- Preparation method of ziprasidone intermediate
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The invention relates to a preparation method of a ziprasidone intermediate.The preparation method is a method to prepare 6-chloro-2-indolone by one-pot process, an alkali liquid and phase-transfer catalyst low in price are used in the preparation process to substitute the prior art sodium hydride necessary to use and high in price, recyclable low-grade aliphatic ketone and low-grade fatty alcohol are used to substitute DMF (dimethyl formamide) and DMSO (dimethylsulfoxide) difficult to recycle, the cost is reduced greatly, the materials used herein are cheap and easy to obtain, the process is simple and feasible, posttreatment steps are simplified, particularly the step (1) requires no washing, extracting and purifying operation, one step may be performed directly, the whole operating step needs no use of column chromatography for purification, the whole preparation process is simplified, and the method is convenient to industrialize; in the synthetic process of formula III compound, a deacidifying process is mild and safe; in the synthesis of formula II compound, low-valence sulfur-containing compound is used in reduction, generation of mass waste acid liquid is avoided, production is safe and environment-friendly, and the preparation process is simple and easy.
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- NOVEL ARYL UREIDO BENZOIC ACID DERIVATIVES AND THEIR USE
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This invention relates to novel aryl ureido benzoic acid derivatives useful as selective and non-competitive antagonists of the ionotropic GluR5 receptor. Due to their biological activity, the aryl ureido derivatives of the invention are considered useful for treating diseases that are responsive to modulation of an aspartate or a glutamate receptor. Moreover the invention provides chemical compounds for use according to the invention, as well as pharmaceutical compositions comprising the chemical compounds, and methods of treating diseases or disorders or conditions responsive to modulation of an aspartate or a glutamate receptor.
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- Bioisosteric modifications of 2-arylureidobenzoic acids: Selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5
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2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 μM, respectively, compared to compound 2a with IC50 = 4.8 μM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.
- Valgeirsson, Jon,Nielsen, Elsebet ?.,Peters, Dan,Mathiesen, Claus,Kristensen, Anders S.,Madsen, Ulf
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p. 6948 - 6957
(2007/10/03)
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- Method for producing oxyindoles
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There is disclosed a method for producing oxyindoles, which comprises reacting a 2-halogenophenylacetic acid or its salt with ammonia in the presence of a copper salt catalyst, and heating a mixture of the produced 2-aminophenylacetic acid or its salt and oxyindoles in the presence of an acid catalyst, to subject the 2-aminophenylacetic acid or its salt to a ring-closure reaction. According to this method, relatively readily available 2-halogenophenylacetic acids are used as a starting raw material to industrially produce highly pure oxyindoles in high yield in one pot without involving complicated steps. Further, since the amination is carried out at a temperature greatly lower than that of the conventional art, the lowering of the pH of the reaction liquid can be suppressed. Therefore, the restrictions on the specifications of the reaction apparatus, such as corrosion prevention and pressure resistance, can be mitigated.
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- Method for producing oxyindoles
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There is disclosed a method for producing oxyindoles, which comprises reacting a 2-halogenophenylacetic acid or its salt with ammonia in the presence of a copper salt catalyst, and heating a mixture of the produced 2-aminophenylacetic acid or its salt and oxyindoles in the presence of an acid catalyst, to subject the 2-aminophenylacetic acid or its salt to a ring-closure reaction. According to this method, relatively readily available 2-halogenophenylacetic acids are used as a starting raw material to industrially produce highly pure oxyindoles in high yield in one pot without involving complicated steps. Further, since the amination is carried out at a temperature greatly lower than that of the conventional art, the lowering of the pH of the reaction liquid can be suppressed. Therefore, the restrictions on the specifications of the reaction apparatus, such as corrosion prevention and pressure resistance, can be mitigated.
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