7716-66-7Relevant articles and documents
Unexpected ring-expansion of 1,2-benzisoxazol-3-ones
Raw, Steven A.,O'Kearney-Mcmullan, Anne M.,Graham, Mark A.
, p. 6775 - 6778 (2011)
A novel and unexpected ring-expansion reaction of 1,2-benzisoxazol-3-ones is identified. The scope of this reaction is exemplified and the proposed mechanism is also implicated in another degradation process. This reaction also represents a new method for accessing the 4H-1,3-benzoxazin-4-one skeleton.
Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents
Byrappa, Sathish,Harsha Raj,Kungyal, Tenzin,Kudva N, Narayana U.,Salimath, Bharathi P.,Lokanatha Rai
, p. 218 - 224 (2017)
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.
Dimer impurity in ziprasidone hydrochloride raw material and preparation method thereof
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Paragraph 0133; 0137-0139, (2021/06/09)
The invention provides a dimer impurity in a ziprasidone hydrochloride raw material. The dimer impurity has a structure as shown in a formula 1. According to the invention, research and experiment are carried out from the mechanism direction, and it is believed that the compound 3-chloro-1, 2-benzothiazole can be subjected to self-condensation in the reaction process to generate the dimer impurity with the structure as shown in the formula 1. The impurity has extremely poor solubility and is slightly soluble in dimethyl sulfoxide or dichloromethane. The 3-chloro-1, 2-benzothiazole dimer impurity can be remained in the API without being controlled and removed, so the control of the dimer impurity in the preparation process of the 3-chloro-1, 2-benzothiazole and the anhydrous piperazine is particularly important. The invention further provides a preparation method for obtaining the high-purity ziprasidone hydrochloride dimer impurity, and the method is simple, high in controllability and mild in condition. The ziprasidone hydrochloride pharmaceutical composition can be used for ziprasidone hydrochloride process research and development, production, quality standard establishment and quality control links, and provides technical support for ziprasidone hydrochloride medication safety.
Discovery of a Potent and Orally Bioavailable Hypoxia-Inducible Factor 2α (HIF-2α) Agonist and Its Synergistic Therapy with Prolyl Hydroxylase Inhibitors for the Treatment of Renal Anemia
Yu, Yancheng,Yang, Fulai,Yu, Quanwei,Liu, Simeng,Wu, Chenyang,Su, Kaijun,Yang, Le,Bao, Xiaoqian,Li, Zhihong,Li, Xiang,Zhang, Xiaojin
, p. 17384 - 17402 (2021/11/16)
Activation of hypoxia-inducible factor 2 (HIF-2) has emerged as a potent renal anemia treatment strategy. Here, the benzisothiazole derivative 26 was discovered as a novel HIF-2α agonist, which first demonstrated nanomolar activity (EC50 = 490 nM, Emax = 349.2%) in the luciferase reporter gene assay. Molecular dynamics simulations indicated that 26 could allosterically enhance HIF-2 dimerization. Furthermore, compound 26 had a good pharmacokinetic profile (the oral bioavailability in rats was 41.38%) and an in vivo safety profile (the LD50 in mice was greater than 708 mg·kg-1). In the in vivo efficacy assays, the combination of 26 and the prolyl hydroxylase inhibitor, AKB-6548, was confirmed for the first time to synergistically increase the plasma erythropoietin level in mice (from 260 to 2296 pg·mL-1) and alleviate zebrafish anemia induced by doxorubicin. These results provide new insights for HIF-2α agonists and the treatment of renal anemia.
Benzisothiazole compound and preparation method thereof and purpose of benzisothiazole compound for treating depression
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Paragraph 0054; 0056; 0060; 0061, (2018/09/12)
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.
An Aryne-Based Route to Substituted Benzoisothiazoles
Chen, Yiding,Willis, Michael C.
, p. 4786 - 4789 (2015/10/12)
The combination of arynes, generated using fluoride from the corresponding 2-(trimethylsilyl)aryl triflates, and 3-hydroxy-4-aminothiadiazoles leads to the selective formation of 3-amino-substituted benzo[d]isothiazoles. Variation of the substitution pattern of the aryne precursor, and of the thiadiazole, is possible, with the target heterocycles being obtained in good to excellent yields. In all cases, use of 3-hydroxy-4-aminothiadiazoles leads to incorporation of the amino-substituent in the product heterocycle.
METHOD FOR PRODUCING 3-HALO-1,2-BENZISOTHIAZOLES
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Page/Page column 2-3, (2013/02/28)
A method for producing a 3-halo-1,2-benzisothiazole represented by the general formula (2): wherein R1 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, a nitro group or a halogen atom, and X is a halogen atom, the method characterized by reacting a 1,2-benzisothiazol-3-one represented by the general formula (1): wherein R1 is the same group as the R1 defined in the above general formula (2), with a thionyl halide in a polar solvent. The 3-halo-1,2-benzisothiazole obtainable according to the method of the present invention is suitably used as production raw materials and the like for a medicament and the like.
Effect of nitro-substituton on the photochemistry of 3-piperidino-1,2-benzisothiazole derivatives: A mechanistic investigation
Tanikawa, Hiroharu,Ishii, Kazuhiro,Kubota, Shun,Sasanuma, Takashi,Yagai, Shiki,Kitamura, Akihide,Karatsu, Takashi
experimental part, p. 659 - 674 (2010/09/07)
Photochemical isomerization of 3-piperidino-1,2-benzisothiazole (BIT)-benzothiazole (BT) was investigated. In particular, the effect of nitro-substitution on the benzene ring was selectively examined for the parent, 5-nitro-, and 7-nitro-derivatives. 3-Piperidino-BIT and nitro-3-piperidino-BIT isomerized irreversibly to the corresponding 2-piperidino-BT, and this reaction mechanism was investigated using density-functional theory (DFT) and time-dependent (TD)-DFT calculations. These calculations showed that this isomerization goes through an azirine intermediate. In addition, excitation wavelength effect demonstrates that isomerization occurs from the upper excited state of nitro-derivatives. The HOMO-LUMO transition has charge-transfer and photoinactive characters.
Process for preparing 3-chlorobenzisothiazoles
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, (2008/06/13)
N-Unsubstituted 3-chlorobenzisothiazoles are obtained by reacting N-unsubstituted benzisothiazolones with phosgene in the presence of catalysts.
Processes for producing isothiazole derivatives
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, (2008/06/13)
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.
