(E)-3-(2-(N-phenylcarbamoyl)vinyl)pyrrole-2-carboxylic acid derivatives. A novel class of glycine site antagonists

Journal of Medicinal Chemistry

Volumn 41, Issue 6, 1998, Pages 808-820

  Balsamini, Cesarino ^a,b   Bedini, Annalida ^a  

^a UNIVERSITY OF URBINO   (Italy)

^b GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 BROMO 5 METHYL 3 [2 (N PHENYLCARBAMOYL)VINYL]PYRROLE 2 CARBOXYLIC ACID; 4,5 DIBROMO 3 [2 (N PHENYLCARBAMOYL)VINYL]PYRROLE 2 CARBOXYLIC ACID; 4,5 DIMETHYL 3 [2 (N PHENYLCARBAMOYL)VINYL]PYRROLE 2 CARBOXYLIC ACID; CARBOXYLIC ACID; CARBOXYLIC ACID DERIVATIVE; GLYCINE RECEPTOR ANTAGONIST; N METHYL DEXTRO ASPARTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; STRYCHNINE; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; BINDING SITE; CONVULSION; DRUG BINDING; DRUG POTENCY; DRUG SYNTHESIS; INTRAVENOUS DRUG ADMINISTRATION; LIPOPHILICITY; MALE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ACRYLAMIDES; ANIMALS; ANTICONVULSANTS; CEREBRAL CORTEX; GLYCINE AGENTS; INDOLES; MICE; MODELS, MOLECULAR; N-METHYLASPARTATE; PYRROLES; RATS; RECEPTORS, GLYCINE; RECEPTORS, N-METHYL-D-ASPARTATE; SEIZURES; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPSES;

EID: 15644370222     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970416w     Document Type: Article

References (64)

1. Choi, D. W.; Rothman, S. M. The Role of Glutamate Neurotoxicity in Hypoxic-Ischaemic Neuronal Death. Annu. Rev. Pharmacol. Toxicol. 1991, 31, 171-82.
2. (a) Choi, D. W. Cerebral Hypoxia: Some New Approaches and Unanswered Questions. J. Neurosci. 1990, 10, 2493-2501.
3. (b) Meldrum, B. Protection Against Ischaemic Neuronal Damage by Drugs Acting on Excitatory Neurotransmission. Cerebrovasc. Brain Metab. Rev. 1990,2, 27-57.
4. McCullough, J. Excitatory Amino Acids Antagonists and Their Potential for the Treatment of Ischaemic Brain Damage in Man. Br. J. Clin. Pharmacol. 1992, 34, 106-114.
5. (a) Cotman, C. W.; Foster, A. C.; Lanthorn, T. H. An overview of glutamate as a neurotransmitter. Adv. Biochem. Biopharmacol. 1981,27, l-27.
6. (b) Watchins, J. C.; Evans, R. H. Excitatory Amino Acids Transmitters Annu. Rev. Pharmacol. Toxicol. 1981, 21, 165-204.
7. Olney, J. W. Excitotoxic amino acids and neuropsychiatrie disorders. Annu. Rev. Pharmacol. Toxicol. 1990, 30, 47-71.
8. Rothman, S. M.; Olney, J. W. Excitotoxicity and the NMDA receptor. Trends Neurosci. 1987, 10, 299-302.
9. Meldrum, B.; Garthwaite, J. Excitatory amino acid neurotoxipity and neurodegenerative disease. Trends Pharmacol. Sei. 1990, 11, 379-387.
10. Lipton, S. A.; Rosemberg, P. A. Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med. 1994, 330, 613-622.
11. (a) Johnson, J. W.; Ascher, P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 1987, 325, 529-531.
12. (b) Kleckner, N. W.; Dingledine, R. Requirements for Glycine in Activation of NMDA Receptors Expressed in Xenopus Oocytes. Science 1988,241, 835-37
13. Thomson, A. M. Glycine is a Coagonist at the NMDA Receptor/Ion Channel Complex. Progr. Neurobiol. 1990,35, 53-74.
14. Huettner, J. E. Competitive Antagonism of Glycine at the N-Methyl-D-Aspartate (NMDA) Receptor. Biochem. Pharmacol. 1991, 41, 9-16.
15. (a) Leeson, P. D.; Iversen, L. L. The glycine site on the NMDA receptor: structure-activity relationship and therapeutic potential. J. Med. Chem. 1994,37, 4053-4067.
16. (b) Iversen, L. L.; Kemp, J. A. Non Competitive NMDA Antagonists as Drugs. In The NMDA Receptor, 2nd ed.; Collingridge, G. L., Watkins, J. C., Eds.; IRL Press: Oxford, England, 1994; Chapter 20, pp 469-486.
17. Kulagowski, J. J.; Leeson, P. D. Glycine-site NMDA Receptor Antagonists. Exp. Opin. Ther.Pat. 1995,5,1061-1075.
18. Kulagowski, J. J. Glycine-site NMDA Receptor Antagonists: An Update. Exp. Opin. Ther. Pat. 1996, 6, 1069-1079.
19. (e) Di Fabio, R.; Gaviraghi, G.; Reggiani, A. Strychnine-Insensitive Glycine Binding Site and the NMDA Receptor. Chim. Ind. 1996, 78, 283-289.
20. (f) The model in Figure 2 is an adaptation of the original model described in ref 9a. Compound 6w was superimposed to it using the active analogue approach implemented with Sybyl 6.0 software (TRIPOS Inc., St.Louis, MO) as described in ref 18b for GV150526A and analogues.
21. Leeson, P. D.; Baker, R.; Carling, R. W.; Curtis, N. R.; Moore, K. W.; William, B. J.; Foster, A. C.; Donald, A. E.; Kemp, J A.; Marshall, G. R. Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor. J. Med. Chem. 1991,34, 1243-1252.
22. Leeson, P. D.; Carling, R. W.; Moore, K. W.; Moseley, A. M.; Smith, G. D.; Stevenson, G.; Chan, T.; Baker, R.; Foster, A. C.; Grimwood, S.; Kemp, G. A.; Marshall, G. R.; Hoogsteen, K. 4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor. J. Med. Chem. 1992, 35, 1954-1968.
23. Carling, R. W.; Leeson, P. D.; Moseley, A. M.; Smith, J. D.; Saywell, K.; Triclebank, M. D.; Kemp, J. A.; Marshall, G. R.; Foster, A. G.; Grimwood, S. Anticonvulsant activity of glycinesite NMDA antagonists. 2. trans-2-Carboxy-4-substituted tetrahydroquinolines. Bioorg. Med. Chem. Lett. 1993, 3, 65-70.
24. Salituro, F. G.; Harrison, B. L.; Baron, B. M.; Nyce, P. L.; Stewart, K. T.; Kehne, J. H.; White, H. S.; McDonald, I. A. 3-(2-Carboxyindol-3-yl)propionic acid-based antagonists of the Nmethyl-D-aspartic acid receptor associated glycine binding site. J. Med. Chem. 1992, 35, 1791-1799.
25. McQuaid, L. A.; Smith, E. C. R.; Lodge, D.; Pralong, E.; Wikel, J. H.; Calligaro, D. O.; O'Malley, P. J. 3-Phenyl-4-hydroxyquinolin-2(1H)-ones: potent and selective antagonists at the strychnine-insensitive glycine site on the N-methyl-D-aspartate receptor complex. J. Med. Chem. 1992, 35, 3623-3625.
26. Kulagowski, J. J.; Baker, R.; Curtis, N. R.; Leeson, P. D.; Mawer, I. M.; Moseley, A. M.; Ridgill, M. P.; Rowley, M.; Stanfield, I.; Foster, A. C.; Grimwood, A. G.; Hill, R. G.; Kemp, J. A.; Marshall, G, R.; Saywell, K. L.; Tricklebank, M. D. 3'-(Arylmethyl)- and 3′-(Aryloxy)-3-phenyI-4-hydroxyquinolin-2(lH)-ones: Orally Active Antagonists of the Glycine Site on the NMDA Receptor. J. Med. Chem. 1994, 37, 1402-1405.
27. Swartz, K. J.; Koroshetz, W. J.; Ress, A. H.; Heuttner, J. E. Competitive antagonism of glutamate receptor channels by substituted benzazepines in cultured cortical neurons. Mol. Pharmacol. 1992, 41, 1130-1141.
28. Brennan, M. B. Stroke drugs send researchers back to the drawing board. Chem. Eng. News 1996, May 13th, 41-45.
29. (a) Di Fabio, R.; Cugola, A.; Donati, D.; Feriani, A.; Gaviraghi, G.; Ratti, E.; Trist, D.; Reggiani, A. Novel substituted indole-2-carboxylates as potent glycine antagonists. 21st ACS National Meeting, New Orleans, LA, March 24-28, 1996, Abstract Medi 107.
30. (b) Di Fabio, R.; Capelli, A. M.; Conti, N.; Cugola, A.; Donati, D.; Feriani, A.; Gastaldi, P.; Gaviraghi, G.; Hewkin, T.; Micheli, F.; Missio, A.; Mugnaini, M.; Pecunioso, A.; Quaglia, A. M.; Ratti, E.; Rossi, L.; Tedesco, G.; Trist, D. G.; Reggiani, A. Substituted Indole-2-carboxylates as in vivo Potent Antagonists at the Stychnine-Insensitive Glycine Binding Site. J. Med. Chem. 1997, 40, 841-850.
31. Mawer, I. M.; Kulagowski, J. J.; Leeson, P. D.; Grimwood, S.; Marshall, G. Tetramic acids as novel glycine site antagonists. Bioorg. Med. Chem. Lett. 1995, 5, 2643-2648.
32. Hose, W.; Nickisch, K.; Bohlmann, F. Synthese von 5,7a-Bidehydroheliotridin-3-on, dem grundkorper einer neuen Gruppe von Pyrrolizidin-alkaloiden. (Synthesis of 5,7a-didehydroheliotridin-3-one, the parent compound of a new class of pyrrolizidine alkaloids.) Chem. Ber. 1980, 113, 2694-8.
33. Hemetsberger, H.; Spira, T.; Schonfelder, W. Synthese und Thermolyse von α-Azidodienestem. (Synthesis and thermolysis of α-azido-α.γ-dienoic esters.) J. Chem. Res. Miniprint 1977, 2701-2719.
34. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W.; Sikorski, J. A. Application of 2-substituted vinylamidinium salts to the synthesis of 2,4-disubstituted pyrroles. J. Org. Chem. 1990, 55, 4735-4740.
35. Balsamini, C.; Bedini, A.; Tarzia, G.; Tontini, A. An improved route to cycloalka[b]pyrrole 2-carboxylates. Org. Prep. Proced. Int. 1997,29, 471-473.
36. Crook, P. J.; Jackson, A. H.; Kenner, G. W. Synthese von α-oximesoporphyrin-IX. (Pyrroles and related compounds. XVIII. Synthesis of α-oxymesoporphyrin-IX) Liebigs Ann. Chem. 1971, 748, 26-37.
37. Fischer, H.; Fink, E. A new synthesis of pyrroles. Z. Physiol. Chem. 1948, 283, 152-161.
38. Huisgen, R.; Laschtuvka, E. A new synthesis of derivatives of pyrrole. Chem Ber. 1960, 93, 65-81.
39. Clezy, P. S.; Le Van Phuc; Prashar, J. K. The chemistry of pyrrolic compounds. LXVI The synthesis of two petroporphyrins substituted with a fused five-membered ring system: examples of possible chlorophyll C involvement in petroporphyrin formation. Aust. J. Chem. 1991, 44, 1061-1075.
40. Boukou-Poba, J. P.; Farmer, M.; Guilard, R. A general method for the synthesis of 2-arylpyrroles. Tetrahedron Lett. 1979, 1717-1720.
41. Padwa, A.; Gasdaska, J. R.; Tomas, M.; Turro, N. J.; Cha, Y.; Gould, I. R. Carbene and silicon routes as methods for the generation and dipolar cycloaddition reactions of methyl nitrile ylide. J. Am. Chem. Soc. 1986, 108, 6739-6746.
42. Kloog, Y.; Haring, R.; Sokolovski, M. Kinetic Characterization of the Phenylcyclidine-Af-Methyl-D-Aspartate Receptor Interaction: Evidence For Steric Blockade of the Channel. Biochemistry 1988, 27, 843-48.
43. Skagerberg, B.; Bonelli, D.; Clementi, S.; Cruciani, G.; Ebert, C. Principal properties for aromatic substituents. A multivariate approach for design in QSAR. Quant. Struct-Act. Relat. 1989, 8, 32-38
44. Hansch, C.; Leo, A. Substituent constants for Correlation Analysis in Chemistry and Biology; John Wiley & Sons: New York, 1979
45. Wold, S.; Albano, C.; Dunn, W. J., HI; Edlund, U.; Esbensen, K; Geladi, P.; Hellberg S.; Johansson, E.; Linberg, W.; Sjöström M. In Chemometrics; Kowalski, B. R. (Ed.) Reidel: Dordrecht 138, 17 1984.
46. (a) Baroni, M.; Costantino, G.; Cruciani, G.; Riganelli, D.; Valigi, R.; Clementi, S. Generating Optimal Linear PLS Estimations (GOLPE): an Advanced Chemometric Tool for Handling 3DQSAR Problems. Quant. Struc.-Act. Relat. 1993, 12, 9-20.
47. (b) Golpe 3.0, MIA, 1996
48. (a) Wold, S.' Cross-Validatory Estimation of the Number of Components in Factor and Principal Components Models. Technometrics 1978,20, 397-405.
49. (b) In general the native Hansch variables, provided that the correlation among them is low, give a more detailed description with respect to PPs, in which many different effects are compressed in the same variable.
50. Wold, S. Validation of QSARs. Quant. Struc.-Act. Relat. 1991, 10, 191-193.
51. Rowley, M.; Leeson, P.; Grimwood, S.; Marshall, G.; Saywell, K. 5,6,7,8-Tetrahydroquinolones as antagonists at the glycine site of the NMDA receptor. Bioorg. Med. Chem. Lett. 1995, 5, 2089-2092.
52. von Miller, W.; Kinkelin, Fr. Über eine neue Reihe von Chinolinderivate. (A new series of quinoline derivatives.) Chem. Ber. 1886, 19, 525-535.
53. Curtius, Th.; Havehn, W. Action of esters of azido fatty acids and of carbamic azide upon esters of acetylenedicarboxylic acid. J. Prakt. Chem. 1930, 125, 498-523.
54. Schorigin, P.; Issaguljanz, W.; Matschinskaja, I. Aldehyde von Typus des Zimtaldehyds, II. Mitteil.: α-Phenyl- und α-Benzylzimtaldehyd. (Aldehydes of the type of cinnamaldehyde II.; α-phenyl- and α-benzyl-cinnamaldehyde.) Chem. Ber. 1933, 66, 389-393.
55. Sonnet, P. E. Synthesis of the Trail Marker of the Texas LeafCutting Ant, Atta texana (Buckley). J. Med. Chem. 1972,15,97-98.
56. Kishimoto, H.; Simon.J. R.; Aprison, M. H. Determination of the Equilibrium Dissociation Constants at a Number of Glycine Binding Sites In Several Areas of the Rat Central Nervous System, Using a Na-Independent System. J. Neurochem. 1981, 37, 1015-1024.
57. Mumson, P. D.; Rodbard, D. LIGAND: a Versatile Computerized Approach for Characterization of Ligand-binding Data. Anal. -. Biochem., 1980, 707, 220-39.
58. van Amsterdam, F. Th. M.; Giberti, A.; Mugnaini, M.; Ratti, E. 3-[(±)-2-Carboxypiperazin-4-yl]propyl-l-Phosphonic Acid Recognizes Two AT-Methyl-D-Aspartate Binding Sites in Rat Cerebral Cortex Membranes. J. Neurochem. 1992, 59, 1850-55.
59. 3H]-α-Amino-3-Hydroxy-5-Methyl-Isoxazole-4-Propionic Acid (AMPA) to Rat Cortex Membranes Reveals Two Sites of Affinity States. J. Recept. Res. 1991, 11, 727-41.
60. 3H]-Kainate Binding Sites with DifTerent Molecular Target Sizes in Rat Cortex. Neurosci. Lett. 1986, 65, 47-52.
61. Ratti, E.; Tacconi, S.; Graziani, F.; Gaviraghi, G. Requirements of the Glycine for the Glutamate Activity at the NMDA Receptor Site. Eur. J. Pharmacol. 1990, 183, 1665.
62. Chiamulera, C.; Costa, S.; Reggiani, A. Effect of NMDA and strychnine-insensitive glycine site antagonist on NMDA-mediated convulsions and learning. Psycopharmacology 1990, 112, 551-552.
63. Daylight v4.41, Daylight Chemical Information Systems, 1995.
64. a Predictions for Organic Acids and Bases; Chapman and Hall Ltd.: London, 1981.