9-Carboxymethyl-5 H ,10 H -imidazo[1,2- a ]indeno[1,2- e ]pyrazin-4-one-2-carbocylic Acid (RPR117824): Selective Anticonvulsive and Neuroprotective AMPA Antagonist

Mignani, Serge; Böhme, Georg Andrees; Birraux, Guillaume; Boireau, A.; Jimonet, Patrick; Damour, D.; Genevois-Borella, Arielle; Debono, Marc; Pratt, Jeremy; Vuilhorgne, Marc; Wahl, Florence; Stutzmann, Jean‐Marie

doi:10.1016/s0968-0896(01)00431-x

Cited by 36 publications

(15 citation statements)

References 24 publications

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“…15) were two of the most interesting compounds of this series showing high affinity and selectivity for the AMPA receptors. 334,335 Further studies demonstrated that RPR117824 was one of the most potent anticonvulsant agent in the MES test described so far. It showed to be active also in both the PTZ-induced convulsions and in the DBA/2 mice tests.…”

Section: F Imidazoindenopyrazinesmentioning

confidence: 94%

“…10) was reported. Compounds of these series were generally nonselective AMPA versus Gly/NMDA receptor antagonists, but were demonstrated to have anti-ischaemic and neuroprotective properties, [319][320][321][322][323][324][325][326][327][328][329][330][331][332][333][334] and, most importantly, low toxicity. Optimization of both the 10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one 328,335 (54, Fig.…”

Section: F Imidazoindenopyrazinesmentioning

confidence: 99%

“…Most of the disclosed derivatives showed to be potent AMPA receptor antagonists capable of penetrating the blood-brain barrier. [328][329][330][331][332][333][334] SAR studies indicated that both the position and the nature of the substituent on the tetracyclic ring system are crucial for the AMPA receptor-ligand interaction.…”

Section: F Imidazoindenopyrazinesmentioning

confidence: 99%

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Competitive AMPA receptor antagonists

Catarzi

Colotta

Varano

2006

Medicinal Research Reviews

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Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) where it is involved in the physiological regulation of different processes. It has been well established that excessive endogenous Glu is associated with many acute and chronic neurodegenerative disorders such as cerebral ischaemia, epilepsy, amiotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease. These data have consequently added great impetus to the research in this field. In fact, many Glu receptor antagonists acting at the N-methyl-D-aspartic acid (NMDA), 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), and/or kainic acid (KA) receptors have been developed as research tools and potential therapeutic agents. Ligands showing competitive antagonistic action at the AMPA type of Glu receptors were first reported in 1988, and the systemically active 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline (NBQX) was first shown to have useful therapeutic effects in animal models of neurological disease in 1990. Since then, the quinoxaline template has represented the backbone of various competitive AMPA receptor antagonists belonging to different classes which had been developed in order to increase potency, selectivity and water solubility, but also to prolong the "in vivo" action. Compounds that present better pharmacokinetic properties and less serious adverse effects with respect to the others previously developed are undergoing clinical evaluation. In the near future, the most important clinical application for the AMPA receptor antagonists will probably be as neuroprotectant in neurodegenerative diseases, such as epilepsy, for the treatment of patients not responding to current therapies. The present review reports the history of competitive AMPA receptor antagonists from 1988 up to today, providing a systematic coverage of both the open and patent literature.

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Section: F Imidazoindenopyrazinesmentioning

confidence: 94%

Section: F Imidazoindenopyrazinesmentioning

confidence: 99%

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Competitive AMPA receptor antagonists

Catarzi

Colotta

Varano

2006

Medicinal Research Reviews

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“…However, poor pharmacokinetic characteristics and potential nephrotoxicity prevented many of these compounds from being used in medicine [27,61,62,71]. Furthermore, all such compounds have some degree of affinity for Glu N receptors.…”

Section: Quinoline Quinoxaline Isatinoxime Decahydroisoquinoline mentioning

confidence: 99%

Antagonists of AMPA/KA and NMDA (glycine site) glutamate receptors

2008

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“…2 To date, only few indane-fused heterocycles have been prepared. [3][4][5][6][7][8][9][10] Because of their therapeutic interest, the syntheses of cycloalkane-fused pyrimidinones have been studied, 2 but syntheses of their indane-condensed derivatives have not yet been reported.…”

Section: Introductionmentioning

confidence: 99%