- Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
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Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
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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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- Of retigabine and wherein the intermediate preparation method (by machine translation)
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The invention relates to the medicine synthesis field and in particular relates to a preparation method of retigabine and an intermediate thereof. The method specifically comprises the following steps of: (1) preparing a compound with a structure of formula (RET25) by the compound with the structure of formula (RET20) and 4-fluorobenzaldehyde under the action of p-toluene sulfonic acid; (2) preparing the compound with the structure of formula (RET30) by the compound with the structure of formula (RET25) through sodium borohydride reduction; and (3) preparing the retigabine by the compound with the structure of the formula (RET30) through raney nickel hydrogenation reduction. The total impurity content of the retigabine obtained by the preparation method disclosed by the invention is less than 0.16% in terms of area percentage unit of HPLC (High Performance Liquid Chromatography).
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- Process for the preparation of an anticonvulsant compound
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The invention provides a novel method for the preparation of intermediates useful in a process designed to obtain known 1,2,4-triaminobenzene compounds, and in particular a specific compound thereof having known anticonvulsant activity. Unlike known methods, the novel method does not require advance protection of the amino groups present on the substrate.
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- PROCESS FOR THE PREPARATION OF AN ANTICONVULSANT COMPOUND
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The invention provides a novel method for the preparation of intermediates useful in a process designed to obtain known 1,2,4-triaminobenzene compounds, and in particular a specific compound thereof having known anticonvulsant activity. Unlike known methods, the novel method does not require advance protection of the amino groups present on the substrate.
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- PROCESS FOR THE PREPARATION OF RETIGABINE OF THE FORMULA I AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The invention relates to process for the preparation of 2-amino-4-(4- fluorobenzylamino)-l-ethoxycarbonylaminobenzene generically known as Retigabine of the formula (I) and its pharmaceutically acceptable salts e.g. Formula IA, particularly to the modification over the prior art processes-I and II disclosed therein in US5384330. The modifications are depicted in the scheme I and scheme II respectively. Disclosed herein are also the novel processes for the preparation of intermediates of formulae M, N and O of the process-I and of formulae R, S, T of process-II, those are used for preparation of Retigabine of the formula I and its pharmaceutically acceptable salts thereof.
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF RETIGABINE
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A method for the preparation of retigabine starting with intermediate III is disclosed, comprising the step of protecting the secondary amine of III with a protecting group followed by N-ethoxycarbonylation of the primary amino group of the product obtained. The preparation of retigabine is completed by steps comprising removal of the protecting group and reduction of the nitro group to amino, which can be performed in any order or simultaneously. Novel intermediates usable with said method are also described.
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Page/Page column 9
(2013/08/15)
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- PROCESS FOR THE PREPARATION OF RETIGABINE
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This invention relates to a novel chemical process for the synthesis of 2-ethyoxycarbonylamino-5-(4-fluorobenzylamino)-nitrobenzene and its use in the preparation of 2-amino-4-(4-fluorobenzylamino)-1-ethoxycarbonylaminobenzene (retigabine/ezogabine) and its polymorphic forms thereof.
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- DIETHYL 4-(4-FLUOROBENZYLAMINO)-1,2-PHENYLENEDICARBAMATE, AND SALTS THEREOF
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Disclosed are diethyl 4-(4-fluorobenzylamino)-l,2-phenylenedicarbamate (IV) and salts thereof, which are useful as reference markers and reference standards for analyzing samples comprising retigabine or salts thereof. Also disclosed is a process for prep
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Page/Page column 18
(2011/02/24)
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- Methods for treating hyperactive gastric motility
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This invention provides methods and pharmaceutical compositions for treating, inhibiting or preventing hyperactive gastric motility in a mammal utilizing agonists of KCNQ potassium channels, including KCNQ2, KCNQ3, KCNQ4 and KCNQ5 potassium channels, alone or in combination. The hyperactive gastric motility may be associated with maladies including, colitis, irritable bowel syndrome and Crohn's disease. Compounds useful in these methods include the 1,2,4-triamino-benzene derivatives described in U.S. Pat. No. 5,384,330 (Dieter et al.) and the substituted 3-phenyl oxindole compounds described in U.S. Pat. No. 5,565,483 (Hewawasam et al.). Among the preferred compounds of this invention is N-[2-amino-4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester, also referred to as retigabine.
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- Methods of treating anxiety disorders
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This invention provides methods for treating, preventing or inhibiting anxiety, anxiety-related conditions and phobias in a mammal using compounds of the formula: wherein: R1 is H, alkyl, alkanoyl or the radical Ar; R2 is H or alkyl; R3 is alkoxy, NH2, alkylamino, dialkylamino, amino substituted by the radical Ar, alkyl, alkenyl, alkynyl, or the radicals Ar or ArO—; R4 is H, alkyl or the radical Ar; R5 is H or alkyl or the radical Ar; or a pharmaceutically acceptable salt or ester form thereof; Ar is an optionally substituted phenyl radical; and n is 0 or 1, or a pharmaceutically acceptable salt or ester form thereof, with the methods particularly including the use of N-[2-amino-4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester, also known as retigabine.
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- Methods for modulating bladder function
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This invention provides methods and pharmaceutical compositions for maintaining bladder control or treating urinary incontinence in a mammal utilizing agonists of KCNQ potassium channels, including KCNQ2, KCNQ3, KCNQ4 and KCNQ5 potassium channels, alone or in combination. Compounds useful in these methods include the 1,2,4-triamino-benzene derivatives described in U.S. Pat. No. 5,384,330 (Dieter et al.) and the substituted 3-phenyl oxindole compounds described in U.S. Pat. No. 5,565,483 (Hewawasam et al.). Among the preferred compounds of this invention is N-[2-amino-4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester, also referred to as retigabine.
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- Pharmaceutically active 1,2,4-triamino-benzene derivatives, processes for their preparation and pharmaceutical compositions containing them
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Pharmacologically active 1,2,4-triaminobenzene derivatives of the General Formula I: STR1 where the symbols R1' R2' R3' R4' R5' Ar and Alk have the following meanings: where the symbols R1, R2, R3, R4, R5, Ar and Alk have the following meanings: R1 : hydrogen, C1 -C6 -alkyl, C2 -C6 -alkanoyl or the radical Ar; R2 : hydrogen or C1 -C6 -alkyl; R3 : C1 -C6 -alkoxy, NH2, C1 -C6 -alkylamino, C1 -C6 -dialkylamino, amino substituted by the radical Ar, C1 -C6 -alkyl, C2 -C6 -alkenyl, C2 -C6 -alkynyl, the radical Ar or the radical ArO--; R4 : hydrogen, C1 -C6 -alkyl or the radical Ar; R5 : hydrogen or C1 -C6 -alkyl or the radical Ar; Alk: a straight or branched alkylene group containing 1-9 carbon atoms, which can also be substituted by the radical Ar.
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