Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids

GAO Yang; YIN Wei; LIU Jingchao; KANG Fenghua; JIAN Yanlin; ZHOU Jinpei; HUANG Zhangjian; ZHANG Yihua

doi:10.11665/j.issn.1000-5048.20170104

Journal of China Pharmaceutical University > 2017 > 48(1): 23-30. > DOI: 10.11665/j.issn.1000-5048.20170104

GAO Yang, YIN Wei, LIU Jingchao, KANG Fenghua, JIAN Yanlin, ZHOU Jinpei, HUANG Zhangjian, ZHANG Yihua. Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids[J]. Journal of China Pharmaceutical University, 2017, 48(1): 23-30. DOI: 10.11665/j.issn.1000-5048.20170104

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Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids

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In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine(TMP)/chalcone hybrids( 2 - 26 )were synthesized and evaluated based on the principle of bioisostere and hybridization. They exerted inhibitory activity against adenosine diphosphate(ADP)-induced and arachidonic acid(AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC₅₀ of 0. 14 mmol/L on ADP-induced platelet aggregation(9. 1 folds of TMP and 10. 5 folds of chalcone)and 0. 09 mmol/L on AA-induced platelet aggregation(8. 8 folds of TMP and 10. 0 folds of chalcone), which was superior to clinically used anti-platelet drug aspirin(ASP, IC₅₀=0. 15 mmol/L).
- tetramethylpyrazine,
- chalcone,
- hybridization,
- aspirin,
- antiplatelet,
- synthesis

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[1]	Ohira T,Shahar E,Chambless LE,et al.Risk factors for ischemic stroke subtypes the atherosclerosis risk in communities study[J].Stroke,2006,37(10):2493-2498.
[2]	Uchiyama S,Demaerschalk BM,Goto S,et al.Stroke prevention by cilostazol in patients with atherothrombosis:meta-analysis of placebo-controlled randomized trials[J].J Stroke Cerebrovasc Dis,2009,18(6):482-490.
[3]	Yang CY,Huang ZJ,Ling JJ,et al.Synthesis and evaluation of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids as novel platelet aggregation inhibitors[J].J China Pharm Univ(中国药科大学学报),2013,44(3):202-206.
[4]	Ren Y,Liu EH,Lan L,et al. Protective effects and possible mechanism of Xingxiong sodium chloride injection on cerebral ischemia-reperfusion injury in rats[J].J China Pharm Univ (中国药科大学学报),2015,46(6):719-723.
[5]	Deng L, Guo X, Zhai L, et al. Ligustrazine derivatives. part 4:design,synthesis,and biological evaluation of novel ligustrazine-based stilbene derivatives as potential cardiovascular agents[J].Chem Biol Drug Des,2012,79(5):731-739.
[6]	Li G, Xu X, Xu K, et al. Ligustrazinyl amides: a novel class of ligustrazine-phenolic acid derivatives with neuroprotective effects[J].Chem Cent J,2015,9(1):1-9.
[7]	Benzhong M.Analysis of clinical efficacy of ligustrazine and xuesaitong on the treatment of ischemic stroke[J].Med Innov Chin(中国医学创新),2013,10(9):32-33.
[8]	Hu WY,Chen J,Jiang ZY,et al.Synthesis and biological activity of chalcone derivatives as potent activators of Nrf2[J].J China Pharm Univ (中国药科大学学报),2016,47(6):666-672.
[9]	Wu CM,Lin KW,Teng CH,et al.Chalcone derivatives inhibit human platelet aggregation and inhibit growth in human bladder cancer cells[J].Biol Pharm Bull,2014,37(7):1191-1198.
[10]	Sahu NK,Balbhadra SS,Choudhary J,et al.Exploring pharmacological significance of chalcone scaffold:a review[J].Curr Med Chem,2012,19(2):209-225.
[11]	Schumann H,Luo HK.2,5-Dimethyl-3,6-bis[(2,6-diisopropylphenylimino)methyl]-and 2,6-Bis[(2,6-diisopropylphenylimino)methyl]pyrazine:two new chelating ligands for transition metal complexes[J].Z Naturforsch B,2014,60(1):22-24.
[12]	Born GVR,Cross MJ.The aggregation of blood platelets[J].J Physiol,1963,168(1):178-195.

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