Synthesis of the novel liqustrazine derivatives and Their protective effect on injured vascular endothelial cell damaged by hydrogen peroxide.
A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was designed and synthesized. Most compounds were found to be 1.5-4.5-fold higher potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal vascular endothelial cells and in protecting against hyperoxic acute injury. The most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation rate (P(max)) of 88.57% at the concentration of 0.1 mmol L(-1). Structure-activity relationships of these compounds were discussed.
Liu
Xinyong
X
Institute of Medicinal Chemistry, School of Pharmacy, No. 44 Wenhuaxi Road, 250012, Jinan, China. xinyongl@jn-lublic.sd.cninfo.net
Zhang
Rui
R
Xu
Wenfang
W
Li
Chaowu
C
Zhao
Quanqin
Q
Wang
Xingpo
X
D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D030004:Ligusticum / Q000737:chemistry; D011719:Pyrazines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014470:Umbilical Cord / Q000166:cytology / Q000187:drug effects
D000975:Antioxidants; D011719:Pyrazines; D006861:Hydrogen Peroxide; C017953:tetramethylpyrazine