Design, synthesis and PPAR agonist activities of novel L-tyrosine derivatives containing phenoxyacetyl moiety / 药学学报
Acta Pharmaceutica Sinica
; (12): 1570-1578, 2013.
Article
in Zh
| WPRIM
| ID: wpr-298042
Responsible library:
WPRO
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.
Full text:
1
Database:
WPRIM
Main subject:
Pharmacology
/
Phenoxyacetates
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Structure-Activity Relationship
/
Tyrosine
/
Molecular Structure
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Chemistry
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Peroxisome Proliferator-Activated Receptors
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Hep G2 Cells
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Hypoglycemic Agents
/
Metabolism
Limits:
Humans
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2013
Document type:
Article