161798-01-2Relevant academic research and scientific papers
Design, synthesis, cytotoxic evaluation and molecular docking studies of novel thiazolyl α-aminophosphonates
Gundluru, Mohan,Badavath, Vishnu Nayak,Shaik, Haroon Yasmin,Sudileti, Murali,Nemallapudi, Bakthavatchala Reddy,Gundala, Sravya,Zyryanov, Grigory V.,Cirandur, Suresh Reddy
, p. 1139 - 1160 (2020/11/16)
Abstract: A new class of thiazolyl α-aminophosphonate derivatives was synthesized by one-pot Kabachnik–Fields reaction of ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate with various aryl amines and diethyl phosphite under solvent-free conditions using β-cyclodextrin supported sulfonic acid (β-CD-SO3H) as an efficient, reusable and heterogeneous solid acid catalyst. The products were obtained in good to excellent yields at shorter reaction time. All the title compounds were screened for cytotoxic activity against human breast cancer (MCF-7 and MDA-MB-231), prostate cancer (DU-145) liver cancer (HepG2) and HeLa cancer cell lines using sulfarodamine-B (SRB assay). Compounds (8b, –4OMe), (8h, –4NO2) and (8j, –2I, –4CF3) showed better anticancer activity when compared with standard drug Adriamycin. Further in-silico target hunting reveals the anticancer activity of the designed compounds by inhibiting DNA topoisomerase II. Graphical abstract: [Figure not available: see fulltext.].
New preparation method of febuxostat intermediate
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Paragraph 0084-0086, (2020/03/06)
The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.
Synthesis, molecular docking, DFT study of novel N-benzyl-2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamide derivatives and their antibacterial activity
Sam Daniel Prabu,Lakshmanan, Sivalingam,Thirumurugan,Ramalakshmi,Arul Antony
, p. 619 - 626 (2020/02/06)
A series of febuxostat based new chemical entities was synthesized using microwave method and characterized by NMR, mass and FT-IR spectral studies. Molecular docking of febuxostat amide nucleus substitution compounds 8c (-7.91kcal/mol), 8g (-7.94 kcal/mol) exhibiting high binding energy against ALK receptors. Theoretical investigation of MEPs, HOMO, LUMO and energy gap of HOMO-LUMO were calculated by B3LYP/6-31G method. Among the tested compounds, methoxy substituted compound 8g showed highest antibacterial activity against S. aereus and B. subtilis.
Method for synthesizing febuxostat and intermediate thereof
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Paragraph 0109-0184, (2020/05/02)
The invention relates to a method for synthesizing febuxostat and an intermediate thereof, specifically a method for synthesizing 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The method comprises the following steps: preparing 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate; enabling the product obtained in the step (a) to react in DMF (Dimethyl Formamide) in the presence of potassium carbonate and bromo-isobutane, adding water and ethyl acetate for extraction, concentrating to obtain an organic layer, and recrystallizing with DMF to obtain 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The invention also relates to 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester and 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazoleethyl formate and application thereof to the preparation of febuxostat. The method of the invention has excellent performance.
Febuxostat and intermediates and synthesis thereof
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Paragraph 0081-0156, (2020/05/09)
The invention relates to febuxostat and intermediates and synthesis thereof, in particular to a method for synthesizing 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate, which comprisesthe following operation steps: (1) adding a reactant 2-(4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate into a mixture of polyphosphoric acid and methanesulfonic acid, and uniformly stirring the materials; (2) adding a Darf reaction reagent hexamethylenetetramine into the reaction mixture while stirring, continuously reacting, and cooling; and (3) adding saturated brine ice, separating out solid, filtering, cleaning the solid with water to-be-neutral, and drying to obtain the product. The invention also relates to 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazole ethyl formate and to the usethereof for the preparation of febuxostat. The method has excellent performance.
Reaction-based ratiometric fluorescent probe for selective recognition of sulfide anions with a large Stokes shift through switching on ESIPT
Karmakar, Parthasarathi,Manna, Srimanta,Ali, Syed Samim,Guria, Uday Narayan,Sarkar, Ripon,Datta, Pallab,Mandal, Debasish,Mahapatra, Ajit Kumar
supporting information, p. 76 - 84 (2017/12/28)
An ESIPT-based, highly selective, ratiometric fluorescent probe BNPT has been synthesized and characterized, which shows turn-on fluorescence response in the presence of S2-, attributed to the removal of a protective 2,4-dinitrobenzene (DNB) moiety, and the resulting fluorescent product has been used for the selective detection of Zn2+. UV-vis and fluorescence spectroscopy analysis, and DFT and TDDFT calculations were carried out to understand the sensing mechanism. The probe BNPT displays a rapid response time and good sensitivity. The probe can detect quantitatively in a concentration range of 0-6.0 μM. The detection limit is 31.3 nM. The sensing ability of BNPT has been successfully applied in real water samples. Applicability as an in-field test kit has been demonstrated by sensing with a BNPT-coated TLC plate. The probe BNPT has been successfully used for visualization of intracellular environment in living cells. The uniqueness lies in the fact that starting with the probe BNPT, sensing can be achieved by two different mechanisms-first, by selective de-protection of the probe BNPT and second, by reacting with the Zn2+ ensemble with S2-.
Synthesis method of ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate
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Paragraph 0009; 0020; 0021; 0022; 0023; 0024; 0025-0027, (2017/08/28)
The invention discloses a synthesis method of ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate. The synthesis method comprises the steps that ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate and N,N-dimethylformamide generate a reaction by taking n-butyllithium as a catalyst and then react with glacial acetic acid to generate ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate. Due to the fact that urotropin is not adopted in the synthesis reaction process, allergenic factors possibly brought in the production process are reduced; meanwhile, the production method is simple and environmentally friendly, the product is high in purity and yield, the cost is reduced, the working efficiency is improved, and the synthesis method is suitable for industrialized production.
Benzthiazole-derived chromogenic, fluorogenic and ratiometric probes for detection of hydrazine in environmental samples and living cells
Mahapatra, Ajit Kumar,Karmakar, Parthasarathi,Manna, Srimanta,Maiti, Kalipada,Mandal, Debasish
, p. 1 - 12 (2016/11/18)
Benzothiazole-based chromogenic and ratiometric fluorescent chemodosimetric probes CD1 and CD2, were synthesized and characterized. The probes are designed in such a way that the excited state intramolecular proton transfer (ESIPT) of the benzothiazole moiety gets blocked. Upon treatment with hydrazine in organo-aqueous medium[DMSO: H2O; 2:1 (v/v)] at physiological pH, the aectyl protective group of probes CD1 and CD2 were removed readily in presence hydrazine and ESIPT of the probes were switched on, which resulted remarkable photo-physical changes. These two ESIPT–based ratiometric fluorescent probes were shown to be selective and sensitive for hydrazine among different cations, anions and amines studied in organo-aqueous medium[DMSO: H2O; 2:1 (v/v)] at physiological pH, by fluorescence, absorption, and visual emission color change. These key features allows the two probes to be employed for hydrazine detection by simple visual inspection. DFT and TDDFT calculations were performed in order to demonstrate the sensing mechanism and the electronic properties of probe and hydrazinolysis product. An easy-to-prepare test strips, obtained by dipping the TLC plates into the solution of CD1 and CD2, were able to detect hydrazine in practical samples. Moreover, the utility of the probes CD1 in showing the hydrazine recognition in live cells has also been demonstrated using Vero cells as monitored by fluorescence imaging.
2 - (3 - aldehyde - 4 - isobuoxy phenyl) - 4 - methyl thiazole - 5 - carboxylic acid ethyl ester
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, (2017/08/25)
The invention provides a method for synthesizing high-purity ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate. The method comprises the following steps of carrying out thioacylation reaction on p-cyanophenol and thioacetamide as starting materials to obtain 4-hydroxythiobenzamide (II), directly carrying out thiazole reaction on the reaction product which is not separated and separating to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazole formate (III); carrying out formylation reaction on the compound as shown in the formula (III) to obtain ethyl 2-(3-carbaldehyde-4-hydroxyphenyl)-4-methyl-5-thiazole formate (IV), directly carrying out isobutylation reaction on the reaction product which is not separated to obtain ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate (I) of which the purity is equal to or greater than 99% and the content is equal to or greater than 99%. The production process is optimized and thus the quality of the product is greatly improved and the high yield is achieved.
Method for controlling febuxostat intermediate impurity
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Paragraph 0007; 0008; 0009; 0010; 0011; 0012, (2017/06/29)
The invention relates to a method for controlling febuxostat intermediate impurity. The method comprises the following steps: adding reactants comprising ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate and urotropine (HMTA) to a strong electron withdrawing solvent while strong stirring, controlling the feeding amount of the HMTA, carrying out a complete reaction at 90-95 DEG C for 3-5 h, hydrolyzing the obtained reaction product, extracting the hydrolyzed product, concentrating the obtained extract, crystallizing the obtained concentrate, and centrifuging obtained crystals to obtain the intermediate ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate with the impurity diformylation content of 0.1% or less. Generation of the febuxostat intermediate impurity is inhibited through controlling the feeding mode, the feeding ratio, the reaction temperature and the reaction time, so the diformylation impurity content in the reaction system is effectively reduced, thereby the impurity content is controlled to be 0.1% or less, and the febuxostat intermediate content reaches 99.0% or above.
