37052-78-1Relevant academic research and scientific papers
A new strategy for the synthesis of 2-mercaptobenzazole derivatives by green chemistry metrics
Vessally, Esmail,Monfared, Aazam,Eskandari, Zahra,Abdoli, Morteza,Hosseinian, Akram
supporting information, p. 1 - 5 (2020/08/25)
A green and efficient method has been developed for the synthesis of 2-mercaptobenzazole derivatives via the reaction of commercially available aniline derivatives with low-cost and nontoxic potassium thiocyanate in water. The reactions proceeded smoothly under catalyst- and ligand-free conditions to give the corresponding products in good to excellent yields. The versatility, low cost, and environmental friendliness, in combination with high yields and easy work-up makes the procedure noteworthy.
Method for continuous-flow synthesis of 2-sulfydryl-5-methoxybenzimidazole
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Paragraph 0034; 0039-0042; 0045-0047; 0050-0052; 0055-0057, (2021/07/17)
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for continuous-flow synthesis of 2-sulfydryl-5-methoxybenzimidazole. The method comprises the following reaction steps in a continuous flow reactor: (1) subjecting 2-nitro-4-methoxyaniline to reacting with a reducing agent under the action of a catalyst to obtain a reaction solution containing 4-methoxy o-phenylenediamine; and (2) enabling the reaction solution containing the 4-methoxy o-phenylenediamine to react with carbon disulfide so as to generate the 2-sulfydryl-5-methoxybenzimidazole. According to the production process improved by a continuous flow technology in the invention, reaction time is greatly shortened, operation is simple and convenient, production efficiency is improved, and the yield and the purity of the obtained product are very high. Therefore, the method disclosed by the invention has a very good application prospect in the synthesis of 2-sulfydryl-5-methoxybenzimidazole.
A new series of benzoxazole-based SIRT1 modulators for targeted therapy of non-small-cell lung cancer
Sever, Belgin,Akal?n ?ift?i, Gül?en,Alt?ntop, Mehlika Dilek
, (2020/09/21)
In an attempt to identify potential anticancer agents for non-small-cell lung cancer (NSCLC) targeting sirtuin 1 (SIRT1), the synthesis of a new series of benzoxazoles (3a – i) was carried out through a facile and versatile synthetic route. The compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cells using the MTT assay. 2-[(5-Nitro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3e) and 2-[(5-chloro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3g) were the most potent and selective anticancer agents in this series against the A549 cell line, with IC50 values of 46.66 ± 11.54 and 55.00 ± 5.00 μM, respectively. The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. Both compounds induced apoptosis in a dose-dependent manner. The effects of compounds 3e and 3g on SIRT1 activity were determined. On the basis of in vitro studies, it was observed that compound 3g caused a significant decrease in SIRT1 levels in a dose-dependent manner, whereas compound 3e increased the SIRT1 levels. According to molecular docking studies, the substantial alteration in the type of action could be attributed to the difference between the interactions of compounds 3e and 3g with the same residues in the active site of SIRT1 (PDB code: 4IG9). On the basis of in silico ADME (absorption, distribution, metabolism, and excretion) studies, these compounds are predicted to possess favorable ADME profiles. According to the in vitro and in silico studies, compounds 3e and 3g, small-molecule SIRT1 modulators, were identified as potential orally bioavailable anticancer agents for the targeted therapy of NSCLC.
Cinnamide derived pyrimidine-benzimidazole hybrids as tubulin inhibitors: Synthesis, in silico and cell growth inhibition studies
Sana, Sravani,Reddy, Velma Ganga,Srinivasa Reddy,Tokala, Ramya,Kumar, Rahul,Bhargava, Suresh K.,Shankaraiah, Nagula
, (2021/03/15)
An approach in modern medicinal chemistry to discover novel bioactive compounds is by mimicking diverse complementary pharmacophores. In extension of this strategy, a new class of piperazine-linked cinnamide derivatives of benzimidazole-pyrimidine hybrids have been designed and synthesized. Their in vitro cytotoxicity profiles were explored on selected human cancer cell lines. Specifically, structural comparison of target hybrids with tubulin-DAMA-colchicine and tubulin-nocodazole complexes has exposed a deep position of benzimidazole ring into the αT5 loop. All the synthesized compounds were demonstrated modest to interesting cytotoxicity against different cancer cell lines. The utmost cytotoxicity has shown with an amine linker of benzimidazole-pyrimidine series, with specificity toward A549 (lung cancer) cell line. The most potent compound in this series was 18i, which inhibited cancer cell growth at micromolar concentrations ranging 2.21–7.29 μM. Flow cytometry studies disclosed that 18i inhibited the cells in G2/M phase of cell cycle. The potent antitumor activity of 18i resulted from enhanced microtubule disruption at a similar level as nocodazole on β-tubulin antibody, explored using immunofluorescence staining. The most active compound 18i also inhibited tubulin polymerization with an IC50 of 5.72 ± 0.51 μM. In vitro biological analysis of 18i presented apoptosis induction on A549 cells with triggering of ROS generation and loss of mitochondrial membrane potential, resulting in DNA injury. In addition, 18i displayed impairment in cellular migration and inhibited the colony formation. Notably, the safety profile of most potent compound 18i was revealed by screening against normal human pulmonary epithelial cells (L132: IC50: 69.25 ± 5.95 μM). The detailed binding interactions of 18i with tubulin was investigated by employing molecular docking, superimposition and free energy analyses. Thus remarks made in this study established that pyrimidine-benzimidazole hybrids as a new class of tubulin polymerization inhibitors with significant anticancer activity.
Highly Diastereoselective Synthesis of Dihydro-benzoimidazo-[1,3]-thiazines via Electro-oxidative Selenocyclization of Thioallyl Benzoimidazoles
Halder, Atreyee,Mahanty, Kingshuk,Maiti, Debabrata,De Sarkar, Suman
supporting information, p. 3895 - 3899 (2021/10/23)
The current methodology reveals a green and proficient electro-oxidative tandem selenocyclization of thioallyl benzoimidazoles manufacturing selenylated dihydro-benzoimidazo-thiazine derivatives. Both C?Se and C?N bond formation were achieved via this mild protocol which exhibits good functional group tolerability affording an extensive range of substrate scope up to 96% isolated yields. Complete control over the regioselective formation of the six-membered heterocycle and stereoselective construction of the contiguous stereocenters was established. The practical electrochemical method operates in an undivided cell at ambient temperature without using any metal and external chemical oxidant.
Esomeprazole sodium and lyophilized preparation comprising same
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Paragraph 0047, (2019/03/28)
The invention provides esomeprazole sodium and a lyophilized preparation comprising the same. A preparation method of esomeprazole sodium includes following steps: 1), synthesizing an intermediate; 2), synthesizing esomeprazole sodium; 3), roughly preparing esomeprazole sodium; 4), finely preparing esomeprazole sodium. Esomeprazole sodium prepared by the method is higher in preparation accuracy and safer to use; the preparation process is easier to control, and step decomposition brings convenience to quality control of middle steps, so that ensuring of preparation accuracy of esomeprazole sodium is facilitated, and drug prepared from esomeprazole sodium is safer.
Identification and structural characterization of the stress degradation products of omeprazole using Q-TOF-LC-ESI-MS/MS and NMR experiments: Evaluation of the toxicity of the degradation products
Shankar,Borkar, Roshan M.,Udutha, Suresh,Kanakaraju,Sai Charan,Misra,Srinivas
, p. 7294 - 7306 (2019/05/24)
Omeprazole (OMP), a prototype proton pump inhibitor used for the treatment of peptic ulcers and gastroesophageal reflux disease (GERD), was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug undergoes degradation under acid, base, neutral hydrolysis and oxidative degradation conditions and forms a total of sixteen degradation products, which were characterized by LC-MS/MS experiments and accurate mass measurements. Oxidative degradation products (OMP-15 and OMP-16) were synthesized and confirmed by various NMR experiments. The cytotoxic effects of OMP-15 and OMP-16 were tested on normal human cells HEK 293 and NIH3T3 by MTT assay. Based on the cytotoxicity results, compared to the standard OMP, both OMP-15 and OMP-16 were found to have relatively weaker toxic effects towards normal cells. Further, the in silico toxicity of OMP and its degradation products (OMP-1 to OMP-16) was assessed by the ProTox-II prediction tool. OMP and OMP-8 are predicted to have carcinogenicity, OMP-7 to have hepatotoxicity and OMP-2, OMP-3, OMP-9, OMP-11, OMP-14 and OMP-16 to have immune system toxicity with a high confidence score. The drug, OMP-1, OMP-6, OMP-7, OMP-8, OMP-13 and OMP-15 are predicted to combine with the aryl hydrocarbon receptor (AhR) with a high probability score. Additionally, two different targets, amine oxidase A and prostaglandin G/H synthase 1, are predicted as toxicity targets for OMP, OMP-1, OMP-6, OMP-8, OMP-13, OMP-15 and OMP-16 with probable binding.
AlCl3-Promoted Synthesis of 2-Mercapto Benzoheterocycles by Using Sodium Dimethyldithiocarbamate as Thiocarbonyl Surrogate
Liu, Xing,Zhang, Shi-Bo,Dong, Zhi-Bing
, p. 5406 - 5411 (2018/10/20)
A simple, expeditious and high-efficiency synthetic method for the AlCl3-mediated one-pot preparation of 2-mercapto benzoheterocycles (2-mercapto benzothiazoles, benzoxazoles and benzimidazoles) is described. By the treatment of a series of S, O and N heteroatoms containing bifunctional molecules with sodium dimethyldithiocarbamate in AlCl3, the desired benzoheterocycles are obtained smoothly. The protocol can also be applied on the synthesis of a series of thiazolidine-2-thiones, imidazolidine-2-thiones. This novel synthetic approach has advantages such as ligand-free, high efficiency, short reaction time, readily available starting materials and simple experimental procedures.
2-substituted thioacetamide compound, and preparation method and application thereof
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Paragraph 0073; 0081; 0082; 0083, (2018/11/04)
The invention discloses a 2-substituted thioacetamide compound, and a preparation method and an application thereof. The structure of the 2-substituted thioacetamide compound is represented by formulaI, and R in the formula I is a C1-C3 alkoxy group, halogen or NR1R2, wherein R1 and R2 are H and a C1-C3 alkyl group independently. The compound can effectively inhibit protein-arginine methyltransferase 5, and can be used as a PRMT5 inhibitor.
