399-95-1Relevant academic research and scientific papers
A potent free fatty acid receptor 1 agonist with a glucose-dependent antihyperglycemic effect
Wang, Xuekun,Xu, Yurui,Feng, Shujun,Huang, Xinyu,Meng, Xia,Chen, Jiao,Guo, Leilei,Ge, Junliang,Zhang, Jikang,Chen, Jianmei,Cheng, Li,Gu, Kai,Zhang, Yu,Jiang, Qing,Ning, Xinghai
, p. 8975 - 8978 (2019)
We present a novel free fatty acid receptor 1 (FFA1) agonist, named PAFA, with a strong agonist potency (EC50 = 6.04 nM) and good serum stability. PAFA significantly stimulates insulin secretion in INS-1 cells in a glucose-dependent manner and exhibits high antihyperglycemic effects in db/db mice without adverse effects.
Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17Β-HSD10 with implications to Alzheimer’s disease treatment
Aitken, Laura,Benek, Ondrej,Chribek, Matej,Dolezal, Rafael,Gunn-Moore, Frank,Hrabinova, Martina,Hroch, Lukas,Jun, Daniel,Kralova, Vendula,Kuca, Kamil,Lycka, Antonin,Musilek, Kamil,Prchal, Lukas,Schmidt, Monika,Vinklarova, Lucie,Zemanova, Lucie
, (2020/03/26)
Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson’s disease, or Alzheimer’s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1–2 μM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17β-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.
Regorafenib analogues and their ferrocenic counterparts: Synthesis and biological evaluation
Wilde, Myron,Arzur, Danielle,Baratte, Blandine,Lefebvre, Dorian,Robert, Thomas,Roisnel, Thierry,Le Jossic-Corcos, Catherine,Bach, Stéphane,Corcos, Laurent,Erb, William
supporting information, p. 19723 - 19733 (2020/12/04)
Approved by the FDA in 2012, regorafenib is one of the last chance treatments for colorectal cancer. While various analogues have already been prepared, ferrocenic derivatives have never been evaluated. In this study, we prepared various ferrocene-containing derivatives of regorafenib and recorded their biological activity in kinase and cellular assays. This led to the identification of a squaramide derivative which shows a good cellular activity and three ferrocene analogues with promising activity in both kinase and cellular assays. This journal is
A process for preparing auspicious standard phinney intermediates
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Paragraph 0007; 0014-0015; 0018-0019; 0024; 0029; 0034, (2019/05/06)
The invention discloses a method for preparing a regorafenib intermediate; a compound represented by the formula II and a compound represented by the formula III are subjected to three stages of a step A, a step B and a step C, intermediates of all the stages are not separated, and thus the regorafenib intermediate I is prepared. According to the method, the intermediates of all the steps are not separated, post-treatment procedures are reduced, the process operational flow is saved, the solvent recovery and utilization efficiency is improved, pollution emissions and energy consumption are reduced, the requirements on green chemical process are met, and the method is suitable for industrialized production.
A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib
Du, Fangyu,Zhou, Qifan,Shi, Yajie,Yu, Miao,Sun, Wenjiao,Chen, Guoliang
, p. 576 - 586 (2019/02/01)
A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.
2-OXO-THIAZOLE DERIVATIVES AS A2A INHIBITORS AND COMPOUNDS FOR USE IN THE TREATMENT OF CANCERS
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Page/Page column 106-107, (2018/10/25)
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof. The invention further relates to the use of the compounds of Formula (I) as A2A inhibitors. The invention also relates to the use of the compounds of Formula (I) for the treatment and/or prevention of cancer. The invention also relates to a process for manufacturing compounds of Formula (I).
A 4 - amino -3 - fluoro phenol high efficient synthesis method (by machine translation)
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Paragraph 0023-0064, (2019/01/05)
The invention discloses a 4 - amino - 3 - fluoro phenol high efficient synthesis method, specifically comprises the following steps: first preparing porous polystyrene micro-ball, and then added to the hydrolysate of titanium tetrachloride, the reaction is carried out under certain conditions to make the supported catalyst, finally a pair of nitro phenol as raw materials to make the 3 - fluoro - - 4 nitro phenol, then in the above prepared under the catalysis of the supported catalyst, dropping the sodium borohydride solution reaction, to obtain the target product. The method is simple in operation, the equipment requirement is low, the yield is high. (by machine translation)
AN IMPROVED PROCESS FOR THE PREPARATION OF REGORAFENIB
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Page/Page column 6; 7, (2017/09/02)
The present invention relates to an improved process for the preparation of Regorafenib with genotoxic impurities at well below threshold limit and high yield. The present invention also relates to an improved process for the preparation of regorafenib form-I with high purity.
4-amino-3-fluorophenol and synthesizing method thereof
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, (2016/10/10)
The invention discloses 4-amino-3-fluorophenol and a synthesizing method thereof.The synthesizing method comprises the steps that fluoroaniline serves as a raw material, a diazo-reaction is carried out first, then a fluorine resolving reaction is carried out, and a white diazonium salt solid is obtained; then, the white diazonium salt solid is subjected to a hydrolysis reaction, and 3-fluorophenol is obtained; 3-fluorophenol is then subjected to a nitration reaction, and 3-fluorine-4-nitrophenol is obtained; then, obtained 3-fluorine-4-nitrophenol is reduced, and 4-amino-3-fluorophenol is obtained.According to 4-amino-3-fluorophenol and the synthesizing method thereof, ionic liquid serves as a reaction solvent, the volatility is low, environment is easily protected, and no harm is caused to the human body; in the reaction of reducing nitro groups into amino groups, the microwave heating mode is adopted, so that the reaction efficiency is greatly improved, and the product yield is increased.
TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE
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Paragraph 0607; 0608, (2016/12/22)
Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
