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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2001-2-5
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pubmed:abstractText |
A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticonvulsants,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazinamide,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Amino-3-hydroxy-5-methyl-4-iso...,
http://linkedlifedata.com/resource/pubmed/chemical/pyrazinoic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:BohmeG AGA,
pubmed-author:BoireauAA,
pubmed-author:BouquerelJJ,
pubmed-author:DamourDD,
pubmed-author:DebonoM WMW,
pubmed-author:Genevois-BorellaAA,
pubmed-author:HardyJ CJC,
pubmed-author:HubertPP,
pubmed-author:JimonetPP,
pubmed-author:ManfréFF,
pubmed-author:MignaniSS,
pubmed-author:NemecekPP,
pubmed-author:PrattJJ,
pubmed-author:RandleJ CJC,
pubmed-author:RibeillYY,
pubmed-author:StutzmannJ MJM,
pubmed-author:VuilhorgneMM
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
127-32
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:11206442-Animals,
pubmed-meshheading:11206442-Anticonvulsants,
pubmed-meshheading:11206442-Combinatorial Chemistry Techniques,
pubmed-meshheading:11206442-Disease Models, Animal,
pubmed-meshheading:11206442-Excitatory Amino Acid Antagonists,
pubmed-meshheading:11206442-Imidazoles,
pubmed-meshheading:11206442-Inhibitory Concentration 50,
pubmed-meshheading:11206442-Male,
pubmed-meshheading:11206442-Mice,
pubmed-meshheading:11206442-Oocytes,
pubmed-meshheading:11206442-Pyrazinamide,
pubmed-meshheading:11206442-Pyrazines,
pubmed-meshheading:11206442-Receptors, AMPA,
pubmed-meshheading:11206442-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:11206442-Seizures,
pubmed-meshheading:11206442-Structure-Activity Relationship,
pubmed-meshheading:11206442-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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pubmed:year |
2001
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pubmed:articleTitle |
Bioisosteres of 9-carboxymethyl-4-oxo-imidazo[1,2-a]indeno-[1,2-e]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent in vivo AMPA antagonists with longer durations of action.
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pubmed:affiliation |
Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
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pubmed:publicationType |
Journal Article
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