New esters of 4-amino-5-chloro-2-methoxybenzoic acid as potent agonists and antagonists for 5-HT4 receptors

Journal of Medicinal Chemistry

Volumn 40, Issue 4, 1997, Pages 608-621

  Yang, Donglai ^a   Soulier, Jean Louis ^a   Sicsic, Sames ^a   Mathé Allainmat, Monique ^a   Brémont, Béatrice ^a   Croci, Tiziano ^b   Cardamone, Rosanna ^b   Aureggi, Giulio ^b   Langlois, Michel ^a  

^a CNRS   (France)

^b Research Center Sanofi Midy   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 3 INDOLECARBOXYLIC ACID [1 [2 (METHYLSULFONYLAMINO)ETHYL] 4 PIPERIDINYLMETHYL] ESTER; 2,3 DIHYDRO 3 ISOPROPYL 2 OXO 1 BENZIMIDAZOLECARBOXYLIC ACID 3ALPHA TROPANYLAMIDE; 4 AMINO 5 CHLORO 2 METHOXYBENZOIC ACID 2 (1 PIPERIDINYL)ETHYL ESTER; 4 AMINO 5 CHLORO 2 METHOXYBENZOIC ACID 2 (3 HYDROXYPIPERIDINO)ETHYL ESTER; 4 AMINO 5 CHLORO 2 METHOXYBENZOIC ACID 2 (3,5 DIMETHYLPIPERIDINO)ETHYL ESTER; 4 AMINO 5 CHLORO 2 METHOXYBENZOIC ACID 2 (DIETHYLAMINO)ETHYL ESTER; 4 AMINO 5 CHLORO 2 METHOXYBENZOIC ACID 3 PIPERIDINOPROPYL ESTER; 8 AMINO 7 IODO 1,4 BENZODIOXAN 5 CARBOXYLIC ACID 1 BUTYL 4 PIPERIDINYLMETHYL ESTER; BRL 24682; METOCLOPRAMIDE; PIBOSEROD; RENZAPRIDE; SEROTONIN 4 AGONIST; SEROTONIN 4 ANTAGONIST; TRITIUM; UNCLASSIFIED DRUG; ZACOPRIDE;

ANIMAL TISSUE; ARTICLE; BINDING SITE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ESOPHAGUS MUCOSA; GUINEA PIG; ILEUM MUCOSA; LIGAND BINDING; MOLECULAR MODEL; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; GUINEA PIGS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RATS; RECEPTORS, SEROTONIN; RECEPTORS, SEROTONIN, 5-HT3; RECEPTORS, SEROTONIN, 5-HT4; SEROTONIN AGONISTS; SEROTONIN ANTAGONISTS; SOFTWARE;

EID: 0031042398     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960320m     Document Type: Article

References (68)

1. Gerald, C.; Adham, N.; Kao, H. T.; Schechter, L. E.; Olsen, M. A.; Bard, J. A.; Laz, T. M.; Vaysse, P. J. J.; Branchek, T. A.; Weinshank, R. L. The 5-HT4 receptor: molecular cloning of two splice variants. Third IUPHAR Satellite Meeting on Serotonin, Chicago, IL, July 30-Aug. 3, 1994.
2. Gerald, C.; Adham, N.; Kao, H. T.; Olsen, N. A.; Laz, T. M.; Schechter, L. E.; Bard, J. A.; Vaysse, P. J. J.; Hartig, P. R.; Branchek, T. A.; Weinshank, R. L. The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J. 1995, 14, 2806-2815.
3. (a) Dumuis, A.; Bouhelal, R.; Sebben, M.; Cory, M.; Bockaert, J. A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol. Pharmacol. 1988, 34, 880-887.
4. 4 receptors: relationship between the effects of indole, benzamide and azabicycloalkylbenzimidazolone derivatives. In Serotonin Molecular Biology, Receptors and Functional Effects; Fozard, J. R., Saxena, P. R., Eds.; Birkhäuser: Verlag, Basel, 1991; pp 220-231.
5. 4 receptor in guinea-pig ileum and rat oesophagus: role in peristalsis. In Serotonin Molecular Biology, Receptors and Functional Effects; Fozard, J. R., Saxena, P. R., Eds.; Birkhäuser: Verlag, Basel, 1991; pp 232-242.
6. 4 receptors in ascending reflexes to the circular muscle of guinea-pig small intestine. Br. J. Pharmacol. 1994, 112, 1095-1100.
7. (a) Linnik, M. D.; Butler, B. T.; Gaddis, R. R.; Ahmed, N. K. Analysis of serotoninergic mechanisms underlying benzamide-induced gastroprokinesis. J. Pharmacol. Exp. Ther. 1991, 259, 501-507.
8. 4 receptors. Eur. J. Pharmacol. 1991, 205, 203-208.
9. 4) receptors positively coupled to adenylate cyclase in adult guinea-pig hippocampal membranes: effect of substituted benzamide derivatives. Mol. Pharmacol. 1990, 37, 408-411.
10. Linnik, M. D.; Butler, B. T.; Elsea, S. H.; Ahmed, N. K. Analysis of neurogenic contractions induced by ML-1035 and other benzamides in the guinea-pig non-stimulated isolated ileum. J. Pharm. Pharmacol. 1994, 46, 491-496.
11. 4 receptor-mediated contractions. Br. J. Pharmacol. 1993, 108, 1593-1599.
12. 4 receptor in urinary bladder of Rhesus and Cynomolgus monkeys. Br. J. Pharmacol. 1994, 111, 213-218.
13. 4-like receptors. Naunyn-Schmiedeberg's Arch Pharmacol. 1990, 342, 619-622.
14. 4-like receptor in human left atrium. Naunyn-Schmiedeberg's Arch. Pharmacol. 1992, 345, 382-386.
15. 4 receptors mediate arrhythmias? Trends Pharmacol. Sci. 1994, 15, 451-455.
16. 4 receptors in the human and guinea-pig brain. NeuroReport 1993, 4, 1239-1242.
17. 4 receptor binding sites in human brain: comparaison with other mammalian species. Mol. Brain Res. 1994, 21, 176-180.
18. 4 receptors in the isolated guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol. 1992, 345, 387-393.
19. 4 receptor antagonist derived from metoclopramide. J. Med. Chem. 1993, 36, 4121-4123.
20. 4 receptor function. J. Pharm. Pharmacol. 1995, 47, 219-222.
21. 4 receptor antagonist. Naunyn-Schmiedeberg's Arch Pharmacol. 1994, 349, 546-548.
22. 4 receptors. Br. J. Pharmacol. 1993, 110, 10P.
23. 4 receptor population in piglet right atrium. Br. J. Pharmacol. 1995, 115, 933-936.
24. 4 receptor. Br. J. Pharmacol. 1994, 111, 332-338.
25. 4 receptor. 1. Design of a new class of agonists and receptor map of the agonist recognition site. J. Med. Chem. 1995, 38, 2326-2330.
26. 4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists. J. Med. Chem. 1995, 38, 2331-2338.
27. 4 receptor: Part 3: design and pharmacological evaluation of a new class of antagonists. BioMed. Chem. Lett. 1995, 5, 2495-2500.
28. 4 receptor antagonist amide with oral activity. J. Med. Chem. 1995, 38, 4760-4762.
29. 4 receptor antagonist amide with oral activity. Br. J. Pharmacol. 1996, 117, 126P.
30. Pinder, R. M.; Brogden, R. N.; Sawyer, P. R.; Speight, T. M.; Avery, G. Metoclopramide: a review of its pharmacological properties and clinical use. Drugs 1976, 12, 81-131.
31. 4 receptor agonists and gastric motility stimulants. J. Med. Chem. 1993, 36, 683-689.
32. 3 receptor antagonist. Br. J. Pharmacol. 1987, 91, 335P.
33. Imbert, T.; Dorme, N.; Langlois, M. Nouveaux dérivés de l'amino-3 quinuclidine, leur procédé de préparation et leur application en thérapeutique. European Patent 99 789.
34. 3 receptor antagonist without gastroprokinetic activity. J. Pharmacol. Exp. Ther. 1990, 254, 350-355.
35. (a) Reyntjens, A.; Verlinden, M.; Aerts, T. Development and clinical use of the new gastrointestinal prokinetic drug cisapride (RS 51619). Drug Dev. Res. 1986, 8, 251-265.
36. 4 receptors. In Mechanisms and control of emesis; Bianchi, A. L., Grélot, L., Muller, A. D., King, G. L., Eds.; Colloque INSERM, John Libbey Eurotext Ltd.: London, 1992; Vol. 223, pp 259-272.
37. Bockaert, J.; Fozard, J. R.; Dumuis, A.; Clarke, D. E. The 5-HT4 receptor: a place in the sun. Trends Pharmacol. Sci. 1992, 13, 141-145.
38. 4 receptor subtype. J. Med. Chem. 1992, 35, 1486-1489.
39. 4 receptor agonist. BioMed. Chem. Lett. 1993, 3, 633-634.
40. Langlois, M.; Yang, D.; Brémont, B.; Shen, S. Synthesis and pharmacological activity of a macrocyclic benzamide. BioMed. Chem. Lett. 1995, 5, 795-798.
41. (a) Langlois, M.; Zhang, L.; Yang, D.; Brémont, B.; Shen, S.; Manara, L.; Croci, T. Design of a potent 5-HT4 receptor agonist with nanomolar affinity. BioMed. Chem. Lett. 6999, 4, 1433-1436.
42. 4 receptor agonist. Br. J. Pharmacol. 1995, 114, 382P.
43. (a) Elz, S.; Keller, A. Alicyclic ester analogs of metoclopramide: synthesis and potent 5-HT4 antagonism on the isolated guinea-pig ileum and rat oesophagus. Arch. Pharm. 1993, 326, 671.
44. (b) Elz, S.; Keller, A. Preparation and in vitro pharmacology of 5-HT4 receptor ligands. Partial agonism and antagonism of metoclopramide analogous benzole esters. Arch. Pharm. 1995, 328, 585-594.
45. King, F. D.; Gaster, L. M.; Joiner, G. F.; Rahman, S. K.; Sanger, G. J.; Wardle, K. A.; Baxter, G. S.; Kennett, G. A.; Young, R. C.; Vimal, M.; Kaumann, A. J. International Patent Application WO 93/03725.
46. 4 receptor antagonist RS-23597 are high affinity partial agonists. BioMed. Chem. Lett. 1994, 4, 2477-2480.
47. 1H-NMR) parameters. Eur. J. Med. Chem. 1989, 24, 163-169.
48. Langlois, M.; Soulier, J. L.; Allainmat, M.; Shen, S.; Gallais, C. Derivatives of quinuclidine as 5-HT3 receptor antagonists: influence of an additional carbonyl group on the recognition of chirality by the receptor. BioMed. Chem. Lett. 1993, 3, 1555-1558.
49. (a) Langlois, M.; Croci, T.; Manara, L. Nouveaux esters de l'acide 4-amino-5-chloro-2-methoxybenzoique. French Patent 94. 02927.
50. (b) Langlois, M.; Guzzi, U.; Cecchi, R.; Croci, T. Novel 3, 5-dimethylpiperidin-1-ylalkyl esters. International Patent Application WO 95/31449.
51. Lafon, L. Dérivés de 1.4-dihydropyridine, leur procédé de préparation et composition thérapeutique les contenant. European Patent 0494816 A1.
52. 3 receptor antagonists: synthesis and pharmacological activity of various aromatic esters or amides derived from tropane and 1,2,6-trisubstituted piperidine. Eur. J. Med. Chem. 1993, 28, 869-880.
53. Grossman, C. J.; Kilpatrick, G. J.; Bunce, K. T. Development of a radioligand binding assay for 5-HT4 receptor in guinea-pig and rat brain, Br. J. Pharmacol. 1993, 109, 618-624.
54. 3 binding sites in rat brain cortical membranes. Biochem. Pharmacol. 1989, 38, 1693-1695.
55. Baxter, G. S.; Craig, D. A.; Clarke, D. E. 5-Hydroxytryptamine4 receptor mediates relaxation of the rat oesophageal tunica muscularis mucosae. Naunyn-Schmiedeberg's Arch Pharmacol. 1991, 343, 439-446.
56. (a) Arunlakshana, O.; Schild, H. O. Some quantitative uses of drug antagonists. Br. J. Pharmacol. 1959, 14, 48-57.
57. (b) Tallarida, R. J.; Murray, R. B. Manual of pharmacologic calculations with computer programs; Springer-Verlag: New York, 1987; pp 56-61.
58. 4 receptor antagonist. Br. J. Pharmacol. 1993, 110, 119-126.
59. 4 receptor mediated facilitation of the emptying phase of the peristaltic reflex in the guinea-pig isolated ileum. Br. J. Pharmacol. 1993, 110, 1572-1578.
60. 4 receptor antagonists. BioMed. Chem. Lett. 1994, 4, 2481-2484.
61. 3 receptor antagonists. Eur. J. Med. Chem. 1994, 29, 925-940.
62. 125I]iodomelatonine binding sites. J. Med. Chem. 1995, 38, 2050-2060.
63. (b) Ram, S.; Spicer, D. Debenzylation of N-benzylamine derivatives by catalytic transfer hydrogenation with ammonium formate. Synth. Commun. 1987, 17, 415-418.
64. Huang-Minlong modification of the Wolff-Kishner reduction. Vogel's Textbook of Pratical Organic Chemistry, 5th ed.; Furniss, B. S., Hannaford, A. J., Smith, P. W. G., Tatchell, A. R., Eds; Longman Scientific and Technical: Harlow, U.K.; pp 831-832.
65. Grob, C. A.; Kaiser, A.; Renk, E. 2-Dehydro-chinuclidin und 3-substituions produkte. Untersuchungen in der chinuclidin-reihe. Helv. Chem. Acta 1947, 50, 2170-2185.
66. Hall, M. D.; Gozlan, H.; Emerit, M. B.; El Mestikawi, S.; Pichat, L.; Hamon, M. Differentiation of pre- and post-synaptic high affinity serotonin receptor binding sites using physico-chemical parameters and modifiying agents. Neurochem. Res. 1986, 11, 891-912.
67. Lowry, O. H.; Rosebrough, N. J.; Fair, A. L.; Randall, R. J. Protein measurements with the folin reagent. J. Biol. Chem. 1951, 193, 265-275.
68. Bradford, M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.