- Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid
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(S)-4-Amino-4,5-dihydro-2-thiophenecarboxylic acid ((S)-6) was previously synthesized (Adams, J. L.; Chen, T. M.; Metcalf, B. W. J. Org. Chem. 1985, 50, 2730-2736.) as a heterocyclic mimic of the natural product gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid), a mechanism-based inactivator of γ-aminobutyric acid aminotransferase (GABA-AT) (Rando, R. R. Biochemistry 1977, 16, 4604). Inactivation of GABA-AT by (S)-6 is time-dependent and protected by substrate. Two methods were utilized to demonstrate that, in addition to inactivation, about 0.7 equiv per inactivation event undergoes transamination. Inactivation results from the reaction of (S)-6 with the pyridoxal 5-phosphate (PLP) cofactor. The adduct was isolated and characterized by ultraviolet-visible spectroscopy, electrospray mass spectrometry, and tandem mass spectrometry. All of the results support a structure (11) that derives from the predicted aromatization inactivation mechanism (Scheme 2) originally proposed by Metcalf and co-workers for this compound. This is only the third example, besides gabaculine and L-cycloserine, of an inactivator of a PLP-dependent enzyme that acts via an aromatization mechanism.
- Fu, Mengmeng,Nikolic, Dejan,Van Breemen, Richard B.,Silverman, Richard B.
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- Crystal engineering of cadmium coordination polymers decorated with nitro-functionalized thiophene-2,5-dicarboxylate and structurally related bis(imidazole) ligands with varying flexibility
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A new thiophene-2,5-dicarboxylic acid derivative, 3-nitro-thiophene-2,5-dicarboxylic acid (H2ntdc), was synthesized. Reaction of H2ntdc with cadmium diacetate dihydrate and structurally related bis(imidazole) ligands with varying flexibility gave rise to four new CPs, formulated as {[Cd(ntdc)(bmip)(H2O)](H2O)}n (1), {[Cd(ntdc)(bmib)](H2O)}n (2), [Cd(ntdc)(beip)]n (3) and [Cd(ntdc)(beib)]n (4) [bmip = 1,3-bis(2-methylimidazolyl)propane, bmib = 1,4-bis(2-methylimidazolyl)butane, beip = 1,3-bis(2-ethylimidazolyl)propane and beib = 1,4-bis(2-ethylimidazolyl)butane]. Moreover, a new compound {[Cd(ntc)2(bmib)](H2O)}n (5) (Hntc = 4-nitro-thiophene-2-carboxylic acid) involving in situ ligand synthesis was prepared. Structural analyses reveal that 1 features a two-dimensional (2D) 44-sql layer, and is further stacked via hydrogen bonding interactions to give a three-dimensional (3D) hydrogen-bonded architecture. 2 displays a 3,4-connected 3D network with ins type topology, which is composed of 2D hcb topological networks pillared by the bmib ligands. 3 exhibits a 3,5-connected 3D network with a (42·63·85)(42·6) topology. 4 possesses a 3-fold interpenetrating 3D net with a dmp topology. 5 can be described as a one-dimensional (1D) chain structure, and is further assembled into a 2D hydrogen-bonded 44sql layer. Factors that influence the structural assembly of 1-4, as well as the formation of 5 involving the in situ produced Hntc ligand, are discussed. Moreover, structure stabilities and photoluminescence properties of the complexes were also investigated.
- Xue, Li-Ping,Li, Zhao-Hao,Ma, Lu-Fang,Wang, Li-Ya
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- Method for rapidly preparing 4-nitrothiophene-2-formic acid based on microchannel reaction technology
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The invention discloses a method for rapidly preparing 4-nitrothiophene-2-formic acid based on a micro-channel reaction technology. The method involves a nitration reaction. The method specifically comprises the following steps of: continuously pumping a sulfuric acid solution of thiophene-2-formic acid and nitric acid or nitric acid and sulfuric acid mixture into a micro-channel reactor through a sample injection pump according to a certain equivalent proportion, and performing mixing; and carrying out an electrophilic substitution reaction of nitroacyl cations on thiophene rings at a certain temperature to generate the product 4-nitrothiophene-2-formic acid. By applying the microchannel reaction technology, the synthetic method which is safer, more efficient, simple and convenient to operate and low in cost is provided, and the high-conversion-rate product 4-nitrothiophene-2-formic acid is obtained under the controllable continuous condition of the nitration reaction.
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Paragraph 0007; 0011-0012
(2021/11/21)
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- Raltitrexed pharmaceutical composition and preparation method thereof
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The invention relates to a raltitrexed pharmaceutical composition which is high in safety and a preparation method thereof. The raltitrexed pharmaceutical composition comprises raltitrexed and thiophene related substances, wherein the content of the thiophene related substances is not higher than 0.3%. The raltitrexed pharmaceutical composition is good in safety, effectiveness and stability and can relieve the blood toxicity of the raltitrexed to a certain degree.
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Paragraph 0049; 0050
(2018/04/02)
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- Impurity B of raltitrexed, and preparation method and application thereof
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The invention discloses a potential blood system toxic impurity B of raltitrexed, a preparation method thereof, and a use of the impurity B as an impurity reference substance.
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Paragraph 0019; 0040; 0041; 0057; 0072; 0087
(2018/03/01)
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- ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS
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The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
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Page/Page column 38-39
(2010/04/06)
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- Carbapenem antibiotic compounds
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The present invention relates to carbapenems and provides a compound of the formula (I) STR1 wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C1-4 alkyl; R3 is hydrogen or C1-4 alkyl; and the thienyl ring is optionally further substitued by one or two substituents selected from halo, cyano, C1-4 alkyl, nitro, hydroxy, carboxy, C1-4 alkoxy, trifluoromethyl, C1-4 alkoxycarbonyl, amino, C1-4 alkylamino, di-C1-4 alkylamino, sulfonic acid, C1-4 alkylS(O)n -- (wherein n is 0-2), C1-4 alkanoylamino, C1-4 alkanoyl(N-C1-4 alkyl)amino, carbamoyl, C1-4 alkylcarbamoyl, di-C1-4 alkylcarbamoyl and N-C1-4 alkanesulfonamido; or by a tetramethylene group attached to adjacent carbon atoms on the thienyl ring; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them are also described.
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- Antibiotic penem compounds
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The present invention provides a compound of the formula (I) STR1 wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C1-4 alkyl; Z is carboxy, sufonic acid, tetrazol-5-yl or C 1-4 alkylsulfonylcarbamoyl (--CONHSO2 C1-4 alkyl); A is a phenyl or thienyl ring; and A is optionally further substituted by one or two substituents or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.
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- THE PREPARATION OF 2-(HETEROCYCLIC)THIENOPYRIDINE DERIVATIVES
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The preparation of a series of 2-(heterocyclic)-4-ethyl-4,7-dihydro-7-oxothienopyridine-6-carboxylic acids (5j-l) by aminolysis of the corresponding 2-bromo derivative (5i) is described.None of the compounds (5j-l) showed any interesting antibacterial activity.
- Elliot, Richard, L.,O'Hanlon, Peter J.,Rogers, Norman H.
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p. 3295 - 3302
(2007/10/02)
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- Factors controlling the Selectivity of ipso-Attack in Homolytic Aromatic Substitutions. Reactions of Alkyl Radicals with Nitrothiophen Derivatives
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The reactions of the nearly electroneutral methyl and of the nucleophilic 1-adamantyl radical with some selected nitrothiophen derivatives have been investigated in order to elucidate the factors which control the positional selectivity of radical addition to an aromatic substrate.With 5-nitro-2-X-thiophens (II), (V), and (VI) and 3,5-dinitro-2-methoxycarbonylthiophen (III) the adamantyl radical gave exclusively the products of ipso-attack, whereas the methyl radical selectively added at the unsubstituted 4-position.On the other hand, with 4-nitro-2-methoxycarbonylthiophen (I) both radicals added at the 5-position and with 4,5-dinitro-2-methoxycarbonylthiophen (IV) both radicals gave the products of ipso-substitution by displacing the nitro-group from the 5-position.These changes in positional selectivity are explained by assuming that the nature of the transition state of the addition step changes as a function of the polar character of the radical and of the electron deficiency of the aromatic substrates.
- Cogolli, Pietro,Maiolo, Filippo,Testaferri, Lorenzo,Tiecco, Marcello,Tingoli, Marco
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p. 1331 - 1335
(2007/10/02)
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