Structure-activity relationships of 4-hydroxy-3-nitroquinolin-2(1H)- ones as novel antagonists at the glycine site of N-methyl-D-aspartate receptors

Journal of Medicinal Chemistry

Volumn 39, Issue 23, 1996, Pages 4682-4686

  Cai, Sui Xiong ^a   Zhou, Zhang Lin ^b   Huang, Jin Cheng ^a   Whittemore, Edward R ^a   Egbuwoku, Zizi O ^a   Hawkinson, Jon E ^a   Woodward, Richard M ^a   Weber, Eckard ^a   Keana, John F W ^b  

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

^b UNIVERSITY OF OREGON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXY 3 NITROQUINOLIN 2(1H) ONE DERIVATIVE; 5,6,7 TRICHLORO 4 HYDROXY 3 NITROQUINOLIN 2(1H) ONE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING SITE; DRUG POTENCY; INHIBITION KINETICS; NERVE EXCITABILITY; NONHUMAN; OOCYTE; RAT; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION; XENOPUS;

ANIMALS; BRAIN; GLYCINE; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; NITROQUINOLINES; RATS; RECEPTORS, AMPA; RECEPTORS, N-METHYL-D-ASPARTATE; STRUCTURE-ACTIVITY RELATIONSHIP; XENOPUS;

EID: 0001133221     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960520y     Document Type: Article

References (19)

1. Doble, A. Excitatory Amino Acid Receptors and Neurodegeneration. Therapie 1995, 50, 319-337.
2. Rothman, S. M.; Olney, J. W. Excitotoxicity and the NMDA Receptor - Still Lethal after Eight Years. Trends Neurosci. 1995, 18, 57-58.
3. Johnson, J. W.; Ascher, P. Glycine Potentiates the NMDA Response in Cultured Mouse Brain Neurons. Nature (London) 1987, 325, 529-531.
4. (a) Leeson, P. D.; Baker, R.; Carling, R. W.; Curtis, N. R.; Moore, K. W.; Williams, 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.
5. (b) Gray, N. M.; Dappen, M. S.; Cheng, B. K.; Cordi, A. A.; Biesterfeldt, J. P.; Hood, W. F.; Monahan, J. B. Novel Indole-2-carboxylates as Ligands for the Strychnine-Insensitive N-Methyl-D-aspartate-Linked Glycine Receptor. J. Med. Chem. 1991, 34, 1283-1292.
6. (c) Swartz, K. J.; Koroshetz, W. J.; Rees, A. H.; Huettner, J. E. Competitive Antagonism of Glutamate Receptor Channels by Substituted Benzazepines in Cultured Cortical Neurons. Mol. Pharmacol. 1992, 41, 1130-1141.
7. (d) Nagata, R.; Tanno, N.; Kodo, T.; Ae, N.; Yamaguchi, H.; Nishimura, T.; Antoku, F.; Tatsuno, T.; Kato, T.; Tanaka, Y.; Nakamura, M. Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor. J. Med. Chem. 1994, 37, 3956-3968.
8. (a) Kemp, J. A.; Leeson, P. D. The Glycine Site of the NMDA Receptor - Five Years on. Trends Pharmacol. Sci. 1993, 14, 20-25.
9. (b) Leeson, P. D.; Iversen, L. L. The Glycine Site on the NMDA Receptor: Structure-Activity Relationships and Therapeutic Potential. J. Med. Chem. 1994, 37, 4053-4067.
10. McQuaid, L. A.; Smith, E. C. R.; Lodge, D.; Pralong, E.; Wikel, J. H.; Calligaro, D. O.; O'Malley, P. J. 3-Phenyl-4-hydroxyquinoline-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, 3423-3425.
11. Kulagowski, J. J.; Baker, R.; Curtis, N. R.; Leeson, P. D.; Mawer, I. M.; Moseley, A. M.; Ridgill, M. P.; Rowley, M.; Stansfield, I.; Foster, A. C.; Grimwood, S.; Hill, R. G.; Kemp, J. A.; Marshall, G. R.; Saywell, K. L.; Tricklebank, M. D. 3'-(Arylmethyl)- and 3′-(Aryloxy)-3-phenyl-4-hydroxyquinoline-2(1H)-ones: Orally Active Antagonists of the Glycine Site on the NMDA Receptor. J. Med. Chem. 1994, 37, 1402-1405.
12. Rowley, M.; Leeson, P. D.; Stevenson, G. I.; Moseley, A. M.; Stansfield, I.; Sanderson, I.; Robinson, L.; Baker, R.; Kemp, J. A.; Marshall, G. R.; Foster, A. C.; Grimwood, S.; Tricklebank, M. D.; Saywell, K. L. 3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically Active Anticonvulsants Acting by Antagonism at the Glycine Site of the N-Methyl-D-aspartate Receptor Complex. J. Med. Chem. 1993, 36, 3386-3396.
13. Carling, R. W.; Leeson, P. D.; Moore, K. W.; Smith, J. D.; Moyes, C. R.; Mawer, I. M.; Thomas, S.; Chan, T.; Baker, R.; Foster, A. C.; Grimwood, S.; Kemp, J. A.; Marshall, G. R.; Tricklebank, M. D.; Saywell, Kay L. 3-Nitro-3,4-dihydro-2(1H)-quinolones. Excitatory Amino Acid Antagonists Acting at Glycine-Site NMDA and (RS)-α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors. J. Med. Chem. 1993, 36, 3397-3408.
14. Keana, J. F. W.; Kher, S. M.; Cai, S. X.; Dinsmore, C. M.; Glenn, A. G.; Guastella, J.; Huang, J. C.; Lu, Y.; Ilyin, V.; Lu, Y.; Mouser, P. L.; Woodward, R. M.; Weber, E. Synthesis and Structure-Activity Relationships of Substituted 1,4-Dihydroquinoxaline-2,3-diones (QXs): Antagonists of the Glycine Site on the NMDA Receptor and of Non-NMDA Glutamate Receptors. J. Med. Chem. 1995, 38, 4367-4379.
15. Cai, S. X.; Zhou, Z.-L.; Huang, J.-C.; Whittemore, E. R.; Egbuwoku, Z. O.; Lu, Y.; Hawkinson, J. E.; Woodward, R. M.; Weber, E.; Keana, J. F. W. Synthesis and Structure-Activity Relationships of 1,2,3,4-Tetrahydroquinoline-2,3,4-trione-3-oximes: Novel and Highly Potent Antagonists for NMDA Receptor Glycine Site. J. Med. Chem. 1996, 39, 3248-3255.
16. Buckle, D. R.; Cantello, B. C. C.; Smith, H.; Spicer, B. A. 4-Hydroxy-3-nitro-2-quinolones and Related Compounds as Inhibitors of Allergic Reactions. J. Med. Chem. 1975, 18, 726-732.
17. Leeson, P. D.; Baker, R.; Carling, R. W.; Curtis, N. R.; Moore, K. W.; Williams, 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.
18. Bigge, C. F.; Malone, T. C.; Boxer, P. A.; Nelson, C. B.; Ortwine, D. F.; Schelkun, R. M.; Retz, D. M.; Lescosky, L. J.; Borosky, S. A.; Vartanian, M. G.; Schwarz, R. D.; Campbell, G. W.; Robichaud, L. J.; Watjen, F. Synthesis of 1,4,7,8,9,10-Hexahydro-9-methyl-6-nitropyrido[3,4-f]-quinoxaline-2,3-dione and Related Quinoxalinediones: Characterization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (and N-Methyl-D-aspartate) Receptor and Anticonvulsant Activity. J. Med. Chem. 1995, 38, 3720-3740.
19. a of HNQ (8a) was estimated to be 8.5.