Design, synthesis and evaluation of phenoxyacetic acid-based PTP1B inhibitors
10.16438/j.0513-4870.2023-1195
- VernacularTitle:苯氧乙酸类PTP1B抑制剂的设计、合成及活性研究
- Author:
Jin-ying TIAN
;
Jun-zheng LIU
;
Shu-en ZHANG
;
Xiao-lin ZHANG
;
Fei YE
;
Zhi-yan XIAO
- Publication Type:Research Article
- Keywords:
PTP1B inhibitor;
pTyr mimetic;
phenoxyacetic acid;
insulin sensitizer
- From:
Acta Pharmaceutica Sinica
2023;58(12):3684-3690
- CountryChina
- Language:Chinese
-
Abstract:
Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.
