Design, synthesis and PPAR agonist activities of novel L-tyrosine derivatives containing phenoxyacetyl moiety.
- Author:
Li-Jiang ZHOU
1
;
Ju-Fang YAN
2
;
Kun ZHANG
1
;
Li FAN
1
;
Xin CHEN
2
;
Da-Cheng YANG
1
Author Information
1. School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
2. Drug Screening Center Chengdu DiAo Pharmaceutical Group Co. Ltd, Chengdu 610041, China.
- Publication Type:Journal Article
- MeSH:
Hep G2 Cells;
Humans;
Hypoglycemic Agents;
chemical synthesis;
chemistry;
pharmacology;
Molecular Structure;
Peroxisome Proliferator-Activated Receptors;
agonists;
metabolism;
Phenoxyacetates;
chemical synthesis;
chemistry;
pharmacology;
Structure-Activity Relationship;
Tyrosine;
analogs & derivatives;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2013;48(10):1570-1578
- CountryChina
- Language:Chinese
-
Abstract:
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 a-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.