- A flupirtin derivative and its inorganic acid salt preparation method (by machine translation)
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The invention relates to a kind of flupirtine derivative and its inorganic acid salt of the preparation method, the [...] derivatives by the following chemical formula 1 that: The [...] derivative is maleic acid flupirtin synthesis process and/or storage of produced in the process of an important impurity. The preparation method according to this application, and may be the above-mentioned yield of flupirtine derivative and its inorganic acid salt, each step of the reaction yield can be up to 55% or more. (by machine translation)
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Paragraph 0052-0054; 0057-0058; 0065; 0068-0069; 0076
(2019/10/22)
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- Method for preparing flupirtine hydrochloride
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The invention discloses a method for preparing flupirtine hydrochloride. The method comprises the following steps: adopting 2,6-dichloro-3-nitropyridine as an initial material, performing ammonolysis,substituting fluorobenzylamine, purifying, hydrogenating, performing acylation reaction, filtering, precipitating crystals and decompression drying to obtain the flupirtine hydrochloride. The methodis simple in operation, capable of simultaneously performing the hydrogenation and acylation reaction, capable of avoiding the deterioration of polyamino pyridine derivatives as far as possible, capable of titrating ethyl chloroformate without opening a kettle cover, and capable of reducing the harm on the human body.
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Paragraph 0015
(2019/01/14)
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- Discovery of Aromatic Carbamates that Confer Neuroprotective Activity by Enhancing Autophagy and Inducing the Anti-Apoptotic Protein B-Cell Lymphoma 2 (Bcl-2)
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Neurodegenerative diseases share certain pathophysiological hallmarks that represent common targets for drug discovery. In particular, dysfunction of proteostasis and the resultant apoptotic death of neurons represent common pathways for pharmacological intervention. A library of aromatic carbamate derivatives based on the clinically available drug flupirtine was synthesized to determine a structure-activity relationship for neuroprotective activity. Several derivatives were identified that possess greater protective effect in human induced pluripotent stem cell-derived neurons, protecting up to 80% of neurons against etoposide-induced apoptosis at concentrations as low as 100 nM. The developed aromatic carbamates possess physicochemical properties desirable for CNS therapeutics. The primary known mechanisms of action of the parent scaffold are not responsible for the observed neuroprotective activity. Herein, we demonstrate that neuroprotective aromatic carbamates function to increase the Bcl-2/Bax ratio to an antiapoptotic state and activate autophagy through induction of beclin 1.
- Kinarivala, Nihar,Patel, Ronak,Boustany, Rose-Mary,Al-Ahmad, Abraham,Trippier, Paul C.
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p. 9739 - 9756
(2017/12/26)
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- QUINOLIUM CONJUGATES OF CYCLOSPORIN
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The present invention relates to conjugates of cyclosporin with quinolium mitochondrial targeting groups, and their therapeutic uses.
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Page/Page column 27; 28
(2016/03/18)
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- A method for synthesis of flupirtine maleate
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The invention provides a synthesis method of flupirtine maleate. Recrystallization by use of methanol is carried out in the refining step of the crude product of the flupirtine maleate so that the product is white in appearance and high in purity, and the crystal form of the product is pure A crystal and same as the crystal form of the commercial products. The optimal reaction solvent, reaction time and reaction temperature are explored and found out by use of a simplified process flow, and a method for preparing the flupirtine maleate in the pure A crystal form, which is high in yield, low in cost and simple to operate, uses easily available raw materials and is applicable to the industrial production is found.
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Paragraph 0119; 0121
(2016/10/09)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGIC DISEASES
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The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of neurologic diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, migraine, neuropathic pain, post herpetic neuralgia, pain, Creutzfeld-Jakob disease, Alzheimer's disease, multiple sclerosis, Batten disease, multiple sclerosis, Parkinson's disease (PD), restless legs syndrome (RLS), cluster headache, depression, fibromyalgia, sexual dysfunction, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, autism, bipolar disorder and anxiety disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder, schizophrenia, neuropathic pain, seizures, bipolar disorder and mania.
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Paragraph 0111; 0116; 0117
(2015/06/10)
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- 2,3-Dihydrospiro[1H-4- and 5-azabenzimidazole-2,1'-cyclohexane] (= spiro[cyclohexane-1,2'(3'H)-1'H-imidazo[4,5-b]pyridine] and spiro[cyclohexane-1,2'(3'H)-1'H-imidazo[4,5-c]pyridine]): Reactions with nucleophiles
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The readily available title compounds 4a and 24 react with N-, O-, S-, and C-nucleophiles in presence of MnO2 to give the corresponding mono- or disubstituted 2H-azabenzimidazoles (= azaisobenzimidazoles), e.g., 11-18 and 26a-h, respectively, or 2,3-dihydro-1H-azabenzimidazoles (= dihydro-azabenzimidazoles) such as 9 and 10 and 27 and 28, respectively, by a 1,4- or 1,6-Michael addition (Schemes 2 and 4). The bromo-dihydro-1H-azabenzimidazole 4b lost the Br-atom when treated with piperidine or morpholine yielding the corresponding disubstituted 2H-azabenzimidazole 21 (Scheme 3). Reductive ring opening of the substituted spiro compounds leads to mono- and disubstituted diaminopyridines which are intermediates for fused pyridine ring systems with substituents often not available by conventional routes and of potential pharmaceutical interest (see 32-37). E.g., starting from 4a, a three-step synthesis of the analgesic flupirtine maleate (= ethyl {2-amino-6-[(4-fluorobenzyl)amino]pyridin-3-yl}carbamate maleate = Katadolon; 39) and of its non-fluorinated derivative D-7195 is described. Its analogue 40 was similarly made from the spiro compound 24.
- Schwoch,Kramer,Neidlein,Suschitzky
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p. 2175 - 2190
(2007/10/02)
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- Synthesis and quantitative structure-activity relationships of anticonvulsant 2,3,6-triaminopyridines
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The synthesis of 2,3,6-triaminopyridine derivatives, representing a unique chemical structure for anticonvulsants, is described. The synthetic program was performed (a) to identify more potent analogs, (b) to determine structural properties controlling potency as well as neurotoxicity, and (c) to reduce the requirements for animal testing. As a result, besides other structural properties, the overall molecular lipophilicity (log k', octanol- coated column) explained changes in anticonvulsant potency and neurotoxicity. Mimicking the interaction of the amphiphilic triaminopyridines with biological membranes, NMR experiments in the presence of lecithin vesicles were conducted in order to measure the phospholipid-binding parameter log Δ(1/T2). Replacement of log k' with log Δ(1/T2) in the correlation analysis afforded a more significant equation describing the anticonvulsant activity of 21 derivatives.
- Seydel,Schaper,Coats,Cordes
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p. 3016 - 3022
(2007/10/02)
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- New triaminopyridines with a central analgesic activity
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2-Amino-3-((prop-1-en-3-yl) oxycarbonylamino)-6-(4-fluorobenzyl amino)pyridine hydrochloride (D-19050) is a centrally and peripherally acting analgesic with rapid onset, long duration of action and a good therapeutic range. D-19050 can be obtained in a 5-step-synthesis starting from 2,6-dichloropyridine.
- Emig,Nickel,Weischer,Szelenyi,Engel
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p. 627 - 631
(2007/10/02)
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