7073-36-1Relevant articles and documents
Synthesis and Antiproliferative Activities of Novel Substituted 5-Anilino-α-Glucofuranose Derivatives
Hou, Qiaoli,Li, Baolin,Li, Xiabing,Sun, Baoli,Wang, Lili,Wang, Wei,Zhang, Yaling
, (2020/05/05)
In order to find novel antitumor candidate agents with high efficiency and low toxicity, 14 novel substituted 5-anilino-α-glucofuranose derivatives have been designed, synthesized and evaluated for antiproliferative activities in vitro. Their structures were characterized by NMR (1H and 13C) and HR-MS, and configuration (R/S) at C(5) was identified by two-dimensional 1H,1H-NOESY-NMR spectrum. Their antiproliferative activities against human tumor cells were investigated by MTT assay. The results demonstrated that most of the synthesized compounds had antiproliferative effects comparable to the reference drugs gefitinib and lapatinib. In particular, (5R)-5-O-(3-chloro-4-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}anilino)-5-deoxy-1,2-O-(1-methylethylidene)-α-glucofuranose (9da) showed the most potent antiproliferative effects against SW480, A431 and A549 cells, with IC50 values of 8.57, 5.15 and 15.24 μm, respectively. This work suggested 5-anilino-α-glucofuranose as an antitumor core structure that may open a new way to develop more potent anti-cancer agents.
Design, synthesis and biological evaluation of novel 7H-benzo [c] [1, 3] dioxolo [4, 5-f] chromen-7-one derivatives with potential anti-tumor activity
Zhou, Shiyang,Huang, Gangliang
, (2020/10/29)
In this study, a series of novel 7H-benzo [c] [1,3] dioxolo [4, 5-f] chromen-7-one derivatives were obtained by structural modification of the lead compounds with Fissitungfine B. A total 15 compounds were designed, synthesized and evaluated as inhibitors of tumor. These target compounds have the novel chemical structures that named three six-membered rings including one lactone six-membered ring. In vitro assay, the results showed that the target compounds have a broad spectrum and strong of anti-tumor activity. Such as the target compound 4n to MCF-7 was IC50 = 0.35 ± 0.01 μM, to A-549 was IC50 = 0.37 ± 0.01 μM, to Hela was IC50 = 0.56 ± 0.02 μM, to MDC-803 was IC50 = 0.53 ± 0.02 μM and COLO-205 was IC50 = 0.50 ± 0.02 μM in vitro. At the same time, in vivo anti-tumor activity assay results showed that the target compounds had a good inhibitory effect on tumor growth. Among them, the target compound 4n had the best anti-tumor activity, it could inhibit tumor growth well at a low dose. The target compound 4n could be used as a candidate drug for further research and development, in order to be used as early as application in the clinical treatment of tumors.
Design and synthesis of arylamidine derivatives as serotonin/norepinephrine dual reuptake inhibitors
Wen, Hui,Qin, Wen,Yang, Guangzhong,Guo, Yanshen
, (2019/02/03)
To improve the in vivo antidepressant activity of previously reported serotonin (5-HT) and norepinephrine (NE) dual reuptake inhibitors, three series of arylamidine derivatives were designed and synthesized. The in vitro 5-HT and NE reuptake inhibitory activities of these compounds were evaluated, and compound II-5 was identified as the most potent 5-HT (IC50 = 620 nM) and NE (IC50 = 10 nM) dual reuptake inhibitor. Compound II-5 exhibited potent antidepressant activity in the rat tail suspension test and showed an acceptable safety profile in a preliminary acute toxicity test in mice. Our results show that these arylamidine derivatives exhibit potent 5-HT/NE dual reuptake inhibition and should be explored further as antidepressant drug candidates.
Heterocyclic Compounds and Methods of Use
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Paragraph 0431; 0471; 0475, (2018/03/01)
This disclosure provides compounds and methods of using those compounds to treat liver fibrosis, including liver fibrosis which is a precursor to, is concurrent with, is associated with, or is secondary to nonalcoholic steatohepatitis (NASH); elevated cholesterol levels, and insulin resistance.
Diarylamino glucosan derivative, and preparation method and anti-tumor purpose thereof
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Paragraph 0108; 0109; 0110; 0111; 0122; 0133, (2017/04/26)
The invention belongs to the field of medicinal chemistry, and particularly relates to a diarylamino glucosan derivative, and a preparation method and an anti-tumor purpose thereof, wherein the diarylamino glucosan derivative particularly relates to a compound shown as a formula I. The invention also relates to the preparation method of the diarylamino glucosan derivative, and the purpose of the diarylamino glucosan derivative in an aspect of preparing medicine for treating tumor diseases. The diarylamino glucosan derivative particularly has the obvious inhibition effects on human skin quamous cell carcinoma cells, human lung carcinoma cells and human colon cancer cells.
2-Halobenzoyl chlorides in the synthesis of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one derivatives
Shlenev,Tarasov,Filimonov,Agat’ev,Danilova,Suponitskii, K. Yu.
, p. 1870 - 1877 (2018/02/06)
New nitro and sulfonamide derivatives of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one have been synthesized by cyclocondensation of 1,3,4-thiadiazol-2-amines with 2-halobenzoyl chlorides containing electron-withdrawing substituents in positions 3, 4, and 5. An improved procedure has been proposed for the preparation of intermediate 2-fluoro-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamides containing a sulfamoyl group in the 5-position via selective acylation of 5-methyl-1,3,4-thiadiazol-2-amine with 5-chlorosulfonyl-2-fluorobenzoyl chloride, followed by sulfonylation of amines.
HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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Paragraph 0145; 0188, (2015/03/16)
This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists. Compounds of the invention may also find use in treating cancer. Presented herein are novel compounds bearing a perhaloalkylsulfonamide moiety. Such compounds, in addition to being highly effective SREBP inhibitors, are also unexpectedly highly bioavailable in vivo. Heteroaromatic compounds bearing sulfonamide groups are prone to several ionic states, based on the inherent pKa values.
HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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Paragraph 0407, (2015/03/16)
This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists.
Lowering the pKa of a bisimidazoline lead with halogen atoms results in improved activity and selectivity against Trypanosoma brucei in vitro
Ríos Martínez, Carlos H.,Nué Martínez, J. Jonathan,Ebiloma, Godwin U.,De Koning, Harry P.,Alkorta, Ibon,Dardonville, Christophe
, p. 806 - 817 (2015/08/06)
Diphenyl-based bis(2-iminoimidazolidines) are promising antiprotozoal agents that are curative in mouse models of stage 1 trypanosomiasis but devoid of activity in the late-stage disease, possibly due to poor brain penetration caused by their dicationic nature. We present here a strategy consisting in reducing the pKa of the basic 2-iminoimidazolidine groups though the introduction of chlorophenyl, fluorophenyl and pyridyl ring in the structure of the trypanocidal lead 4-(imidazolidin-2-ylideneamino)-N-(4-(imidazolidin-2-ylideneamino)phenyl)benzamide (1). The new compounds showed reduced pKa values (in the range 1-3 pKa units) for the imidazolidine group linked to the substituted phenyl ring. In vitro activities (EC50) against wild type and resistant strains of T. b. brucei (s427 and B48, respectively) were in the submicromolar range with four compounds being more active and selective than 1 (SI > 340). In particular, the two most potent compounds (3b and 5a) acted approximately 6-times faster than 1 to kill trypanosomes in vitro. No cross-resistance with the diamidine and melaminophenyl class of trypanocides was observed indicating that these compounds represent interesting leads for further in vivo studies.
Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
Caraballo, Rémi,Larsson, Mikael,Nilsson, Stefan K.,Ericsson, Madelene,Qian, Weixing,Tran, Nam Phuong Nguyen,Kindahl, Tomas,Svensson, Richard,Saar, Valeria,Artursson, Per,Olivecrona, Gunilla,Enquist, Per-Anders,Elofsson, Mikael
, p. 191 - 209 (2015/09/15)
The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun. 2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.
