52304-61-7Relevant academic research and scientific papers
PRODRUGS BASED ON GEMCITABINE STRUCTURE AS WELL AS SYNTHETIC METHOD AND APPLICATION THEREOF
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Page/Page column 9, (2012/03/26)
Prodrugs based on gemcitabine structure shown in formula (I) as well as their synthetic method and application are disclosed in the present invention, wherein the definitions for the groups of a, b, c, d, E, Z and V are described in the specification. By modifying the N4 group, the solubility, the bioavailability and the organ specificity of the prodrugs are improved. Therefore, the fast metabolism problem is overcome for the produced prodrugs compounds. Intestinal toxicity induced by gemcitabine is decreased. Thereby, the prodrugs can be delivered by oral administration in clinics and further improve their anti-tumor, anti-cancer, anti-infection and diffusion preventing capability, and can also specifically act on liver or colon. The synthetic method is simple and adapted to industrial production.
Prodrugs Based on Gemcitabine Structure and Synthetic Methods and Applications Thereof
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Page/Page column 5, (2012/04/18)
Prodrugs based on gemcitabine structure shown in formula (I) as well as their synthetic method and application are disclosed in the present invention, wherein the definitions for the groups of a, b, c, d, E, Z and V are described in the specification. By modifying the N4 group, the solubility, the bioavailability and the organ specificity of the prodrugs are improved. Therefore, the fast metabolism problem is overcome for the produced prodrugs compounds. Intestinal toxicity induced by gemcitabine is decreased. Thereby, the prodrugs can be delivered by oral administration in clinics and further improve their anti-tumor, anti-cancer, anti-infection and diffusion preventing capability, and can also specifically act on liver or colon. The synthetic method is simple and adapted to industrial production.
Acetic anhydride mediated condensation of aromatic o-diacid dichlorides with benzimidazoles to provide electro-reducible p-dione adducts
Joyce, Eamonn,Kavanagh, Paul,Leech, Dónal,Karpinska, Jolanta,McArdle, Patrick,Aldabbagh, Fawaz
experimental part, p. 3788 - 3791 (2012/09/10)
Acetic anhydride mediates a facile and rapid condensation of benzimidazole with aromatic o-diacid dichlorides to precipitate p-dione adducts in excellent yields. Condensation with pyridine-3,4-dicarbonyl dichloride produced a 1:1 mixture of isomeric p-diones. The X-ray crystal structure of one of the latter isomers revealed unusual high density, and inter-layer separation similar to graphite. Cyclic voltammetry demonstrated that p-dione is capable of two consecutive one-electron-reductions with formal potentials influenced by the fused (hetero)aromatic and substituent effects.
Synthesis and Biological Evaluation of Oral Prodrugs Based on the Structure of Gemcitabine
Zhao, Cuirong,Xue, Xiaoxia,Li, Gang,Sun, Cuicui,Sun, Changjun,Qu, Xianjun,Li, Wenbao
experimental part, p. 479 - 488 (2012/10/07)
A series of oral prodrugs based on the structure of gemcitabine (2′,2′-difluorodeoxycytidine) were synthesised by introducing an amide group at the N4-position of the cytidine ring. A total of 16 compounds were obtained, and their chemical and biological characteristics were evaluated. The half-maximal inhibitory concentrations (IC50s) for most of these compounds were higher than that of gemcitabine in vitro. Compounds 5d and 5m, the representative compounds, were examined in terms of their physiological stabilities and pharmacokinetics. Compound 5d showed good stability in PBS and simulated intestinal fluid, and an analysis of its pharmacokinetics in mice suggested that the introduction of an amide group to gemcitabine could greatly improve its bioavailability. Further evaluation of compound 5din vivo showed that this compound possesses higher activity than gemcitabine against the growth of HepG2 human hepatocellular carcinoma cells and HCT-116 colon adenocarcinoma cells with less toxicity to animals. These results suggest that compound 5d could be further developed as a potential oral anticancer agent for clinical applications in which gemcitabine is currently used. A series of oral prodrugs based on the structure of gemcitabine were synthesized. Physiological and metabolic stabilities, pharmacokinetics and antitumor activities were evaluated for representative compounds.
Grignard Reactions on Ortho Dicarboxylic Arene Derivatives. Synthesis of 1,3-Dithienylisothianaphthene Compounds
Kiebooms, Rafa?l H. L.,Adriaensens, Peter J. A.,Vanderzande, Dirk J. M.,Gelan, Jan M. J. V.
, p. 1473 - 1480 (2007/10/03)
1,3-Dithienylisothianaphthene (10a) is obtained through ring closure of 1,2-dithienoylbenzene (7a). The synthesis of 7a has been accomplished based on a Grignard reaction by adding 2-thiophene-magnesium bromide to 1,2-di(S-(2-pyridinyl)) benzenedithioate (6b) to obtain 7a in a yield of 95%. The use of 6b avoids the formation of the corresponding 3,3-dithienyl-3H-isobenzofuran-1(3H)-one (dithienylphthalide, 8). The same procedure is applied to obtain 1,3-dithienyl-4,5,6,7-tetradeuterioisothianaphthene (10b) and 1,3-dithienyl-4,5,6,7-tetrafluoroisothianaphthene (10c). The synthesis of the 2,3-dithienoylpyridine (12a), 3,4-dithienoylpyridine (12b), and 2,3-dithienoylpyrazine (12c) however fails. The presence of nitrogen in the central ring system influences the result of the Grignard reaction. Possibly the free electron pair of the nitrogen interferes with the formation of a stable six-membered ring intermediate which is essential for the diketone formation.
