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PRO-DRUGS OF 5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)ETHYL)-6-CHLORO-1,3-DIHYDRO-2H-INDOL-2-ONE

The present invention relates to a pro-drug of ziprasidone or pharmaceutically acceptable salts thereof, processes for its preparation, and pharmaceutical compositions and methods of treatment comprising said pro-drug.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile

Herein we describe a focused set of new arylpiperazine derivatives as potential broad-spectrum antipsychotics. The general structure contains a quinolinone-like moiety, an arylpiperazine moiety, and a five-atom linker. Among them, 7-(5-(4-(benzo[d]isothiazol-4-yl)piperazin-1-yl)pentyl)quinolin-2(1H)-one (S6) shows a promising preclinical profile. Compound S6, characterized by partial D2R agonism, 5-HT1AR agonism, 5-HT2AR antagonism, and blockade of SERT activities, was found to decrease psychosis- and depressive-like symptoms in rodents. The polypharmacological profile of S6 could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, S6 demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Processes and intermediates for preparing 3-(1-piperazinyl)-1,2-benzisothiazole

The present invention relates to processes for the preparation of 3-(1-piperazinyl)-1,2-benzoisothiazole or its pharmaceutically acceptable salt and to novel intermediates used in the process.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Patent, the author is and a compound is mentioned, HPLC of Formula: C11H14ClN3S, 3-Piperazinobenzisothiazole hydrochloride, introducing its new discovery. HPLC of Formula: C11H14ClN3S

PROCESS FOR THE PREPARATION OF ZIPRASIDONE (5-[2-[4-(1,2-BENZISOTHIAZOL-3-Y1)-1-PIPERAZINY1]ETHY1]-6-CHLORO-1,3-DIHYDRO-2H-INDOL-2-ONE)

The present invention provides a new and useful process for preparing 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one (ziprasidone) and methods for its purification. The process comprises the steps of: (i) mixing 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one with either a free base or salt form of 3-(1-piperazinyl)-1,2-benzoisothiazole, in the presence of an alkaline compound and a high-boiling polar organic solvent or mixture of high boiling polar organic solvents, (ii) heating the mixture and stirring for a sufficient amount of time to obtain ziprasidone formation, (iii) cooling the mixture, adding it to water and filtering off the product, (iv) adding water to the product and stirring the suspension, and (v) isolating crude ziprasidone.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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N-SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES

This invention relates to compounds of the formula 1 wherein R1, R2, R7, R8, R9, U, V, Z, A, W, X, M, E, L, T and D are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system and other disorders.

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BENZOPYRONE DERIVATIVE AND USE THEREOF

The present invention relates to the field of pharmaceutical chemistry, and in particular, to a benzopyrone derivative and a use thereof. The benzopyrone derivative is compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof. It has been found by experiments that, this type of compounds is useful in prevention or treatment of neuropsychical diseases.

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Isothiazole – Wikipedia,
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Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents

Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens. Structure-activity relationships within the series are discussed. Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests. It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound’s lack of typical neuroleptic-like effects in the rat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy. Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile. Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.

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Isothiazole – Wikipedia,
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ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES

Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

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Reference£º
Isothiazole – Wikipedia,
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Application of 87691-88-1, In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, Application of 87691-88-1, name is 3-Piperazinobenzisothiazole hydrochloride, introducing its new discovery.

Orally-effective, long-acting sorbitol dehydrogenase inhibitors: Synthesis, structure – Activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 ? 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for ?17 h, when administered orally at a single dose of 2 mg/kg/day.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Synthesis and Biological Evaluation of 1-(1,2-Benzisothiazol-3-yl)- and (1,2-Benzisoxazol-3-yl)piperazine Derivatives as Potential Antipsychotic Agents

Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens.Structure-activity relationships within the series are discussed.Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests.It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h.The compound’s lack of typical neuroleptic-like effects in therat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy.Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile.Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com