Potent, selective tetrahydro-β-carboline antagonists of the serotonin 2B (5HT(2B)) contractile receptor in the rat stomach fundus

Journal of Medicinal Chemistry

Volumn 39, Issue 14, 1996, Pages 2773-2780

  Audia, James E ^a   Evrard, Deborah A ^a   Murdoch, Gwyn R ^a   Droste, James J ^a   Nissen, Jeffrey S ^a   Schenck, Kathy W ^a   Fludzinski, Pawel ^a   Lucaites, Virginia L ^a   Nelson, David L ^a   Cohen, Marlene L ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SEROTONIN 1 RECEPTOR; TRYPTOLINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; DRUG POTENCY; DRUG SELECTIVITY; LIGAND BINDING; NONHUMAN; RAT; RECEPTOR AFFINITY; SEROTONIN BLOOD LEVEL; STOMACH FUNDUS; STRUCTURE ACTIVITY RELATION;

ANIMALS; CARBOLINES; CELL LINE; CRICETINAE; GASTRIC FUNDUS; MALE; MESOCRICETUS; MICE; MOLECULAR STRUCTURE; MUSCLE CONTRACTION; MUSCLE, SMOOTH; RATS; RATS, WISTAR; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTOR, SEROTONIN, 5-HT2B; RECEPTOR, SEROTONIN, 5-HT2C; RECEPTORS, SEROTONIN; SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP; YOHIMBINE;

EID: 8944239873     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960062t     Document Type: Article

References (54)

1. Cohen, M. L.; Fludzinski, L. A. Contractile serotoninergic receptor in rat stomach fundus. J. Pharmacol. Exp. Ther. 1987, 243, 264-9.
2. 1c receptor. Mol. Pharmacol. 1990, 38, 31-7.
3. Baxter, G. S.; Murphy, O. E.; Blackburn, T. P. Further characterization of 5-hydroxytryptamine receptors (putative). Br. J. Pharmacol. 1994, 112, 323-31.
4. Cohen, M. L.; Wittenauer, L. A. Relationship between serotonin and tryptamine receptors in the rat stomach fundus. J. Pharmacol. Exp. Ther. 1985, 233, 75-9.
5. Cohen, M. L.; Schenck, K. W.; Colbert, W.; Wittenauer, L. Role of 5HT2 receptors in serotonin-induced contractions of nonvascular smooth muscle. J. Pharmacol. Exp. Ther. 1985, 232, 770-4.
6. 2 and rat stomach fundus 5HT receptors. J. Pharmacol. Exp. Ther. 1986, 237, 713-18.
7. 1B. Life Sci. 1986, 38, 1-5.
8. 2α in rat stomach fundus. J. Pharmacol. Exp. Ther. 1989, 250, 971-8.
9. Humphrey, P. P. A.; Hartig, P.; Hoyer, D. A. A Proposed New Nomenclature of 5HT Receptors. Trends Pharmacol. Sci. 1992, 14, 233.
10. Foguet, M.; Hoyer, D.; Pardo, L. A.; Parekh, A.; Kluxen, F. W.; Kalkman, H. O.; Stuehmer, W.; Luebbert, H. Cloning and functional characterization of the rat stomach fundus serotonin receptor. EMBO J. 1992, 11, 3481-7.
11. 2F) from rat stomach fundus. Mol. Pharmacol. 1992, 42, 549-57.
12. 2B receptor. Mol. Pharmacol. 1994, 46, 227-34.
13. 2 and stomach fundus serotonin receptor genes. NeuroReport 1992, 3, 345-8.
14. 2B serotonin receptor. FEBS Lett. 1994, 342, 85-90.
15. 2F receptor. Mol. Pharmacol. 1993, 43, 419-26.
16. 2 Subfamily of Receptors: Pharmacological Challenges. Med. Chem. Res. 1993, 3, 306.
17. 2B Receptor Antagonist with Improved Affinity, Selectivity, and Oral Activity. J. Med. Chem. 1995, 38, 2524-2530.
18. 2A Receptor Affinity. J. Med. Chem. 1995, 38, 28-33.
19. 2B Receptor Antagonist. J. Med. Chem. 1995, 38, 855-7.
20. 2, and rat stomach fundal serotonin receptors. J. Med. Chem. 1988, 29, 2415-18.
21. 2C receptors. Br. J. Pharmacol. 1995, 115, 622-8.
22. 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, 696-708.
23. 2-adrenoreceptor. Pharmacol. Rev. 1983, 35, 143-80.
24. 2-adrenoreceptors in depression: a critical examination. J. Psychopharmacol. 1993, 7(1), 4-18.
25. Toke, L.; Honty, K.; Szantay, C. Total synthesis of (+)-yohimbine and (-)-β-yohimbine. Chem. Ber. 1969, 102, 3248-59.
26. Loewe, M. F.; Meyers, A. I. An asymmetric synthesis of indole alkaloids. Tetrahedron Lett. 1985, 26, 3291-4.
27. Rommelspacher, H.; Coper, H.; Strauss, S. On the mode of formation of tetrahydro-β-carbolines. Life Sci. 1976, 18, 81-8.
28. Kametani, T.; Takeshita, M.; Satoh, F. Syntheses of heterocyclic compounds. DLI. Syntheses of 1-benzyl-1,2,3,4-tetrahydro-β-carboline and hexadehydroyohimbane derivatives under the condition of the Pictet-Spengler reaction. Yakugaku Zasshi 1974, 94, 261-4.
29. Onda, M.; Kawanishi, M. Analogs of Rauwolfia alkaloids. J. Pharm. Soc. Jpn. 1956, 76, 966-8.
30. Rehse, K.; Piesker, G.; Kehr, W.; Wachtel, H. Neuropsychotropic activity of the dopamine-analogous 1,2,3,4-tetrahydro-β-carbolines. Part 2. Alteration of activity by substituents. Arch. Pharm. 1979, 312 (7), 597-603.
31. Hayashi, M.; Horiguchi, A.; Kawashima, Y.; Watanabe, Y.; Hatayama, K. Preparation of tetrahydro-β-carboline derivatives as lipid peroxidation inhibitors and antiulcer agents. JP 03287586, December 18, 1991.
32. Shavel, J., Jr.; Morrison, G. C. Cis-syn-5,6,7,7a,8,8a,9,10,12,12a-decahydro-7-methyl-11H-benz[b]indolo[3,2,1-ij] [1,5]naphthyridin-11-one. US 3492304, June 24, 1968.
33. Kametani, T.; Kajiwara, M.; Fukumoto, K. Syntheses of heterocyclic compounds. DXLVII. Synthesis of a yohimban derivative by thermolysis. Tetrahedron 1974, 30, 1053-8.
34. Taborsky, R. G.; Mclsaac, W. M. Synthesis and preliminary pharmacology of some 9H-pyrido-[3,4-b]indoles (β-carbolines) and tryptamines related to serotonin and melatonin. J. Med. Chem. 1964, 7, 135-41.
35. Gaignault, J. C.; Frechet, D.; Nedelec, L. 1-Indolylmethyl)-1,2,3,4-tetrahydroisoquinolines and 1-benzyl-2,3,4,9-tetrahydro-(1H)-β-carbolines prepared from tryptamine or from its derivatives. Ann. Pharm. Fr. 1978, 36, 401-8.
36. Audia, J. E.; Droste, J. J.; Nissen, J. S.; Murdoch, G. R.; Evrard, D. A. "Pictet-Spengler-Like" Synthesis of Tetrahydro-β-carbolines Under Hydrolytic Conditions. Direct Use of aza lactones as Phenylacetaldehyde Equivalents. J. Org. Chem., in press.
37. Knabe, J.; Suggau, R. Dihydroisoquinoline rearrangement. 16. Reaction in the β-carboline series analogous to the rearrangement of1,2-dihydroisoquinolines. Arch. Pharm. 1973, 306, 500.
38. 2C receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety. Psychopharmacology 1994, 114 (1), 90-6.
39. 2C receptor blockade? Life Sci. 1994, 54, 641-4.
40. Fozard, J. R.; Kalkman, H. O. 5-Hydroxytryptamine (5HT) and the initiation of migraine: new perspectives. Naunyn-Schmiedeberg's Arch. Pharmacol. 1994, 350, 225-9.
41. Fozard, J. R. The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine? Arch. Int. Pharmacodyn. Ther. 1995, 329, 111-19.
42. Still, W. C.; Kahn, M.; Mitra, A. Rapid Chromatographic technique for preparative separations with moderate resolution. J. Org. Chem. 1978, 43, 2923-2925.
43. 1C receptor contains eight hydrophobic domains and is X-linked. Mol. Brain Res. 1991, 11, 143-149.
44. 2 serotonin receptor gene Htr-2 is tightly linked to ES-10 on mouse chromosome 14. Genomics 1991, 11, 231-234.
45. Grinnell, B. W.; Berg, D. T.; Walls, J.; Yan, B. Trans-activated expression of fully gamma-carboxylated human protein C, an antithrombotic factor. Bio/tech 1987, 5, 1189-1192.
46. Johnson, M. P.; Loncharich, R. J.; Baez, M.; Nelson, D. L. Species variations in transmembrane region V of the 5-hydroxytryptamine Type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines. Mol. Pharmacol. 1994, 45, 277-286.
47. Pazos, A.; Hoyer, D.; Palacios, J. M. Mesulergine, a selective serotonin-2 ligand in the rat cortex, does not label these receptors in porcine and human cortex: evidence for species differences in brain serotonin-2 receptors. Eur. J. Pharmacol. 1985, 106, 531-538.
48. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (Ki) and the concentratioon of an inhibitor that causes 50% inhibition (150) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
49. 15
50. 1D Receptor Agonist. J. Org. Chem. 1994, 59, 3738-41.
51. 1D Receptor Agonist. J. Org. Chem. 1994, 59, 3738-41.
52. 1D Receptor Agonist. J. Org. Chem. 1994, 59, 3738-41.
53. 1D Receptor Agonist. J. Org. Chem. 1994, 59, 3738-41.
54. 1D Receptor Agonist. J. Org. Chem. 1994, 59, 3738-41.