摘要
为寻找新型的PPAR激动剂, 本研究以L-酪氨酸为起始原料, 经过羧基酯化、氨基酰胺化、酚羟基溴烷基化及溴烷基胺基化等多步反应, 成功合成了20个含苯氧乙酰基结构单元的L-酪氨酸衍生物TM1 （总收率21%～75%）; TM1碱性水解, 得到16个相应的水解产物TM2 （77%～99%）。共得到4个中间体和36个目标化合物, 其中39个新化合物的结构得到1H NMR、13C NMR证实, 35个新化合物进一步通过HR-MS确证。体外抗糖尿病活性结果表明, 目标化合物的PPAR相对激动活性整体较弱, 最高者TM2i为50.01%, 需要进一步改进。
The design, synthesis and bioevaluation of a series of novel L-tyrosine derivatives as peroxisome proliferator-activated receptor （PPAR） agonists are reported. Four intermediates and twenty L-tyrosine derivatives containing phenoxyacetyl moiety TM1 were synthesized starting from L-tyrosine via four step reactions including the esterification of carboxyl group, phenoxyacetylation of α-amino group, bromoalkylation of phenolic hydroxyl group and then nucleophilic substitution reaction with various heterocyclic amines in 21%-75% overall yield. Subsequently TM1 were hydrolyzed to give sixteen corresponding target compounds TM2 in 77%-99% yield. The chemical structures of the thirty-nine new compounds were identified using 1H NMR, 13C NMR techniques and thirty-five were confirmed by HR-MS techniques. Screening results in vitro showed that the PPAR relative activation activities of the target molecules are weak overall, while compound TM2i reaches 50.01%, which hints that the molecular structures of these obtained compounds need to be modified further.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第10期1570-1578,共9页
Acta Pharmaceutica Sinica
基金
重庆市科技攻关计划资助项目(CSTC
2011AB5001
2011AC1053
2011AC5107)
