title: [Design, synthesis and PPAR agonist activities of novel L-tyrosine derivatives containing phenoxyacetyl moiety].
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.
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Li-Jiang
authors.initials: LJ
authors.lastname: Zhou
authors.affiliation: Drug Screening Center Chengdu DiAo Pharmaceutical Group Co. Ltd, Chengdu 610041, China.
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Yan
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.affiliation: Drug Screening Center Chengdu DiAo Pharmaceutical Group Co. Ltd, Chengdu 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Da-Cheng
authors.initials: DC
authors.lastname: Yang
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D010642:Phenoxyacetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D010642:Phenoxyacetates; D014443:Tyrosine