20950-96-3Relevant academic research and scientific papers
Discovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I
Chen, Caiping,Cheng, Keguang,Cheng, Yalong,Dai, Liang,Li, Haobin,Qian, Ming,Sun, Geng,Wang, Pengfei,Wen, Xiaoan,Xu, Qing-Long,You, Yanping,Yuan, Haoliang,Zhou, Xinyu
supporting information, (2020/06/08)
Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogues that activate AMPK without inhibition of complex I, 27 analogues of AdipoRon were designed, synthesized and biologically evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.
Design, synthesis, and biological evaluation of sorafenib derivatives containing indole (ketone) semicarbazide analogs as antitumor agents
Li, Wen,Qi, Ya-Yun,Wang, Yuan-Yuan,Gan, Yi-Yuan,Shao, Li-Hui,Zhang, Li-Qiong,Tang, Zhen-Hua,Zhu, Mei,Tang, Si-Yu,Wang, Zhen-Chao,Ouyang, Gui-Ping
, p. 2548 - 2560 (2020/04/02)
A series of new sorafenib derivatives was designed and synthesized. The antiproliferative activity of the synthesized compounds against human lung cancer cell (A549), human pancreatic cancer cell (PC-3), human leukemia cell (K562), and human hepatoma cell (SMMC-7721) was evaluated by MTT assay. The results revealed that several compounds displayed more significant antitumor activities than commercial anticancer agent sorafenib against SMMC-7721. In addition, compounds 7a, 7g, 7l, 7m, and 7p represented obvious growth inhibition with IC50 values of 1-9 μM against four cancer cell lines, demonstrating more predominant activities against cancer cells as compared to sorafenib. Furthermore, some structure-activity relationships have also been established. Compounds containing indole and benzene ring substituted by halogen showed better activity than sorafenib. Wound healing assay suggested that cells would be targeted on their migratory capacity by 7g, potentially affecting the migration activity of these tumors. The effects of A549 and PC-3 cell apoptosis induced by compound 7g were significantly increased compared with sorafenib. Importantly, the result of western blot assay showed that 7g inhibited cell growth by suppressing the activity of EGFR, especially the expression of p-EGFR (Tyr1068).
Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones
Du, Guohua,Jia, Xinxin,Li, Yan,Liu, Qi,Wang, Shiyi,Zeng, Binglin,Zhang, Chen
, (2020/05/29)
Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anti
Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3
Li, Yingxiu,Ye, Tianyu,Xu, Le,Dong, Yuhong,Luo, Yong,Wang, Chu,Han, Yufei,Chen, Ke,Qin, Mingze,Liu, Yajing,Zhao, Yanfang
, (2019/08/12)
Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” phenyl ring and “B” phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.
2 - Amino pyrimidine compounds and their use (by machine translation)
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Paragraph 0099; 0110; 0111, (2019/10/22)
The invention belongs to the technical field of pharmaceutical chemical synthesis, relates to the general formula (I) indicated by the 2 - amino pyrimidine compounds and their pharmaceutically acceptable salt, solvate or prodrug, their method of preparation and containing pharmaceutical composition of said compound, wherein substituent R1 , R2 , R6 With the meanings given in the specification. The invention also relates to the compounds of the formula I or its pharmaceutical composition for treating and/or preventing malignant blood diseases or other proliferative diseases in the use of the medicament. (by machine translation)
Spontaneous and direct transformation of N,O-diaryl carbamates into N,N′-diarylureas
Yamasaki, Ryu,Honjo, Yutaka,Ito, Ai,Fukuda, Kazuo,Okamoto, Iwao
, p. 880 - 884 (2018/09/10)
We have discovered a spontaneous reaction of N,O-diaryl carbamates to afford symmetrical N,N′-diarylureas. Optimization of the conditions indicated that N,N-dimethylformamide (DMF) was the best solvent and triethylamine (Et3N) was the best additive for this transformation. The reaction requires the presence of aryl groups on the nitrogen and oxygen atoms of carbamates. Substrates bearing an electron-donating methoxy group on either of the aryl groups reacted slowly under these conditions.
Highly Regioselective Carbamoylation of Electron-Deficient Nitrogen Heteroarenes with Hydrazinecarboxamides
He, Zeng-Yang,Huang, Chao-Fan,Tian, Shi-Kai
supporting information, p. 4850 - 4853 (2017/09/23)
The use of hydrazinecarboxamides as a new class of carbamoylating agents has been established through the dehydrazinative Minisci reaction of electron-deficient nitrogen heteroarenes. A wide range of electron-deficient nitrogen heteroarenes, including isoquinoline, quinoline, pyridine, phenanthridine, quinoxaline, and phthalazine, underwent copper/acid-catalyzed oxidative carbamoylation with hydrazinecarboxamide hydrochlorides to afford structurally diverse nitrogen-heteroaryl carboxamides as single regioisomers in moderate to excellent yields. The functional group tolerance was substantially demonstrated in the direct carbamoylation of quinine obviating multistep sequences involving protecting groups and prefunctionalization of the heterocycle.
N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compound as well as preparation method and application thereof
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Paragraph 0072; 0073; 0088; 0089, (2017/12/28)
The invention belongs to the technical field of medicinal chemistry, in particular to N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compounds as well as preparation methods and application thereof. The compounds have the structure shown in the formula I. The compounds are proved that the compounds can improve the image recognition memory, the working and learning memory, the spatial learning and memory ability of model rats and has good anti-alzheimer effects by the new object discrimination experiments, Y-maze experiments, positioning navigation and space exploration experiments in mats. The formula I is shown in the description.
Silver-mediated radical coupling reaction of isocyanides and alcohols/phenols in the presence of water: unprecedented hydration and radical coupling reaction sequence
Zhang, Lin,Xiao, Pin,Guan, Xiaoxue,Huang, Zhouliang,Zhang, Jingping,Bi, Xihe
supporting information, p. 1580 - 1583 (2017/02/23)
The radical coupling of isocyanides and alcohols/phenols promoted by silver in the presence of water is reported for the first time, which led to the formation of diverse carbamates. In contrast to the well-known 1,1-addition to form imidoyl radicals, a novel reaction mechanism, involving sequential hydration of isocyanides and coupling with alkoxyl/phenoxyl radicals, is disclosed by combining experimental and theoretical studies.
Preparation of substituted semicarbazides from corresponding amines and hydrazines via phenyl carbamates
Hron, Rebecca,Jursic, Branko S.
supporting information, p. 1540 - 1543 (2014/03/21)
A simple synthetic procedure for the conversion of amines and hydrazines into substituted semicarbazides was developed. The initial condensation between the desired amine and phenyl chloroformate into phenyl carbamate is followed by the addition of hydrazine under basic conditions. The reaction is tolerable to a variety of functional groups, with mild conditions and high percent yields.
