Design, synthesis and antidiabetic activity studies of purine derivatives
10.16438/j.0513-4870.2022-1187
- VernacularTitle:嘌呤衍生物的设计、合成及其降糖活性研究
- Author:
Su-mei SHI
;
Hui-lan LI
;
Wen-qin LIU
;
Xi-de YE
;
Shao-kun ZHANG
;
Jia-hui LI
;
Yuan-ying FANG
;
Zun-hua YANG
- Publication Type:Research Article
- Keywords:
GPR119;
DPP-4;
esign;
synthesis;
antidiabetic activity
- From:
Acta Pharmaceutica Sinica
2023;58(5):1275-1282
- CountryChina
- Language:Chinese
-
Abstract:
Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.
