Structure-activity relationships for a series of bis(phenylalkyl)amines: Potent subtype-selective inhibitors of N-methyl-D-aspartate receptors

Journal of Medicinal Chemistry

Volumn 41, Issue 18, 1998, Pages 3499-3506

  Tamiz, Amir P ^a   Whittemore, Edward R ^b   Zhou, Zhang Lin ^b   Huang, Jin Cheng ^b   Drewe, John A ^b   Chen, Jie Cheng ^b   Cai, Sui Xiong ^b   Weber, Eckard ^b   Woodward, Richard M ^b   Keana, John F W ^a  

^a UNIVERSITY OF OREGON   (United States)

^b Department of Pharmacokinetics and Drug Metabolism   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 BENZYL ALPHA (4 HYDROXYPHENYL) BETA METHYL 1 PIPERIDINEPROPANOL; BUPHENINE; CP 101 606; ELIPRODIL; IFENPRODIL; N [2 (4 HYDROXYPHENYL)ETHYL] 5 PHENYLPENTYLAMINE; NYLINDRIN; PHENYLALKYLAMINE; RECEPTOR SUBUNIT; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BRAIN PROTECTION; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; NONHUMAN; PARKINSON DISEASE; XENOPUS;

ANIMALS; BUTYLAMINES; EXCITATORY AMINO ACID ANTAGONISTS; NYLIDRIN; OOCYTES; PHENOLS; RATS; RECEPTORS, N-METHYL-D-ASPARTATE; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; XENOPUS LAEVIS;

EID: 15644370726     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980235+     Document Type: Article

References (29)

1. (a) McCulloch, J. Excitatory Amino Acid Antagonists and their Potential for the Treatment of Ischeamic Brain Damage in Man. Br. J. Clin. Pharamcol. 1992, 34, 106-114.
2. (b) Rogawski, M. A. The NMDA Receptor, NMDA Antagonists and Epilepsy Therapy. Drugs 1992, 44, 279-292.
3. (c) Wilcox, G. L. Excitatory Neurotransmitters and Pain. In Proceedings of the VI World Congress on Pain; Bond, M. R., Charlton, J. E., Woolf, C. J., Eds.; Elsevier Science Publishers: Amsterdam, 1992; pp 97-117.
4. (d) Starr, M. S. Antiparkinsonian Actions of Glutamate Antagonists - alone and with L-DOPA: a Review of Evidence and Suggestions for Possible Mechanisms. J. Neural. Transm. [P-D Sect.] 1995, 10, 141-185.
5. (a) Olney, J. W.; Labruyere, J.; Price, M. T. Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs. Science (Washington D.C.) 1989, 244, 1360-1362.
6. (b) Willetts, J.; Balster, R. L. The Discriminative Stimulus Effects of N-methyl-D-aspartate Antagonists in Phencyclidine-trained Rats. Neuropharmacology 1988, 27, 1249-1256.
7. (c) Tricklebank, M. D.; Singh, L.; Oles, R. J.; Preston, C.; Iversen, S. D. The Behavioral Effects of MK-801: a Comparison With Antagonists Acting Noncompetitively and Competitively at the NMDA Receptor. Eur. J. Pharmacol. 1989, 167, 127-135.
8. (a) Moriyoshi, K. M.; Masu, M.; Ishii, T.; Shigemoto, R.; Mizuno, N.; Nakanishi, S. Molecular Cloning and Characterization of the Rat NMDA Receptor. Nature (London) 1991, 354, 31-37.
9. (b) Sugihara, H.; Moriyoshi, K.; Ishii, T.; Masu, M.; Nakanishi, S. Structures and Properties of Seven Isoforms of NMDA Receptor Generated by Alternative Splicing. Biochem. Biophys. Res. Commun. 1992, 185, 826-832.
10. (c) Monyer, H.; Sprengel, R.; Schoepfer, R.; Herb, A.; Higuchi, M.; Lomeli, H.; Burnashev, N.; Sakmann, B.; Seeburg, P. H. Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes. Science (Washington D.C.) 1992, 256, 1217-1221.
11. Monyer, H.; Burnashev, N.; Laurie, D. J.; Sakmann, B.; Seeburg, P. H. Developmental and Regional Expression in the Rat Brain and Functional Properties of Four NMDA Receptors. Neuron 1994, 12, 529-534.
12. Williams, K.; Russell, S. L.; Shen, Y. M.; Molinoff, P. B. Developmental Switch in the Expression of NMDA Receptors Occurs in vivo and in vitro. Neuron 1993, 10, 267-278.
13. (b) Williams, K. Ifenprodil Discriminates Subtypes of the N-methyl-D-aspartate Receptor: Selectivity and Mechanisms at Recombinant Heteromeric Receptors. Mol. Pharmacol. 1993, 44, 851-859.
14. Scatton, B.; Avenet, P.; Benavides, J.; Carter, C.; Duverger, D.; Oblin, A.; Perrault, G.; Sanger, D. J.; Schoemaker, H. Neuroprotective Potential of the Polyamine Site-directed NMDA Receptor Antagonists - Ifenprodil and Eliprodil. In Direct and Allosteric Control of Glutamate Receptors; Palfreyman, M. G., Reynolds, I. J., Skolnick, P., Eds.; CRC Press: Boca Raton, FL, 1994; p 139.
15. (a) Chenard, B. L.; Bordner, J.; Butler, T. W.; Chambers, L. K.; Collins, M. A.; De Costa, D. L.; Ducat, M. F.; Dumont, M. L.; Fox, C. B.; Mena, E. E.; Meniti, F. S.; Nielsen, J.; Pagnozzi, M. J.; Richter, K. E. G.; Ronau, R. T.; Shalaby, I. A.; Stemple, J. Z.; White, W. F. (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: a Potent New Neuroprotectant which Blocks N-methyl-D-aspartate Responses. J. Med. Chem. 1995, 38, 3138-3145.
16. (b) Mott, D.; Zhang, D. S.; Washburn, M. S.; Fendley, M.; Dingledine, R. CP-101,606 Antagonizes NMDA Receptors by Interacting with the Polyamine Modulatory Site. Soc. Neurosci. Abstr. 1996, 22, 66.
17. Fischer, G.; Mutel, V.; Trube, G.; Malherbe, P.; Kew, J. N. C.; Mohacsi, E.; Heitz, M. P. Kemp, J. A. Ro 25-6981, a Highly Potent and Selective Blocker of N-Methyl-D-aspartate Receptors Containing the NR2B Subunit. Characterization in vitro. J. P. E. T. 1997, 283, 1285-1293.
18. (a) Fletcher, E. J.; MacDonald, J. F. Haloperidol Interacts with the Strychnine-Insensitive Glycine Site at the NMDA Receptor in Cultured Mouse Hippocampal Neurones. Eur. J. Pharmacol. 1993, 235, 291-295.
19. (b) Ilyin, V. I.; Whittemore, E. R.; Guastella, J.; Weber, E.; Woodward, R. M. Subtype-Selective Inhibition of N-methyl-D-aspartate Receptors by Haloperidol. Mol. Pharmacol. 1996, 50, 1541-1550.
20. (c) Coughenour, L. L.; Cordon, J. J. Characterization of Haloperidol and Trifluperidol as Subtype-Selective N-methyl-D-aspartate (NMDA) Receptor Antagonists Using [3H]TCP and [3H]Ifenprodil Binding in Rat Brain Membranes. J. Pharmacol. Exp. Ther. 1997, 280, 584-592.
21. Whittemore, E. R.; Ilyin, V. I.; Woodward, R. M. Antagonism of N-methyl-D-aspartate Receptors by a (Sigma) Site Ligands: Potency, Subtype-Selectivity, and Mechanisms of Inhibition. J. Pharmacol. Exp. Ther. 1997, 282, 326-338.
22. (a) Legendre, P.; Westbrook, G. L. Ifenprodil Blocks N-methyl-D-aspartate Receptors by a Two-Component Mechanism. Mol. Pharmacol. 1991, 40 (2), 289-298.
23. (b) Kew, J. N. C.; Trube, G.; Kemp, J. A. A Novel Mechanism of Activity-Dependent NMDA Receptor Antagonism Describes the Effect to Ifenprodil in Rat Cultured Cortical Neurons. J. Physiol. (Cambridge, U.K.) 1996, 497 (3), 761-772.
24. (a) Whittemore, E. R.; Ilyin, V. I.; Konkoy, C. S.; Woodward, R. M. Subtype-Selective Antagonism of NMDA Receptors by Nylidrin. Eur. J. Pharm. 1997, 337, 197-208.
25. 2N· HCl. Cryst. Struct. Commun. 1981, 10, 1365-1368. (The nomenclature for nylidrin given in the title of this paper is not correct.)
26. (a) Mahin, P. J. Substituted Phenoxyaminopropanol Derivatives, Intermediates and Medicament Containing them. Eur. Pat. Appl. EP 81-101321, 1981.
27. (b) Subbarao, K. V.; Damodaran, N. P.; Dev, S. Photochemical Transformations. Part 4. Solution Chemistry of 4-Phenyl-1-iodobutane and 4-Phenyl-1-bromobutane. Tetrahedron 1987, 43, 2543-2548.
28. (c) Cativiela, C.; Serrano, J. L.; Zurbano, M. M. Synthesis of 3-Substituted Pentane-2,4-Diones: Valuable Intermediates for Liquid Crystals. J. Org. Chem. 1995, 60, 3074-3083.
29. Zar, J. H. Biostatistical Analysis; Prentice-Hall: Englewood Cliffs, NJ, 1974; p 620.