- An efficient one-pot synthesis of 2-aminobenzothiazoles from substituted anilines using benzyltrimethylammonium dichloroiodate and ammonium thiocyanate in DMSO:H2O
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Treatment of a variety of substituted anilines with benzyltrimethylammonium dichloroiodate (1.2 equiv) and ammonium thiocyanate (1.0 equiv) in DMSO:H2O (9:1) at 70 °C gave the corresponding 2-aminobenzothiazoles in excellent isolated yields (75–97%; ave. yield for all substrates = 90%). The reaction worked well for 2(4)-mono-, 2,4-di-, or 3,4,5-tri-substituted anilines, and a wide range of both electron donating groups (MeO, HO, CF3O, Me) and electron withdrawing groups (NO2, CN, CO2Et, CO2H, Cl, F) were well tolerated. This method provides a useful alternative to other methods that are either less efficient (requiring 3–7 fold equivalents of reagents) or utilize highly toxic and corrosive liquid Br2 as the oxidizing agent.
- Dass, Reuben,Peterson, Matt A.
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supporting information
(2021/10/04)
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- Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
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Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
- Chen, Ge,Niu, Chunyi,Yi, Jianhua,Sun, Lin,Cao, Hengyi,Fang, Yanjia,Jin, Taijie,Li, Ying,Lou, Chunli,Kang, Jingwu,Wei, Wanguo,Zhu, Jidong
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- Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
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Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
- Chen, Ge,Niu, Chunyi,Yi, Jianhua,Sun, Lin,Cao, Hengyi,Fang, Yanjia,Jin, Taijie,Li, Ying,Lou, Chunli,Kang, Jingwu,Wei, Wanguo,Zhu, Jidong
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p. 3107 - 3121
(2019/04/01)
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- Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance
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A series of 18β-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant.
- Jin, Le,Huang, Rizhen,Huang, Xiaochao,Zhang, Bin,Ji, Min,Wang, Hengshan
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p. 1759 - 1775
(2018/03/01)
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- IMIDAZO[2,1-B]THIAZOLE AND 5,6-DIHYDROIMIDAZO[2,1-B]THIAZOLE DERIVATIVES USEFUL AS S100-INHIBITORS
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A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful for use in the treatment of cancer, an inflammatory disorder,an autoimmunity disorder or a neurodegenerative disorder.
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Page/Page column 84; 87
(2016/04/09)
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- Design, synthesis and biological evaluation of benzimidazolyl and benzothiazolyl picolinamide derivatives as antimicrobial agents
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A series of benzothiazolyl amides and benzimidazolyl amides (6a-f) has been synthesized from the coupling reaction of substituted picolinic acid with benzothiazole and benzimidazoles, respectively. The newly synthesized compounds were evaluated for their efficacy as antimicrobial agents against various Gram-positive and Gram-negative strains of bacteria and fungal strains. Amongst these compounds 6f was found to be the most potent against Bacillus subtilis and Candida albicans. Moreover, other compounds also found to be potential antibacterial agents in comparison to the standard drugs.
- Namani, Vasu,Bharath Kumar Goud,Bharathi Kumari,Kumbham, Ramesh,Balakrishna, Kannoju,Bhima, Bhukya
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p. 4575 - 4578
(2015/11/27)
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- SYNTHESIS OF 2-AMINO-3-FLUOROBENZENETHIOL AND ITS CONVERSION INTO DIFFERENT HETEROCYCLES
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Heterocycles containing fluorine possess a variety of biological applications and are useful drugs. 5-Fluorouracil and 5-fluorotryptamine are eefective drugs used in the treatment of cancer.
- Gupta, R. R.,Kumar, Rakesh
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p. 229 - 240
(2007/10/02)
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