78755-80-3Relevant articles and documents
Preparation method of flumazenil
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Paragraph 0176; 0181-0184, (2021/06/22)
The invention discloses a preparation method of flumazenil, and belongs to the field of medicine synthesis. The method comprises the following steps: by taking 5-fluoro-2-nitrobenzoic acid as a raw material, carrying out condensation on 5-fluoro-2-nitrobenzoic acid and sarcosine ester, and then carrying out ring closing while reducing, so as to obtain 7-fluoro-3, 4-dihydro-4-methyl-1H-[1, 4] benzodiazepine-2, 5-diketone; and finally, carrying out halogenation and cycloaddition reaction to obtain flumazenil. According to the novel synthesis method of the flumazenil key intermediate 7-fluoro-3, 4-dihydro-4-methyl-1H-[1, 4] benzodiazepine-2, 5-diketone, provided by the invention, a green synthesis process is adopted, an intramolecular cyclization reaction is performed while a nitro group is reduced, and compared with a known flumazenil synthesis method, a strong oxidant, a highly toxic reagent (such as ethyl chloroformate) and the like are not needed, and the yield is higher.
Benzodiazepine derivative and preparation method and application thereof
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, (2021/07/10)
The invention discloses a benzodiazepine derivative as shown in a formula (I), enantiomers, diastereoisomers, racemes and mixtures thereof, pharmaceutically acceptable salts, crystalline hydrates and solvates thereof, a preparation method thereof, and application of the derivative in the preparation of antidotes of GABAA receptor agonists, post-anesthesia awakening agents, anti-epileptic drugs, anti-senile dementia drugs, ethanol poisoning antidotes and awakening agents for treating consciousness loss caused by unknown reasons.
Preparation and application method of stable isotope substituted flumazenil compound
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Paragraph 0045; 0049, (2021/09/04)
The invention provides a preparation method and an application method of a stable isotope substituted flumazenil compound. The chemical structural general formula of the flumazenil compound is shown in the specification, wherein R1, R2, R3, R5, R6 and/or R7 are hydrogen or deuterium independently; R4 and/or R8 represent branched or linear C1-C4 alkyl, no or one or more hydrogen atoms are substituted by deuterium; at least one hydrogen atom in R1 and R8 is substituted by deuterium. Beneficial effects are that the deuterated flumazenil compound can stably exist in a human body as a contrast agent, the human body cannot be hurt by multiple times of detection, the conversion of deuterium labeling can be directly monitored by using standard magnetic resonance spectrum acquisition hardware and signal processing, the method is simple and practical, the precision is high, the result is reliable, and the metabolic condition can be quantitatively and specifically analyzed.
PENTACYCLIC COMPOUND
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Paragraph 0088-0091, (2019/03/14)
The present invention provides compounds represented by formulas (I) to (VI) or pharmaceutically acceptable salts thereof.
The development of potential new fluorine-18 labelled radiotracers for imaging the GABAA receptor
Jackson, Alexander,Guilbert, Benedicte B.,Plant, Stuart D.,Goggi, Julian,Battle, Mark R.,Woodcraft, John L.,Gaeta, Alessandra,Jones, Clare L.,Bouvet, Denis R.,Jones, Paul A.,O'Shea, Dennis M.,Zheng, Penny Hao,Brown, Samantha L.,Ewan, Amanda L.,Trigg, William
, p. 821 - 826 (2013/03/13)
Positron emission tomography (PET) using the tracer [11C] Flumazenil has shown changes in the distribution and expression of the GABA A receptor in a range of neurological conditions and injury states. We aim to develop a fluorine-18 labelled PET agent with comparable properties to [11C]Flumazenil. In this study we make a direct comparison between the currently known fluorine-18 labelled GABAA radiotracers and novel imidazobenzodiazepine ligands. A focussed library of novel compound was designed and synthesised where the fluorine containing moiety and the position of attachment is varied. The in vitro affinity of twenty-two compounds for the GABAA receptor was measured. Compounds containing a fluoroalkyl amide or a longer chain ester group were eliminated due to low potency. The fluorine-18 radiochemistry of one compound from each structural type was assessed to confirm that an automated radiosynthesis in good yield was feasible. Eleven of the novel compounds assessed appeared suitable for in vivo assessment as PET tracers.
On the reaction of fused benzodiazepines with alkynes containing electron-withdrawing groups
Voskressensky,Borisova,Babakhanova,Akbulatov,Tsar'Kova,Titov,Khrustalev,Varlamov
, p. 1220 - 1230 (2013/07/26)
Fused benzodiazepines were found to react with activated alkynes to effect either vinylation of unsubstituted nitrogen atom or dealkylation of nitrogen and its further vinylation. For benzodiazepinones bearing lactam fragment, the reactions with alkynes proceed by several pathways: formation of vinyl-substituted benzodiazepines, the Stevens rearangement products, and expansion of the diazepine ring: benzodiazonine and diazecine.
Method of making diazepine derivatives
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, (2008/06/13)
The present invention relates to a process for manufacturing diazepine derivatives of the general formula I wherein R1is lower alkyl and R2is hydrogen, or R1and R2are together —(CH2)n— and n is 2 or 3; R3is halogen, lower alkyl, lower alkoxy and m is 0, 1 or 2; R4is hydrogen or lower alkyl. The compounds of general formula I are valuable intermediate products for the manufacture of imidazo [1,5-a][1,4]diazepine derivatives, like for instance 7-chloro-3-(5-dimethylaminomethyl-[1,2,4]oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo[1,5-a][1,4]benzodiazepin-6-one, which diazepine derivatives show excellent psychopharmacological properties as agonists of the central benzodiazepine receptors.
Imidazo-diazepines and their use
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, (2008/06/13)
There is provided imidazodiazepines of the formula STR1 wherein A together with the two carbon atoms denoted as α and β is the group STR2 X is an oxygen or sulphur atom and R 1 is hydrogen or lower alkyl, and either R 2 is hydrogen, trifluoromethyl, halogen, cyano or nitro and R 3 is hydrogen or R 2 is hydrogen and R 3 is trifluoromethyl, halogen, cyano, nitro or lower alkyl,and their pharmaceutically acceptable acid addition salts. The compounds are useful in the antagonization of the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity, for example as antidotes in the case of intoxications with 1,4-benzodiazepines which have tranquillizing activity.Also presented are methods to produce the above imidazodiazepines.
Imidazodiazepine derivatives
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, (2008/06/13)
Imidazodiazepine derivatives of the formula STR1 wherein A together with the two carbon atoms denoted as α and β is selected from the group consisting of STR2 the dotted line represents the double bond present in groups (a) and (b), D is >C O or >C S, R 1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR 4, R 4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R 5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R 6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R 2 is hydrogen and R 3 is hydrogen or lower alkyl or R 2 and R 3 together are trimethylene or propenylene and the carbon atom denoted as γ has the S- or R,S-configuration, and pharmaceutically acceptable salts thereof are presented and have utility for antagonizing the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can be used, for example, as antidotes in the case of intoxications in which excessive intake of 1,4-benzodiazepines which have tranquillizing participates, or for shortening an anaesthesia induced by such 1,4-benzodiazepines. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines such as (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one.Also presented are processes to produce the imidazodiazepine derivatives and intermediates therefor.
