6294-52-6Relevant articles and documents
Iodine-catalyzed amination of benzothiazoles with KSeCN in water to access primary 2-aminobenzothiazoles
Zhu, Yu-Shen,Shi, Linlin,Fu, Lianrong,Chen, Xiran,Zhu, Xinju,Hao, Xin-Qi,Song, Mao-Ping
supporting information, p. 1497 - 1500 (2021/09/09)
A facile and sustainable approach for the amination of benzothiazoles with KSeCN using iodine as the catalyst in water has been disclosed under transition-metal free conditions. The reaction proceeded smoothly to afford various primary 2-amino benzothiazoles in up to 96% yield. A series of control experiments were performed, suggesting a ring-opening mechanism was involved via a radical process. This protocol provides efficient synthesis of primary 2-aminobenzothiazoles
Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases
Millies, Benedikt,Von Hammerstein, Franziska,Gellert, Andrea,Hammerschmidt, Stefan,Barthels, Fabian,G?ppel, Ulrike,Immerheiser, Melissa,Elgner, Fabian,Jung, Nathalie,Basic, Michael,Kersten, Christian,Kiefer, Werner,Bodem, Jochen,Hildt, Eberhard,Windbergs, Maike,Hellmich, Ute A.,Schirmeister, Tanja
, p. 11359 - 11382 (2019/12/24)
The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the molecules were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modification of the obtained cysteine mutants with maleimides, followed by computational elucidation of the possible binding modes. In infected cells, antiviral activity against Dengue virus serotype 2 using prodrugs of the inhibitors was observed. In summary, a novel inhibitor scaffold targeting an allosteric site shared between flaviviral NS2B/NS3 proteases is presented whose efficacy is demonstrated in vitro and in cellulo.
Novel Triapine Derivative Induces Copper-Dependent Cell Death in 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
, p. 3107 - 3121 (2019/04/01)
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.
