A series of compounds possessing 2-（3-phenyl）ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against...A series of compounds possessing 2-（3-phenyl）ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and Hep G2 cell lines using Sorafenib as the positive control.Compounds 6i showed a good to moderate inhibition on VEGFR-2 and PI3Ka which was proved by further molecular docking study. This study suggests that compound 6i is a potential dual inhibitor of VEGFR-2 and PI3Ka and is applicable for further investigation.展开更多
A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines ...A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10 c showed promising inhibition of hedgehog（Hh） signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10 c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.展开更多
A series of sulfenimine cephalosporin sulfoxide derivatives （Ta-v） were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested c...A series of sulfenimine cephalosporin sulfoxide derivatives （Ta-v） were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalospor- inase compared with the tazobactam. The most promising compounds 7c and 7n （IC50 ~ 7.6 and 8.6 μmol/L, respectively） were further investigated in combination with cefradine against a variety of clinical isolated fi-lactamase-producing bacterial strains.展开更多
A facile and efficient protocol was developed to access 2-alkoxy-4-amino-N-arylthiazole-5-carbox- amides through a three-component one-pot reaction, which involved potassium methyl cyanimido- dithiocarbonate, 2-halo-N...A facile and efficient protocol was developed to access 2-alkoxy-4-amino-N-arylthiazole-5-carbox- amides through a three-component one-pot reaction, which involved potassium methyl cyanimido- dithiocarbonate, 2-halo-N-arylacetamides and alcohols. The easy availability and the broad structural diversity of substrates make the reaction useful for the construction of libraries in drug discovery.展开更多
A series of pyrrolo[1,2-a]pyrazinone compounds （Sa-gf） were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTF method. Some of the compounds showed potentia...A series of pyrrolo[1,2-a]pyrazinone compounds （Sa-gf） were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTF method. Some of the compounds showed potential antitumor activity against three tumor cell lines. Among them, compounds 9c and 9d showed the most potent cytotoxic activity. The preliminary mechanism of action was discussed.展开更多
A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-ca...A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARg.When given orally to normal mice,the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.展开更多
基金the financial supports from the NSFC (No. 21272134)Shenzhen Municipal government SZSITIC (Nos. JCYJ20130402145002384, ZDSY20120619141412872)
文摘A series of compounds possessing 2-（3-phenyl）ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and Hep G2 cell lines using Sorafenib as the positive control.Compounds 6i showed a good to moderate inhibition on VEGFR-2 and PI3Ka which was proved by further molecular docking study. This study suggests that compound 6i is a potential dual inhibitor of VEGFR-2 and PI3Ka and is applicable for further investigation.
基金supported by Program for Innovative Research Team of the Ministry of Education of ChinaProgram for Liaoning Innovative Research Team in Universitythe Innovation and entrepreneurship training program for college students in Liaoning Province (No. 201410163009)
文摘A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10 c showed promising inhibition of hedgehog（Hh） signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10 c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.
文摘A series of sulfenimine cephalosporin sulfoxide derivatives （Ta-v） were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalospor- inase compared with the tazobactam. The most promising compounds 7c and 7n （IC50 ~ 7.6 and 8.6 μmol/L, respectively） were further investigated in combination with cefradine against a variety of clinical isolated fi-lactamase-producing bacterial strains.
基金supported by the National Natural Science Foundation of China(No.81273380)‘‘863’’ Program of China(No.2012AA020302)
文摘A facile and efficient protocol was developed to access 2-alkoxy-4-amino-N-arylthiazole-5-carbox- amides through a three-component one-pot reaction, which involved potassium methyl cyanimido- dithiocarbonate, 2-halo-N-arylacetamides and alcohols. The easy availability and the broad structural diversity of substrates make the reaction useful for the construction of libraries in drug discovery.
文摘A series of pyrrolo[1,2-a]pyrazinone compounds （Sa-gf） were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTF method. Some of the compounds showed potential antitumor activity against three tumor cell lines. Among them, compounds 9c and 9d showed the most potent cytotoxic activity. The preliminary mechanism of action was discussed.
基金supported by grants from the National S&T Major Special Project on Major New Drug Innovation(No.2009zx09103-036)the National Nature Science Foundation of China(No.30572256).
文摘A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase(GK)activators.Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARg.When given orally to normal mice,the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.
