Synthesis of novel γ-aminobutyric acid (GABA) uptake inhibitors. 5.1 Preparation and structure - Activity studies of tricyclic analogues of known GABA uptake inhibitors

Journal of Medicinal Chemistry

Volumn 44, Issue 13, 2001, Pages 2152-2163

  Andersen, K E ^a   Sorensen J L ^a   Lau, J ^a   Lundt, B F ^a   Petersen, H ^a,b   Huusfeldt, P O ^a   Suzdak, P D ^a,c   Swedberg, M D B ^a,d  

^a NOVO NORDISK A S   (Denmark)

^b H LUNDBECK A S   (Denmark)

^c GUILFORD PHARMACEUTICALS INC   (United States)

^d ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4,4 DIPHENYL 3 BUTENYL)NIPECOTIC ACID; 1 [2 [4,4' BIS(TRIFLUOROMETHYL)BENZHYDRYLOXY]ETHYL] 1,2,5,6 TETRAHYDRO 3 PYRIDINECARBOXYLIC ACID; 4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; 4 ETHYL 6,7 DIMETHOXY BETA CARBOLINE 3 CARBOXYLIC ACID METHYL ESTER; [2 [2 (10,11 DIHYDRO 5H DIBENZ[B,F]AZEPIN 5 YL)ETHOXY]ETHYL] 3 PIPERIDINECARBOXYLIC ACID; AMINO ACID; AMITRIPTYLINE; ANTICONVULSIVE AGENT; CARBOXYLIC ACID DERIVATIVE; DESIPRAMINE; GUVACINE DERIVATIVE; NIPECOTIC ACID DERIVATIVE; NITROGEN; TIAGABINE; TRICYCLIC ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG;

4 AMINOBUTYRIC ACID UPTAKE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CLONIC SEIZURE; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; LIPOPHILICITY; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; SYNAPTOSOME;

ANIMALS; ANTICONVULSANTS; ANTIDEPRESSIVE AGENTS, TRICYCLIC; BRAIN CHEMISTRY; CARBOLINES; CONVULSANTS; FEMALE; GAMMA-AMINOBUTYRIC ACID; MICE; MUSCULOSKELETAL EQUILIBRIUM; NEUROGLIA; NEURONS; NEUROTRANSMITTER UPTAKE INHIBITORS; RATS; SEIZURES; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPTOSOMES;

EID: 0035927433     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990513k     Document Type: Article

References (81)

1. Synthesis of novel GABA uptake inhibitors. 4. Bioisosteric transformation and successive optimisation of known GABA uptake inhibitors leading to a series of potent anticonvulsant drug candidates
2. Biochemical and electrophysiological characteristics of mammalian GABA receptors
3. Biochemistry, anatomy, and pharmacology of GABA neurons
4. Biochemistry, anatomy, and pharmacology of GABA neurons
5. GABA synaptic mechanisms: Stereochemical and conformational requirements
6. GABAmimetics in animal models of seizure states
7. GABA
8. Plasma GABA: A possible indicator of altered GABA functions in psychiatric illness
9. Inhibitory, GABAergic nerve terminals decrease in sites of focal epilepsy
10. Studies on γ-aminobutyric acid transport in cobalt experimental epilepsy in the rat
11. γ-aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects
12. Recent advances in GABA agonists, antagonists and uptake inhibitors: Structure-activity relationships and therapeutic potential
13. Vigabatrin
14. Vigabatrin: A new anti-epileptic
15. GABA uptake inhibitors; Relevance to antiepileptic drug research
16. Effects of THIP on chronic anxiety
17. Design, synthesis, and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: Identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3
18. Tiagabine, SK&F 89976A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1
19. GABA uptake inhibitors as experimental tools and potential drugs in epilepsy research
20. GABA agonists and uptake inhibitors. Synthesis, absolute stereochemistry, and enantioselectivity of (R)-(-)- and (S)-(+)-Homo-β-proline
21. Systematic study of GABA analogues of restricted conformation
22. Blood-brain barrier: Techniques for the intracerebral administration of drugs
23. Problems of delivery of drugs to the brain
24. Novel inhibitors of γ-amino-butyric acid (GABA) uptake: Anticonvulsant actions in rats and mice
25. Modulation of GABA receptor interaction with GABA uptake inhibitors
26. (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain γ-aminobutyric acid uptake carrier
27. Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor
28. Anticonvulsant action in the epileptic gerbil of novel inhibitors of GABA uptake
29. Orally active and potent inhibitors of gamma aminobutyric acid uptake
30. Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations
31. Prophylaxis of amygdala-kindling induced epileptogenesis: Comparison of a GABA uptake inhibitor and diazepam
32. Structure - Activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake
33. Synthesis and metabolic profile of CI-966: A potent, orally-active inhibitor of GABA uptake
34. GABA uptake inhibitors containing mono- and diarylmethoxyalkyl N-substituents
35. Pharmacology of CI-966: A potent GABA uptake inhibitor, in vitro and in experimental animals
36. GABA uptake inhibitors. Construction of a general pharmacophore model and successful prediction of a new representative
37. GABA uptake inhibitors. Syntheses, and structure-activity studies on GABA analogues containing diarybutenyl and diarylmethoxy-alkyl N-substituents
38. Synthesis and biochemical studies of spirocyclic amino acids. II. Activity of 2-azaspiro[5.5]undecane-7-carboxylates as GABA-uptake inhibitors
39. Synthesis of 4,4-bis(2-methylphenyl)-3-butenyl (and butyl) analogs of 4-phenyl-1,4- and 6-phenyl-1,6-dihydropyridine-3-carboxylic acids and their evaluation as neuronal GABA-uptake inhibitors
40. On the bioactive conformation of the GABA uptake inhibitor SK&F 89976-A
41. GABA receptors and GABAergic synapses as targets for drug development
42. The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of R-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate
43. A review of the preclinical pharmacology of tiagabine: A potent and selective anticonvulsant GABA uptake inhibitor
44. Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus
45. Update on the mechanism of action of antiepileptic drugs
46. Tiagabine pharmacology in profile
47. Pharmacokinetics of tiagabine, a γ-aminobutyric acid-uptake inhibitor, in healthy subjects after single and multiple doses
48. Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents
49. Antihistamine substances. Tricyclic analogues of N-(4,4-diphenyl-3-butene-1-yl)nipecotic acid and some related compounds
50. Effects of tricyclic and tetracyclic antidepressants on the three subtypes of GABA transporter
51. Preparation of unsaturated heterocyclic compounds. II. Synthesis of guvacine
52. Anticonvulsants. 1. Dibenzo[a,d]-1,4-cycloheptadiene-5-carboxamide and related compounds
53. Synthetic oxytocics. I. 3-(piperidyl-(N)-methyl)indoles and related compounds
54. Absolute configuration and optical purity of 3-substituted piperidines
55. An improved synthesis and resolution of potentially neuroleptic rigid spiro amines
56. Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds
57. Reactions of condensed N-heteroaromatic molecules. II. Electrophilic substitution of N-acetyl-carbazole, N-acetyl-10,11-dihydrodibenz-[b,f]azepine and derivatives
58. Synthesis of dibenzo [b,f]cycloprop[d]azepine derivatives. II. Introduction of a cyclopropane ring by the dichloromethylene transfer reaction
59. The protection of hydroxyl groups
60. Chemistry of 1,1-dioxothiopyrans. 2. Synthesis, structure, and properties of 4-diazo-2,6-diphenyl-4H-thiopyra-4,1,1-dioxide
61. 5-1-azabicyclo[4.3.0]nonane
62. Synthesis of a cyclopropyl carbinol in the amitriptyline series
63. Fulvenes and thermochromic ethylenes. Part LX. The conformation of 5H-dibenzo[a,d]cyclohepten-5-one and 10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5-one
64. Novel analogues of tricyclic psychopharmacological agents
65. New psychotropic agents. Derivatives of dibenzo-[a,d]-1,4-cycloheptadiene
66. Comparison of the reactions of grignard reagents and dialkylmagnesium compounds in addition, reduction, and enolization reactions
67. 3H]-GABA into rat brain synaptosomes
68. Cloning of the human brain GABA transporter
69. Cloning and expression of a rat brain GABA transporter
70. GABA transporter protein cloned from rat brain
71. A GABA transporter cDNA has been cloned
72. Crystal and molecular structures of tricyclic neuroleptics
73. Conformationally restricted tricyclic antidepressants. 1. Octahydrobenzazepinonnaphthyridines as rigid imipramine analogues
74. Rapid chromatographic technique for preparative separations with moderate resolution