22345-47-7Relevant articles and documents
Synthesis of Tofisopam by Way of Photoinduced CO2 Fixation
Masuda, Yusuke,Makita, Katsuhiko,Ishida, Naoki,Murakami, Masahiro
, p. 4189 - 4192 (2019/11/26)
Herein reported is a unique synthetic route of Tofisopam, an anxiolytic drug containing a 2,3-benzodiazepine core structure. 3,4-Dimethoxypropylbenzene and 3,4-dimethoxybenzoic acid, which are both of plant origin, and CO2 constitute its carbon skeleton. These three renewable substances are united by two C?C bond forming reactions, i.e., a Friedel–Crafts acylation reaction and a photoinduced carboxylation reaction to construct the major carbon framework. Finally, a methyl group is introduced by a Kumada-type cross-coupling reaction to furnish Tofisopam. Various analogs of Tofisopam are readily synthesized by introducing other substituents than a methyl group at the last C?C bond forming step.
Method of lowering serum uric acid levels with (S)-tofisopam
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Page/Page column 13, (2016/09/12)
Enantiomerically-pure (S)-tofisopam is administered to lower serum uric acid levels in a mammal.
Synthesis of 2,3-benzodiazepines and 2,3-benzodiazepin-4-ones from arynes and β-diketones
Okuma, Kentaro,Tanabe, Yukiko,Nagahora, Noriyoshi,Shioji, Kosei
, p. 1064 - 1073 (2015/09/01)
2,3-Benzodiazepines were synthesized by two-step or one-pot reactions from aryne precursors. Reaction of 2- (trimethylsilyl)aryl triflates with β-diketones in the presence of CsF gave ortho-substituted benzophenones. Treatment of benzophenones with hydrazine hydrate resulted in the formation of 2,3-benzodiazepines in moderate yields. Tofisopam, a well known anxiolytic, could be synthesized via C-C bond insertion of 3,4-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in one-pot operation. 2,3-Benzodiazepin-4-ones were also synthesized by the reaction of β-keto esters with triflates in the presence of CsF, followed by the addition of hydrazine hydrate. Substituted isoquinolines were synthesized by the reaction of ortho-substituted benzophenones with ammonium hydroxide.
New, lithiation-based synthesis of tofisopam, A 2,3-benzodiazepine type anxiolytic drug
Samu, Erika Molnarne,Lukacs, Gyula,Volk, Balazs,Simig, Gyula
, p. 287 - 295 (2014/01/17)
The classical, widely-used synthesis of the anxiolytic drug tofisopam applies chromium(VI) oxide reagent for the synthesis of the diketone key intermediate. The chromium salts formed in the course of the reaction are strongly toxic compounds. In order to reduce the reagents contributing to the pollution of the environment, an alternative manufacturing process has been elaborated at our laboratory. Starting compound (3,4-dimethoxyphenyl)acetone was transformed to the ethylene ketal of (2-bromo-4,5-dimethoxyphenyl)acetone. Bromine-lithium exchange and introduction of a 3,4-dimethoxybenzoyl moiety resulted in the new key intermediate. Removal of the ketal protecting group and ring closure with hydrazine was carried out in one pot affording drug substance tofisopam.
One-pot synthesis of 2,3-benzodiazepines from arynes and β-diketones
Okuma, Kentaro,Tanabe, Yukiko,Itoyama, Ryoichi,Nagahora, Noriyoshi,Shioji, Kosei
supporting information, p. 1260 - 1262 (2013/10/22)
Novel one-pot synthesis of 2,3-benzodiazepines from aryne precursors was accomplished. Tofisopam, well-known anxiolytics, could be synthesized via C-C bond insertion of 4,5-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)- butane-1,3-dione, followed by the reaction with hydrazine hydrate in a one-pot operation. This protocol is applicable to the synthesis of other biologically active 2,3-benzodiazepines, such as Girisopam and Nerisopam.
PROCESS FOR THE PREPARATION OF HIGH PURITY 1-(3,4-DIMETHOXY-PHENYL)-5-ETHYL-7,8-DIMETHOXY-4-METHYL-5H-2,3-BENZODIAZEPINE
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Page/Page column 9, (2010/01/30)
The present invention relates to the process for the preparation of 1-(3,4-dimethoxy-phenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine of the Formula (I) by reacting 3,4,3',4'-tetramethoxy-6-(α-aceto-propyl)-benzofenon of the general Formula (II) with hydrazine or hydrazine-hydrate in alcoholic medium, and isolating and purifying the reaction product with a clarifier, which comprises using during the clarifying step a recrystallization solution having an iron content lower than 7 ppm.
Phosphodiesterase inhibitors
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Page/Page column 10-11, (2008/06/13)
The invention relates especially to novel stereospecific derivatives of 2,3-benzodiazepine type as inhibitors of phosphodiesterases, especially 2 and 4, and uses thereof in the therapeutic field, most particularly for preventing and treating pathologies involving a central and/or peripheral disorder. The compounds of the invention more particularly correspond to the general formulae (I) and (II):
Conversion process for 2,3-benzodiazepine enantiomers
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Page/Page column 2, (2008/06/13)
Methods for the racemization of an enantiomer of a 2,3-benzodiazepine molecule into the corresponding racemic mixture under either basic or acidic conditions are described. Furthermore, the invention relates to the conversion of an enantiomer of tofisopam or its metabolites to the corresponding opposite enantiomer.
Treatment of inflammatory disorders with 2,3- benzodiazepines
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, (2008/06/13)
Compounds according to formula I: 1 wherein R1, R2, R3, R4, R5 and n are as defined herein, are administered for the treatment of inflammatory disorders, particularly inflammatory disorders mediated by LTB4,
Method of increasing neutrophil production using 2,3-benzodiazepines
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, (2008/06/13)
Compounds according to formula I: wherein R1, R2, R3, R4, R5 and n are as defined herein, are administered to increase neutrophil levels in mammals.
