Design, synthesis, SAR, and biological evaluation of highly potent benzimidazole-spaced phosphono-α-amino acid competitive NMDA antagonists of the AP-6 type

Journal of Medicinal Chemistry

Volumn 44, Issue 10, 2001, Pages 1516-1529

  Baudy, R B ^a   Fletcher III, H ^a   Yardley, J P ^a   Zaleska, M M ^a   Bramlett, D R ^a   Tasse, R P ^a   Kowal, D M ^a   Katz, A H ^a   Moyer, J A ^a   Abou Gharbia, M ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 (5 CHLORO 1 PHOSPHONOMETHYL 1H BENZOIMIDAZOL 2 YL)PROPIONIC ACID; 2 AMINO 4,5 (1,2 CYCLOHEXYL) 7 PHOSPHONOHEPTANOIC ACID; 2 AMINO 5 PHOSPHONOVALERIC ACID; 2 AMINO 7 PHOSPHONOHEPTANOIC ACID; 4 PHOSPHONOMETHYLPIPECOLIC ACID; AP 6; BENZIMIDAZOLE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PHOSPHONOAMINO ACID; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN INFARCTION; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG DETERMINATION; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; LETHALITY; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; RAT; RECEPTOR BLOCKING; SEIZURE; STRUCTURE ACTIVITY RELATION;

ANIMALS; ARTERIAL OCCLUSIVE DISEASES; BENZIMIDAZOLES; BINDING, COMPETITIVE; BRAIN; CAROTID ARTERY DISEASES; DRUG EVALUATION, PRECLINICAL; EXCITATORY AMINO ACID ANTAGONISTS; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; MICE; MODELS, MOLECULAR; NEUROPROTECTIVE AGENTS; PROPIONIC ACIDS; RADIOLIGAND ASSAY; RATS; RATS, INBRED F344; RECEPTORS, N-METHYL-D-ASPARTATE; STEREOISOMERISM;

EID: 0035837062     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000385w     Document Type: Article

References (38)

1. The excitation and depression of mammalian cortical neurones by amino acids
2. Cytotoxic effect of acidic and sulphur-containing amino acids on the infant mouse central nervous system
3. The toxic effect of sodium L-glutamate on the inner layers of the retina
4. Neurotoxic action of kainic acid
5. The excitatoxic hypothesis in relation to cerebral ischemia
6. The role of excitatory amino acids and NMDA receptors in traumatic brain injury
7. Cerebral ischemia: Some new approaches and unanswered questions
8. Head injury treatment in evolution. Pharmacologic therapy for traumatic brain injury. Experimental approaches
9. Introducing NMDA antagonists into clinical practice; Why head injury trials?
10. Mechanisms of disease. Excitatory amino acids as a final common pathway for neurologic disorders
11. Contributory mechanisms in the causation of neurodegenerative disorders
12. A revived target for drug development? Glutamate in CNS disorders
13. Glutamate antagonists as novel neuroprotective agents
14. Clinical experience with excitatory amino acid antagonist drugs
15. Potent quinoxaline-spaced phosphono-α-amino acids of the AP-6 type as competitive NMDA antagonists: Synthesis and biological evaluation
16. Design and synthesis of [2-(8,9-dioxo-2,6-diazabicyclo [5.2.0]non1(7)-en-2-yl)ethyl] phosphonic acid (EAA-090), a potent N-methyl-D-aspartate antagonist, via the use of 3-cyclobutene-1,2-dione as an achiral α-amino acid bioisostere
17. Synthesis of peptides with mixed anhydrides
18. Synthesis of a novel class of heteroaromatic amino acids and their use in the preparation of analogues of luteinizing hormone-releasing hormone
19. Interhalogen-catalyzed cleavages of ethers and esters with trimethylsilyl bromide or chloride
20. Geminal acylation-alkylation at a carbonyl center using diethyl-N-benzylideneaminomethyl phosphonate: Preparation of 2-methyl-2-phenyl-4-pentenal
21. Single-step conversion reactions of nitro aromatic compounds to amino compounds
22. A new reagent for activating carboxyl groups: Preparation and reactions of N,N-bis[2-oxo-3-ox-azolidinyl]phosphoro diamidic chloride
23. Cleavage of N-carbobenzoxy groups by dry hydrogen bromide and hydrogen chloride
24. Trimethylsilyl iodide as a peptide deblocking Agent
25. Kinetic characterization of the phencyclidine-N-methyl-D-aspartate receptor interaction: Evidence for a steric blockade of the channel
26. Excitatory amino acid receptors in the brain, membrane binding and receptor autoradiographic approaches
27. Ifenprodil and SL82.0715 as cerebral anti-ischemic agents. II. Evidence for N-methyl-D-aspartate receptor antagonist properties
28. Animal models for the study of drugs in ischemic stroke
29. Analytical methods for the investigation of the transport of natural and synthetic glycine site NMDA receptor antagonists across the blood-brain barrier
30. Aromatic fluorine compounds, VIII. Plant growth regulators and intermediates
31. Binding of [3H] 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to rat brain membranes: A selective, high-affinity ligand for N-methyl-D-aspartate receptors
32. 4-(Posphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids: Synthesis, activity at N-methyl-D-aspartic acid receptors, and anticonvulsant activity
33. Focal brain ischemia in the rat: Method for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral artery and ipsilateral common carotid arteries