N-(1-Methyl-5-indolyl)-N′-(3-methyl-5-isothiazolyl)urea: A Novel, High-Affinity 5-HT2B Receptor Antagonist

Journal of Medicinal Chemistry

Volumn 38, Issue 6, 1995, Pages 855-857

  Forbes, Ian T ^a   Jones, Graham E ^a   Murphy, Olive E ^a   Holland, Victoria ^a   Baxter, Gordon S ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 METHYL 5 INDOLYL) 3 (3 METHYL 5 ISOTHIAZOLYL)UREA; DRUG DERIVATIVE; INDOLE DERIVATIVE; N-(1-METHYL-5-INDOLYL)-N'-(3-METHYL-5-ISOTHIAZOLYL)UREA; SEROTONIN ANTAGONIST; SEROTONIN RECEPTOR; UREA;

ANIMAL; ARTICLE; HUMAN; METABOLISM; RAT; SYNTHESIS;

ANIMAL; HUMAN; INDOLES; RATS; RECEPTORS, SEROTONIN; SEROTONIN ANTAGONISTS; UREA;

EID: 0029646696     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00006a001     Document Type: Article

References (34)

1. Humphrey, P. P. A.; Hartig, P.; Hoyer, D. A Proposed New Nomenclature for 5-HT Receptors. Trends Pharmacol. Sci. 1992, 14, 233.
2. Foguet, M.; Hoyer, D.; Pardo, L. A.; Parekh, A.; Kluxen, F. W.; Kalkman, H. O.; Stuhmer, W.; Lubbert, H. Cloning and Functional Characterization of the Rat Stomach Fundus Serotonin Receptor. EMBO J 1992, 11, 3481.
3. Foguet, M.; Nguyen, H.; Le, H.; Lubbert, H. Structure of the Mouse 5-HT1C, 5-HT2 and Stomach Fundus Serotonin Receptor Genes. Neuroreport 1992, 3, 345.
4. Kursar, J. D.; Nelson, D. L.; Wainscott, D. B.; Cohen, M. L.; Baez, M. Molecular Cloning, Functional Expression and Pharmacological Characterization of a Novel Serotonergic Receptor (5-HT2f) From Rat Stomach Fundus. Mol. Pharmacol. 1992, 42, 549.
5. Wainscott, D. B.; Cohen, M. L.; Schenck, K. W.; Adia, J. E.; Nissen, J. S.; Baez, M.; Kursar, J. D.; Lucaites, V. L.; Nelson, D. L. Pharmacological Characteristics of The Newly Cloned 5-HT2F Receptor. Mol. Pharmacol. 1993, 43, 419.
6. Baxter, G. S.; Murphy, O. E.; Blackburn, T. P. Further Characterisation of 5-Hydroxytryptamine Receptors in Rat Stomach Fundus Longitudinal Muscle. Br. J. Pharmacol. 1994, 112, 323
7. 2B-like Receptors Mediate Endothelium Dependent Relaxation of Rat Jugular Vein. Br. J. Pharmacol. 1994, 112 (Suppl.), 477P.
8. Kursar, J. D.; Nelson, D. L.; Wainscott, D. B.; Baez, M. Molecular Cloning, Functional Expression, and mRNA Tissue Distribution of The Human 5-HT2B Receptor. Mol. Pharmacol. 1994, 46, 227.
9. Schmuck, K.; Ullmer, C.; Engels, P.; Lubbert, H. Cloning and Functional Characterisation of The Human 5-HT2B Serotonin Receptor. FEBS Lett. 1994, 342, 85.
10. 1c Receptors. Br. J. Pharmacol. 1986, 88, 367P.
11. Clineschmidt, B. V.; Reiss, D. R.; Pettibone, D. J.; Robinson, J. L. Characterization of 5-Hydroxytryptamine Receptors in Rat Stomach Fundus. J. Pharmacol. Exp. Ther. 1985, 235, 696.
12. Cohen, M. L.; Wittenauer, L. A. Relationship Between Serotonin and Tryptamine Receptors in the Rat Stomach Fundus. J. Pharmacol. Exp. Ther. 1985, 233, 75.
13. Nelson, D. L. The 5-HT2 Subfamily of Receptors: Pharmacological Challenges. Med. Chem. Res. 1993, 3, 306.
14. 2b or 5-HT2C Receptor Blockade? Life Sci. 1994, 54, 641.
15. Fozard, J. R.; Kalkman, H. O. 5-HT and The Initiation of Migraine: New Perspectives. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1994, 350, 225.
16. 1c Receptor Antagonist. J. Med. Chem. 1993, 36, 1104.
17. Wood, M. D.; Glen, A.; Murphy, O. E.; Stewart, B. R.; Blackburn, T. P. SB 200646A: A Selective 5-HT2C Receptor Antagonist. Br. J. Pharmacol. 1994, 111 (Suppl.), 144P.
18. Kennett, G. A.; Wood, M. D.; Glen, A.; Grewal, S.; Forbes, I. T.; Gadre, A.; Blackburn, T. P. In Vivo Properties of SB 200646A, A 5-HT2C Receptor Antagonist. Br. J. Pharmacol. 1994, 111, 797.
19. Forbes, I. T.; Martin, R. T.; Jones, G. E. WO Patent 93/18028, published 16 September 1993.
20. Bordwell, F. G.; Stange, H. Benzothiophene Chemistry VII. Substitution Reactions of 5-Hydroxy and 5-Aminobenzothiophene Derivatives. J. Am. Chem. Soc. 1955, 77, 5939.
21. MartinSmith, M.; Gates, M. Benzothiophene-4, 5-quinones. J. Am. Chem. Soc. 1956, 78, 5351.
22. Pazos, A.; Hoyer, D.; Palacios, J. M. The Binding of Serotonergic Ligands to the Porcine Choroid Plexus: Characterization of a New Type of Serotonin Recognition Site. Eur. J. Pharmacol. 1984, 106, 539.
23. 3H]-Ketanserin (R41468), a Selective Tritiated Ligand for Serotonin 2 Receptor Binding Sites. Mol. Pharmacol. 1982, 21, 301.
24. 3H]-8-Hydroxy-2-(di-n-propylamino) tetralin Binding to Pre-and Post-synaptic 5-Hydroxytryptamine Sites in Various Regions of the fiat Brain. J. Neurochem. 1985, 44, 1685.
25. Waeber, C.; Schoeffer, P.; Palacios, J. M.; Hoyer, D. õ-HTm Receptor in Guinea-pig and Pigeon Brain. Radioligand Binding and Biochemical Studies. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1989, 340, 479.
26. Hamblin, M. W.; Metcalf, M. A. Primary Structure and Functional Characterisation of a Human 5-HTm-type Serotonin Receptor. Mol. Pharmacol. 1991, 40, 143.
27. 3H]-BRL 43694 (Granisetron), a Specific Ligand for 5-HT3 Binding Sites in Rat Brain Cortical Membranes. Biochem. Pharmacol. 1989, 38, 1693.
28. 4 Receptors. Br. J. Pharmacol. 1993, 110, (Suppl.), 10P.
29. Wardle, K. A.; Ellis, E. S.; Baxter, G. S.; Kennett, G. A.; Gaster, L. M.; Sanger, G. J. The Effects of SB 204070, A Highly Potent and Selective 5-HT4 Receptor Antagonist, on Guinea-pig Distal Colon. Br. J. Pharmacol. 1994, 112, 789.
30. Bowen, W. P.; Caldwell, M. C.; Hicks, F. R.; Riley, G. J. Further Characterisation of Human D2 and D3 Dopamine Receptors: GppNHp Shifts Are Explained by the Presence of More Than One Binding Site in Each Clone. Br. J. Pharmacol. 1993, 108 (Suppl.), 277P.
31. 3H]-Mepyramine. Eur. J. Pharmacol. 1978, 48, 463.
32. 3H]-Prazosin Binds Specifically to α. ι Adrenoceptors in Rat Brain. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1980, 312, 23.
33. Renouard, A.; Widdowson, P. S.; Cordi, A. Tritiated Idazoxan Binding to Rabbit Cerebral Cortex Recognises Multiple Imidazoline 12-type Receptors. Br. J. Pharmacol. 1993, 109, 625.
34. Peters, J. A.; Kirkness, E. F.; Callachan, H.; Lambert, J. J.; Turner, A. J. Modulation of the GABAa Receptor by Depressant Barbiturates and Pregnone Steroids. Br. J. Pharmacol. 1988, 94, 1257.