Design, synthesis, and evaluation of 2-alkoxydihydrocinnamates as PPAR agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 4, 2006, Pages 915-919

  Lu, Ying ^a   Guo, Zongru ^a   Guo, Yanshen ^a   Feng, Jun ^a   Chu, Fengming ^a  

^a INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

2 Alkoxydihydrocinnamates; Antidiabetes; PPAR agonists

Indexed keywords

2 ALKOXYDIHYDROCINNAMATE; CINNAMIC ACID DERIVATIVE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; ROSIGLITAZONE; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIVER; NON INSULIN DEPENDENT DIABETES MELLITUS;

CELL LINE; CINNAMATES; DRUG DESIGN; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PPAR ALPHA; PPAR GAMMA; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 30344436369     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.10.104     Document Type: Article

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11. General procedure: t-BuOK in i-butanol (1 mol/l) 5 ml was slowly dropped to a solution of 4-[2-(biphenyl-4-yloxy)-ethoxy]-benzaldehyde (5 mmol) and methoxy-acetic acid ethyl ester (5 mmol) in 20 ml dried DMF at 0°C. The reaction mixture was allowed to reach room temperature. While the reaction was completed, the mixture was poured into water, acidified with hydrochloric acid, and extracted with ethyl ester and the organic phase was dried with sodium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica gel using EA/PE (1/6) as eluents to give 0.505 g (yield 24.2%) of 2a. Sodium hydroxide hydrate (1 mol/l) 5 ml was added to a solution of 2a (224 mg) in 30 ml ethanol, then the reaction mixture was refluxed for 3 h, evaporated and acidified with diluted hydrochloric acid to pH = 1, and filtered. The crude product was crystallized to give 135 mg (yield 64.6%) of 1a as white crystals.