Synthesis of anticonvulsive AMPA antagonists: 4-Oxo-10-substituted-imidazo[1,2- a]indeno[1,2- e]pyrazin-2-carboxylic acid derivatives
The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2- a]indeno[1,2...
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Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2001-05, Vol.11 (9), p.1205-1210 |
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creator | Stutzmann, Jean-Marie Bohme, Georg Andrees Boireau, Alain Damour, Dominique Debono, Marc Williams Genevois-Borella, Arielle Jimonet, Patrick Pratt, Jeremy Randle, John C.R Ribeill, Yves Vuilhorgne, Marc Mignani, Serge |
description | The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid derivatives was synthesized. The most potent derivative
6a exhibited nanomolar binding affinity (IC
50=35
nM) and antagonist activity (IC
50=6
nM) at ionotropic AMPA receptor. This compound also demonstrated potent anticonvulsant properties in MES in mice and rats with long durations of action with ED
50 values in the 1–3
mg/kg dose range following ip and iv administration.
The 4-oxo-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid
1 exhibited strong binding affinity for the AMPA receptor (IC
50=35
nM) and potent antagonist activity against electrophysiological responses (IC
50=6
nM). Compound
1 demonstrated also an anticonvulsant effect at low doses in MES test with ED
50 values between 1 and 3 mg/kg dose range following ip and iv administration (mouse) and extended long duration of action following iv administration (mouse and rats). |
doi_str_mv | 10.1016/S0960-894X(01)00180-9 |
format | Article |
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a]indeno[1,2-
e]pyrazin-2-carboxylic acid derivatives was synthesized. The most potent derivative
6a exhibited nanomolar binding affinity (IC
50=35
nM) and antagonist activity (IC
50=6
nM) at ionotropic AMPA receptor. This compound also demonstrated potent anticonvulsant properties in MES in mice and rats with long durations of action with ED
50 values in the 1–3
mg/kg dose range following ip and iv administration.
The 4-oxo-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid
1 exhibited strong binding affinity for the AMPA receptor (IC
50=35
nM) and potent antagonist activity against electrophysiological responses (IC
50=6
nM). Compound
1 demonstrated also an anticonvulsant effect at low doses in MES test with ED
50 values between 1 and 3 mg/kg dose range following ip and iv administration (mouse) and extended long duration of action following iv administration (mouse and rats).</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(01)00180-9</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Medical sciences ; Neuropharmacology ; Pharmacology. Drug treatments</subject><ispartof>Bioorganic & medicinal chemistry letters, 2001-05, Vol.11 (9), p.1205-1210</ispartof><rights>2001 Elsevier Science Ltd</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0960-894X(01)00180-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=971809$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Stutzmann, Jean-Marie</creatorcontrib><creatorcontrib>Bohme, Georg Andrees</creatorcontrib><creatorcontrib>Boireau, Alain</creatorcontrib><creatorcontrib>Damour, Dominique</creatorcontrib><creatorcontrib>Debono, Marc Williams</creatorcontrib><creatorcontrib>Genevois-Borella, Arielle</creatorcontrib><creatorcontrib>Jimonet, Patrick</creatorcontrib><creatorcontrib>Pratt, Jeremy</creatorcontrib><creatorcontrib>Randle, John C.R</creatorcontrib><creatorcontrib>Ribeill, Yves</creatorcontrib><creatorcontrib>Vuilhorgne, Marc</creatorcontrib><creatorcontrib>Mignani, Serge</creatorcontrib><title>Synthesis of anticonvulsive AMPA antagonists: 4-Oxo-10-substituted-imidazo[1,2- a]indeno[1,2- e]pyrazin-2-carboxylic acid derivatives</title><title>Bioorganic & medicinal chemistry letters</title><description>The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid derivatives was synthesized. The most potent derivative
6a exhibited nanomolar binding affinity (IC
50=35
nM) and antagonist activity (IC
50=6
nM) at ionotropic AMPA receptor. This compound also demonstrated potent anticonvulsant properties in MES in mice and rats with long durations of action with ED
50 values in the 1–3
mg/kg dose range following ip and iv administration.
The 4-oxo-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid
1 exhibited strong binding affinity for the AMPA receptor (IC
50=35
nM) and potent antagonist activity against electrophysiological responses (IC
50=6
nM). Compound
1 demonstrated also an anticonvulsant effect at low doses in MES test with ED
50 values between 1 and 3 mg/kg dose range following ip and iv administration (mouse) and extended long duration of action following iv administration (mouse and rats).</description><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNo9kNtKAzEQhoMoWA-PICx4o2B0kk2bxhspxRMoCioIImE2yepIzZZNWqz3vrdbFa-Gmf9jZvgY2xFwKEAMju7ADIAPjXrcA7EPIIbAzQrrCTVQvFTQX2W9f2SdbaT01kEKlOqxr7tFzK8hUSqausCYyTVxPpskmodidH07Ws7wpYmUcjouFL_5aLgAnmZVypRnOXhO7-Txs3kSB5IX-EzRh_jXhefposVPilxyh23VfCwm5Ap05AsfWppj7g6lLbZW4ySF7b-6yR7OTu_HF_zq5vxyPLriQZY6c1_JEo33JtR9jd6JUg1ljVJrQKMxOOV11WUlDIz2_dJIPYRKCumcgAB1ucl2f_dOMTmc1C1GR8lOW3rHdmGN7tSZjjr5pUL3ypxCa5OjEF3w1AaXrW_ICrBL9_bHvV2KtSDsj3trym8ADnnV</recordid><startdate>20010507</startdate><enddate>20010507</enddate><creator>Stutzmann, Jean-Marie</creator><creator>Bohme, Georg Andrees</creator><creator>Boireau, Alain</creator><creator>Damour, Dominique</creator><creator>Debono, Marc Williams</creator><creator>Genevois-Borella, Arielle</creator><creator>Jimonet, Patrick</creator><creator>Pratt, Jeremy</creator><creator>Randle, John C.R</creator><creator>Ribeill, Yves</creator><creator>Vuilhorgne, Marc</creator><creator>Mignani, Serge</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope></search><sort><creationdate>20010507</creationdate><title>Synthesis of anticonvulsive AMPA antagonists: 4-Oxo-10-substituted-imidazo[1,2- a]indeno[1,2- e]pyrazin-2-carboxylic acid derivatives</title><author>Stutzmann, Jean-Marie ; Bohme, Georg Andrees ; Boireau, Alain ; Damour, Dominique ; Debono, Marc Williams ; Genevois-Borella, Arielle ; Jimonet, Patrick ; Pratt, Jeremy ; Randle, John C.R ; Ribeill, Yves ; Vuilhorgne, Marc ; Mignani, Serge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e237t-db23a9dd9ef57adc13482fa2770a97aec4d7bef530697d5392780b212cc10e0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stutzmann, Jean-Marie</creatorcontrib><creatorcontrib>Bohme, Georg Andrees</creatorcontrib><creatorcontrib>Boireau, Alain</creatorcontrib><creatorcontrib>Damour, Dominique</creatorcontrib><creatorcontrib>Debono, Marc Williams</creatorcontrib><creatorcontrib>Genevois-Borella, Arielle</creatorcontrib><creatorcontrib>Jimonet, Patrick</creatorcontrib><creatorcontrib>Pratt, Jeremy</creatorcontrib><creatorcontrib>Randle, John C.R</creatorcontrib><creatorcontrib>Ribeill, Yves</creatorcontrib><creatorcontrib>Vuilhorgne, Marc</creatorcontrib><creatorcontrib>Mignani, Serge</creatorcontrib><collection>Pascal-Francis</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stutzmann, Jean-Marie</au><au>Bohme, Georg Andrees</au><au>Boireau, Alain</au><au>Damour, Dominique</au><au>Debono, Marc Williams</au><au>Genevois-Borella, Arielle</au><au>Jimonet, Patrick</au><au>Pratt, Jeremy</au><au>Randle, John C.R</au><au>Ribeill, Yves</au><au>Vuilhorgne, Marc</au><au>Mignani, Serge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of anticonvulsive AMPA antagonists: 4-Oxo-10-substituted-imidazo[1,2- a]indeno[1,2- e]pyrazin-2-carboxylic acid derivatives</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><date>2001-05-07</date><risdate>2001</risdate><volume>11</volume><issue>9</issue><spage>1205</spage><epage>1210</epage><pages>1205-1210</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid derivatives was synthesized. The most potent derivative
6a exhibited nanomolar binding affinity (IC
50=35
nM) and antagonist activity (IC
50=6
nM) at ionotropic AMPA receptor. This compound also demonstrated potent anticonvulsant properties in MES in mice and rats with long durations of action with ED
50 values in the 1–3
mg/kg dose range following ip and iv administration.
The 4-oxo-imidazo[1,2-
a]indeno[1,2-
e]pyrazin-2-carboxylic acid
1 exhibited strong binding affinity for the AMPA receptor (IC
50=35
nM) and potent antagonist activity against electrophysiological responses (IC
50=6
nM). Compound
1 demonstrated also an anticonvulsant effect at low doses in MES test with ED
50 values between 1 and 3 mg/kg dose range following ip and iv administration (mouse) and extended long duration of action following iv administration (mouse and rats).</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><doi>10.1016/S0960-894X(01)00180-9</doi><tpages>6</tpages></addata></record> |
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source | Elsevier ScienceDirect Journals Complete |
subjects | Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Medical sciences Neuropharmacology Pharmacology. Drug treatments |
title | Synthesis of anticonvulsive AMPA antagonists: 4-Oxo-10-substituted-imidazo[1,2- a]indeno[1,2- e]pyrazin-2-carboxylic acid derivatives |
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