- Benzisothiazole compound and preparation method thereof and purpose of benzisothiazole compound for treating depression
-
The invention discloses a benzisothiazole compound and a preparation method thereof and a purpose of the benzisothiazole compound for treating depression. The benzisothiazole compound has a structureshown as a formula I. The research found that the compound in the formula I or its medicinal salt has the following good medicine properties of 5-HT1A acceptor excitement and 5-HT/NE reuptake inhibition effect, and has strong and rapid anti-depression effect in an animal depression model. The research result shows that the compound shown in the formula I or its medicinal salt can be used for treating depression. The invention provides an effective technical means for efficiently and rapidly treating the depression.
- -
-
Paragraph 0054; 0056; 0062; 0063
(2018/09/12)
-
- A key intermediate for the preparation of ziprasidone
-
The present invention relates to a ziprasidone key intermediate preparation method, wherein benzo[d]isothiazole-3-ol (or one) is adopted as a raw material, and reacts with a substituted sulfonyl chloride or anhydride under an alkaline condition to obtain benzo[d]isothiazole-3-substituted sulfonate, and the benzo[d]isothiazole-3-substituted sulfonate reacts with piperazine to prepare the ziprasidone key intermediate 3-(1-piperazinyl)-1,2-benzoisothiazole. The method of the present invention has characteristics of simple operation, easily available raw materials, less byproducts, simple post-treatment, less industrial three-waste and the like, and is especially suitable for industrial production.
- -
-
Paragraph 0105; 0108; 0109
(2018/04/03)
-
- Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents
-
Synthesis of 3-(4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)piperazin-1-yl) benzoisothiazole derivatives (5a-i), which constitute a new class of isoxazolines, has been accomplished in regio-selective manner. These derivatives have been prepared by employing the reaction between substituted aldoximes (4a-i) and 3-(4-Allylpiperazin-1-yl) benzoisothiazole in presence of chloramine-T which afforded in good yields. These compounds were screened for cytotoxic activity on tumor cells. Four among the nine synthesized compounds were found to exhibit potent cytotoxic and antineoplastic activities in comparison to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in mammalian cancer cells. The rest of the derivatives showed moderate activity.
- Byrappa, Sathish,Harsha Raj,Kungyal, Tenzin,Kudva N, Narayana U.,Salimath, Bharathi P.,Lokanatha Rai
-
p. 218 - 224
(2016/11/23)
-
- Aralkylpiperidine (or piperazinecarboxylic) and its derivatives used for treating hypercalcemia schinzopherenia
-
PROBLEM TO BE SOLVED: To provide an agent for treating schizophrenia and related neuropsychiatric diseases.SOLUTION: This invention provides an aralkylpiperidine (or piperazine) derivative represented by formula (1), where A ring is a 5-7 membered heterocycle including N, with the heterocycle including a hetero atom arbitrarily selected from O, S, N; X is O, an amino group or a substituted amino group; Z is CH, N or C; Y is O, N or S; n is an integer of 1-5; and R1-R6 are H, a C1-C4 alkyl group or the like.
- -
-
Paragraph 0116
(2018/12/01)
-
- An efficient synthesis and biological screening of benzofuran and benzo[d]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition
-
A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 ± 0.23 μM, 0.42 ± 0.23 against MTB DNA gyrase, MTB MIC of 3.64 μM, and was not cytotoxic in eukaryotic cells at 100 μM. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 °C in differential scanning fluorimetric evaluations.
- Reddy, Kummetha Indrasena,Srihari, Konduri,Renuka, Janupally,Sree, Komanduri Shruthi,Chuppala, Aruna,Jeankumar, Variam Ullas,Sridevi, Jonnalagadda Padma,Babu, Kondra Sudhakar,Yogeeswari, Perumal,Sriram, Dharmarajan
-
p. 6552 - 6563
(2015/02/18)
-
- INTERMEDIATE COMPOUNDS AND PROCESS FOR THE PREPARATION OF LURASIDONE AND SALTS THEREOF
-
The present invention relates to a process for the preparation of Lurasidone or a pharmaceutically acceptable salt thereof, a compound useful for the treatment of schizophrenia and bipolar disorder. The present invention further relates to processes for the preparation of Lurasidone intermediates, and to certain novel intermediates obtained by such processes.
- -
-
Page/Page column 22; 23
(2013/03/26)
-
- ARALKYL SUBSTITUTED PIPERIDINE OR PIPERAZINE DERIVATIVES AND THEIR USE FOR TREATING SCHIZOPHRENIA
-
The present invention discloses an aralkyl substituted piperidine or piperazine derivative and the use of the derivative in preparation of medicaments for treating schizophrenia and correlative psychoneuroses. It is shown by pharmacological tests that the derivative of the present invention has better antischizophrenic effect and less toxicity. Said derivative is a free base or salt of the compound having the following general formula.
- -
-
Page/Page column 21
(2011/06/10)
-
- ARYLPIPERAZINE-CONTAINING PYRROLE 3-CARBOXAMIDE DERIVATIVES FOR TREATING DEPRESSIVE DISORDERS
-
The present invention relates to novel arylpiperazine-containing pyrrole 3-carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof which is useful for preventing or treating depressive disorders. The present invention also provides a method for preparing the arylpiperazine-containing pyrrole 3-carboxamide derivatives or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing same, and a method for preventing or treating depressive disorders.
- -
-
Page/Page column 54-55
(2010/04/27)
-
- Heterocyclic Derivatives and Their Use as Strearoyl-Coa Desaturase Inhibitors
-
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where x, y, G, J, K, L, M, W, R2, R3, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
- -
-
Page/Page column 15
(2008/12/05)
-
- Ziprasidone process
-
A process for preparing ziprasidone having low levels of keto ziprasidone and hydroxy ziprasidone impurities.
- -
-
Page/Page column 6-7
(2008/06/13)
-
- Process for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1piperazinyl) ethyl)-6-chloro-1, 3-dihydro-2h-indol-2-one hydrochloride (ziprasidone hydrochloride) and its intermediate
-
The present invention relates to improved processes for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one and its hydrochloride, which is known as Ziprasidone hydrochloride of Formula (I) and 5-(2-Chloro acetyl)-6-chloro oxindole of Formula (IV), which is an intermediate for the preparation of 5-(2-chloro ethyl)-6-chloro oxindole of Formula (V). Ziprasidone hydrochloride of Formula (I) of the present invention is depicted by the following structure.
- -
-
-
- Fast atom bombardment-promoted reductive ring opening of 1,2-benzisothiazoles
-
Fast atom bombardment mass spectral examination of molecules containing a 1,2-benzisothiazole ring, using a thiol reducing agent matrix, promotes reductive ring opening of the benzisothiazole ring, giving an [M+H]+ two daltons higher than expected. Measurements using a non-reducing matrix produce the expected [M+H]+. This is a general phenomenon, observed with a number of molecules containing the benzisothiazole ring. The ring-opened structure has been confirmed by chemical synthesis and observed in metabolic studies.
- Sharp, Thomas R.,Lambert, John F.,Walinsky, Stanley W.
-
p. 2117 - 2120
(2007/10/03)
-
- 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.
- -
-
-
- 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.
- -
-
-
- Processes for producing isothiazole derivatives
-
A method for producing a 1,2-benzisothiazole characterized by treating a 2-(alkylthio)benzaldehyde oxime with a halogen compound; a method for producing a 3-halo-1,2-benzisothiazole characterized by treating a 1,2-benzisothiazole with a halogenating agent; and a method for producing a 1-(1,2-benzisothiazol-3-yl)piperazine characterized by reacting the obtained 3-halo-1,2-benzisothiazoles with a piperazine. By the method of the present invention, 1,2-benzisothiazoles and 3-halo-1,2-benzisothiazoles, which are useful as intermediates for pharmaceutical compositions such as psychotropic agents, and 1-(1,2-benzisothiazole-3-yl)piperazines synthesized therefrom can be obtained in a high yield without using expensive starting materials by shorter and simpler process than conventional methods.
- -
-
-
- 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.
- -
-
-
- Cyanobenzenesulfenyl halide and process for preparation of 3-substituted benzisothiazole using the same
-
The present invention provides a compound represented by the general formula (I): STR1 wherein X represents Cl or Br, a process for preparation of the same and a process for preparation of 3-substituted benzisothiazole by reaction of the compound (I) with a piperazine compound.
- -
-
-
- Succinimide derivatives. II. Synthesis and antipsychotic activity of N- [4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]1,2-cis- cyclohexanedicarboximide (SM-9018) and related compounds
-
Cyclic imides bearing ω-(4-benzisothiazol-3-yl-1-piperazinyl)alkyl moieties were synthesized and tested for antipsychotic activity. The in vitro binding affinities of these compounds were examined for dopamine 2 (D2) and serotonin 2 (5-HT2) receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, N-[4-[4-(1,2- benzisothiazol-3-yl)-1-piperazinyl]butyl]-1,2-cis-cyclohexanedicarboximide (SM-9018), was found to be more potent and more selective in vivo than tiospirone in its antipsychotic activity. SM-9018 (17) is currently undergoing clinical evaluation as a selective antipsychotic agent.
- Ishizumi,Kojima,Antoku,Saji,Yoshigi
-
p. 2139 - 2151
(2007/10/03)
-
- 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.
- Yevich, Joseph P.,New, James S.,Smith, David W.,Lobeck, Walter G.,Catt, John D.,et al.
-
p. 359 - 369
(2007/10/02)
-
- ANALGESIC 1,2-BENZISOTHIAZOL-3-YLPIPERAZINE DERIVATIVES
-
A series of non-opiate analgesics of Formula I STR1 wherein R 1 is hydrogen, alkyl, aralkyl, or aryloxyalkyl; R 2 is alkyl or hydrogen; and R 3 and R 4 are independently selected from hydrogen, alkyl, acyloxy, alkoxy, alkylthio, halogen, hydroxyl, or trifluoromethyl; or a pharmaceutically acceptable acid addition salt.
- -
-
-
- 1,2,4-TRIAZOL-3-ONE ANTIDEPRESSANTS
-
Phenoxyalkyl substituted-1,2,4-triazolones having anti-depressant properties typified by 2-3-4-(3-chlorophenyl)-1-piperazinyl!propyl!-5-ethyl-4-(2-phenoxyethyl)-2H-1,2, 4-triazol-3(4H)-one are disclosed.
- -
-
-