Novel class of potent 4-arylalkyl substituted 3-isoxazolol GABAA antagonists: Synthesis, pharmacology, and molecular modeling

Journal of Medicinal Chemistry

Volumn 45, Issue 12, 2002, Pages 2454-2468

  Frølund, Bente ^a   Jørgensen, Anne T ^a   Tagmose, Lena ^a   Stensbøl, Tine B ^a   Vestergaard, Henrik T ^a   Engblom, Christine ^a   Kristiansen, Uffe ^a   Sanchez, Connie ^b   Krogsgaard Larsen, Povl ^a   Liljefors, Tommy ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b H LUNDBECK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; 5 (4 PIPERIDYL) 3 ISOXAZOLOL 4 AMINOBUTYRIC ACID; UNCLASSIFIED DRUG;

ARTICLE; CONFORMATIONAL TRANSITION; DESENSITIZATION; DRUG POTENCY; ELECTROPHYSIOLOGY; MOLECULAR MODEL; NERVE FUNCTION; NEUROTRANSMITTER RELEASE; RECEPTOR AFFINITY; RECEPTOR BINDING; SYNTHESIS;

ANIMALS; BINDING SITES; BRAIN; CELLS, CULTURED; CONVULSANTS; EMBRYO; GABA ANTAGONISTS; ISOXAZOLES; LIGANDS; MALE; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; NEURONS; PATCH-CLAMP TECHNIQUES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPTIC MEMBRANES;

EID: 0037030612     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020027o     Document Type: Article

References (50)

1. GABA-activated ligand gated ion channels: Medicinal chemistry and molecular biology
2. Modulators of the GABA receptor. Novel therapeutic prospects
3. A receptors
4. Structure and biological activity of a series of conformationally restricted analogs of GABA
5. A new class of GABA agonist
6. Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of γ-aminobutyric acid acting as selective GABA-A antagonists
7. Neuroactive amino acids in focally epileptic human brain: A review
8. Positron emission tomography measures of benzodiazepine receptors in Huntington's disease
9. GABA and mood disorders: A brief review and hypothesis
10. GABAergic mechanisms of analgesia: An update
11. Increased GABA-A receptor binding in superficial layers of cingulate cortex in schizophrenics
12. Amino acids: Evidence for GABAergic and glutamatergic transmission abnormalities in schizophrenia
13. A receptors in schizophrenia: Studies on the human dorsolateral prefrontal cortex
14. 3H]muscimol binding sites increased in autopsied brains of chronic schizophrenics
15. Synthesis and biological activity of a GABA-A agonist which has no effect on benzodiazepine binding and structurally related glycine antagonists
16. A receptor ligand, 4-PIOL, on cultured hippocampal neurones
17. A receptor agonists. Synthesis and in vitro pharmacology of a series of nonannulated analogs of 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THIP)
18. A antagonists: Design, synthesis, and pharmacology
19. 2Et á partir du malonate acide d'éthyle
20. A safe, economical method for the preparation of β-oxo esters
21. Applications of ionic hydrogenation to organic synthesis
22. Differentiation of in vivo effects of AMPA and NMDA receptor ligands using drug discrimination methods and convulsant anticonvulsant activity
23. Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscimol and related compounds
24. Dihydromuscimol, thiomuscimol and related heterocyclic compounds as GABA analogues
25. Cation-π interactions in chemistry and biology: A new view of benzene, Phe, Tyr, and Trp
26. A receptors
27. Acetylcholine receptor channel imaged in the open state
28. Nicotinic acetylcholine receptor at 9 Å resolution
29. Synthesis and antirhinovirus activity of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substitutedbenzyl)-9H-purines
30. Naphthalene analogs of mevinolin
31. Sulfur heterocycles from the ring closure of bisarylalkyl disulfides
32. Preparation of a series of substituted fluoromethylnaphthalenes
33. Synthesis of substituted chrysenes and phenanthrenes
34. The design of radical clocks to probe the reactivity of the intermediates in arylmethyl ester photochemistry
35. 2+-entry blocking activity
36. GABA-uptake inhibitors: Construction of a general pharmacophore model and successful prediction of a new representative
37. 3H]MK-801 binding to the N-methyl-D-aspartate receptor ion channel complex by L-glutamate, glycine and polyamines
38. 3H]thiomuscimol
39. 3H] GABA into rat brain synaptosomes
40. Preparation of primary cultures of mouse cortical neurons
41. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches
42. Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones
43. MacroModel (version 6.5). An integrated software system for modeling organic and bioorganic molecules using molecular mechanics
44. An internal coordinate Monte Carlo method for searching conformational space
45. Semianalytical treatment of solvation for molecular mechanics and dynamics
46. Conformational energy penalties of protein-bound ligands
47. Assessing the distribution of parameters in models of ligand-receptor interaction: To log or not to log