]-ketanserin. Eur. J. Pharmacol. 1985, 118, 13-23.
44. 1C binding sites in rat frontal cortex. J. Neurochem, 1986, 47 (2), 529-540.
45. 1D receptor: A progress review. Neurochem. Res. 1990, 15, 6, 567-582.
46. 3H]-Ketanserin (R41468), a selective 3H-ligand for serotonin 2 receptor binding sites; binding properties, brain distribution and functionnal role. Mol. Pharmacol. 1982, 21, 301.
47. 2 antagonists block 5HT1C receptors in choroïd plexus. J. Pharmacol. Exp. 1988, 247, 169.
48. 3 recognition sites by radioligand binding in NG108-15 neuroblastomaglioma cells. Eur. J. Pharmacol. 1987, 143, 291-292.
49. Costall, B.; Jones, B. J.; Kelly, M. E.; Naylor, R. J.; Tomkins, D. M. Exploration of mice in black and white test box: validation as a model of anxiety. Pharmacol. Biochem. Behav. 1989, 777, 32.
50. 3 receptor antagonist. Br. J. Pharmacol. 1988, 93, 985.