19313-87-2Relevant articles and documents
Unravelling the anticancer potency of 1,2,4-triazole-N-arylamide hybrids through inhibition of STAT3: synthesis and in silico mechanistic studies
Turky, Abdallah,Bayoumi, Ashraf H.,Sherbiny, Farag F.,El-Adl, Khaled,Abulkhair, Hamada S.
, p. 403 - 420 (2020/08/25)
Abstract: The discovery of potent STAT3 inhibitors has gained noteworthy impetus in the last decade. In line with this trend, considering the proven biological importance of 1,2,4-triazoles, herein, we are reporting the design, synthesis, pharmacokinetic profiles, and in vitro anticancer activity of novel C3-linked 1,2,4-triazole-N-arylamide hybrids and their in silico proposed mechanism of action via inhibition of STAT3. The 1,2,4-triazole scaffold was selected as a privilege ring system that is embedded in core structures of a variety of anticancer drugs which are either in clinical use or still under clinical trials. The designed 1,2,4-triazole derivatives were synthesized by linking the triazole-thione moiety through amide hydrophilic linkers with diverse lipophilic fragments. In silico study to predict cytotoxicity of the new hybrids against different kinds of human cancer cell lines as well as the non-tumor cells was conducted. The multidrug-resistant human breast adenocarcinoma cells (MDA-MB-231) was found most susceptible to the cytotoxic effect of synthesized compounds and hence were selected to evaluate the in vitro anticancer activity. Four of the designed derivatives showed promising cytotoxicity effects against selected cancer cells, among which compound 12 showed the highest potency (IC50 = 3.61?μM), followed by 21 which displayed IC50 value of 3.93?μM. Also, compounds 14 and 23 revealed equipotent activity with the reference cytotoxic agent doxorubicin. To reinforce these observations, the obtained data of in vitro cytotoxicity have been validated in terms of ligand–protein interaction and new compounds were analyzed for ADMET properties to evaluate their potential to build up as good drug candidates. This study led us to identify two novel C3-linked 1,2,4-triazole-N-arylamide hybrids of interesting antiproliferative potentials as probable lead inhibitors of STAT3 with promising pharmacokinetic profiles. Graphic abstract: [Figure not available: see fulltext.]
Synthesis method of 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone
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Paragraph 0032, (2018/09/08)
The invention provides a synthesis method of 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone. The synthesis method comprises the following steps: 1) taking p-alkoxyaniline as a raw material to react with 3-chloro-propionyl chloride, so as to prepare N-(4-alkoxyphenyl)-3-chloropropene amide; 2) dissolving the N-(4-alkoxyphenyl)-3-chloropropene amide obtained by step 2) into an organic solvent and adding acatalyst palladium chloride; raising the temperature to 100 to 110 DEG C under the pressure of 3 to 5kg, and carrying out heat preservation and reaction for 3 to 4h; after cooling to room temperature, filtering; spinning and drying filtrate to remove the organic solvent, so as to obtain a 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone crude product; 3) recrystallizing the 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone crude product obtained by step 3), de-coloring and filtering to obtain an off-white color solid 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone. The synthesis method has the advantages of simplicity in operation, high yield and lower cost.
Preparation method of cilostazol
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Paragraph 0039-0040; 0043-0044; 0046-0047; 0049-0050; 0052, (2018/01/03)
The invention discloses a preparation method of cilostazol and belongs to the field of medicines. The preparation method comprises the following steps: firstly, reacting 4-methoxyaniline with 3-chloropropionyl chloride in the presence of a solvent or no solvent; after a TLC (thin layer chromatography) detecting reaction is finished, adding aluminum trichloride into a system, and carrying out temperature raising reaction for 1 to 16 hours to obtain 6-hydroxy-3,4-dihydroquinoline-2-keto; secondly, in the presence of alkali, carrying out heating reaction on the 6-hydroxy-3,4-dihydroquinoline-2-keto obtained in the first step and 5-(4-chlorobutyl)-1-cyclohexanyl tetrazole in normal propyl alcohol to obtain the cilostazol. The high-purity cilostazol can be obtained by adopting the method disclosed by the invention; the preparation method has the advantages of few steps of the whole synthetic route, high yield, low cost, less wastewater and suitability for industrial production.
