【药物名称】RPR-119990
化学结构式(Chemical Structure):
参考文献No.52054
标题:5H-10H-Imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one derivs., preparation thereof, and drugs containing said derivs.
作者:Aloup, J.-C.; Hardy, J.-C.; Mignani, S.; Jimonet, P.; Audiau, F.; Barreau, M.; Manfre, F.; Damour, D.; Ribeill, Y.; Genevois-Borella, A.; Nemecek, P. (Aventis Pharma SA)
来源:WO 9631511
合成路线图解说明:

The cyclization of 3-[2-(carboxymethyl)phenyl]propionic acid (I) in the presence of conc. H2SO4 at 100 C gives 2-(1-oxoindan-4-yl)acetic acid (II), which is esterified with (COCl)2 and EtOH to yield the ethyl ester (III). The bromination of (III) with Br2 in HOAc affords 2-(2-bromo-1-oxoindan-4-yl)acetic acid ethyl ester (IV). The condensation of (IV) with 4-(diethoxyphosphoryl)-1H-imidazole-2-carboxylic acid ethyl ester (V) (obtained by cyclization of hydroxyamidinocarboxylic acid ethyl ester (VI) with ethynylphosphonic acid diethyl ester (VII) in the presence of TEA) provides the adduct (VIII). The cyclization of (VIII) with ammonium acetate in refluxing acetic acid gives the tetracyclic phosphonate (IX), which is finally hydrolyzed with refluxing aqueous HCl to yield the target phosphonic acid.

参考文献No.606964
标题: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 wit longer durations of action
作者:Jimonet, P.; Bohme, G.A.; Bouquerel, J.; Boireau, A.; Damour, D.; Debono, M.W.; Genevois-Borella, A.; Hardy, J.C.; Hubert, P.; Manfre, F.; Nemecek, P.; Pratt, J.; Randle, J.C.; Ribeill, Y.; Stutzmann, J.M.; Vuilhorgne, M.; Mignani, S.
来源:Bioorg Med Chem Lett 2001,11(2),127
合成路线图解说明:

The cyclization of 3-[2-(carboxymethyl)phenyl]propionic acid (I) in the presence of conc. H2SO4 at 100 C gives 2-(1-oxoindan-4-yl)acetic acid (II), which is esterified with (COCl)2 and EtOH to yield the ethyl ester (III). The bromination of (III) with Br2 in HOAc affords 2-(2-bromo-1-oxoindan-4-yl)acetic acid ethyl ester (IV). The condensation of (IV) with 4-(diethoxyphosphoryl)-1H-imidazole-2-carboxylic acid ethyl ester (V) (obtained by cyclization of hydroxyamidinocarboxylic acid ethyl ester (VI) with ethynylphosphonic acid diethyl ester (VII) in the presence of TEA) provides the adduct (VIII). The cyclization of (VIII) with ammonium acetate in refluxing acetic acid gives the tetracyclic phosphonate (IX), which is finally hydrolyzed with refluxing aqueous HCl to yield the target phosphonic acid.

参考文献No.640758
标题:RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: Synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis
作者:Canton, T.; B鰄me, G.A.; Boireau, A.; Bordier, F.; Mignani, S.; Jimonet, P.; Jahn, G.; Alavijeh, M.; Stygall, J.; Roberts, S.M.; Brealey, C.; Vuilhorgne, M.; Debono, M.W.; Le Guern, S.; Laville, M.; Briet, D.; Roux, M.; Stutzmann, J.M.; Pratt, J.
来源:J Pharmacol Exp Ther 2001,299(1),314
合成路线图解说明:

The cyclization of 3-[2-(carboxymethyl)phenyl]propionic acid (I) in the presence of conc. H2SO4 at 100 C gives 2-(1-oxoindan-4-yl)acetic acid (II), which is esterified with (COCl)2 and EtOH to yield the ethyl ester (III). The bromination of (III) with Br2 in HOAc affords 2-(2-bromo-1-oxoindan-4-yl)acetic acid ethyl ester (IV). The condensation of (IV) with 4-(diethoxyphosphoryl)-1H-imidazole-2-carboxylic acid ethyl ester (V) (obtained by cyclization of hydroxyamidinocarboxylic acid ethyl ester (VI) with ethynylphosphonic acid diethyl ester (VII) in the presence of TEA) provides the adduct (VIII). The cyclization of (VIII) with ammonium acetate in refluxing acetic acid gives the tetracyclic phosphonate (IX), which is finally hydrolyzed with refluxing aqueous HCl to yield the target phosphonic acid.

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