Design, synthesis, and structure-activity relationship of carbamate-tethered aryl propanoic acids as novel PPARα/γ dual agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 13, 2007, Pages 3595-3598

  Kim, Nam Jung ^a   Lee, Kwang Ok ^a   Koo, Bon Woong ^a   Li, Funan ^a   Yoo, Ja Kyung ^b   Park, Hyun Ju ^b   Min, Kyung Hoon ^b   Lim, Joong In ^c   Kim, Mi Kyung ^c   Kim, Jin Kwan ^c   Suh, Young Ger ^a  

^a Seoul National University   (South Korea)

^b Sungkyunkwan University   (South Korea)

^c Dong A Pharmaceutical Company   (South Korea)

Author keywords

PPAR dual agonists; PPARs; Type 2 diabetes

Indexed keywords

GEMFIBROZIL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PROPIONIC ACID DERIVATIVE; ROSIGLITAZONE;

AGONIST; ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

CARBAMATES; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; GLYCINE; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OXAZOLES; PPAR ALPHA; PPAR GAMMA; PROPIONIC ACIDS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLIDINEDIONES; TRANS-ACTIVATION (GENETICS);

EID: 34250199774     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.04.057     Document Type: Article

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13. The X-ray structures of PPARα and PPARγ complexed with the ligand were taken from the RCSB Protein Data Bank (PDB code: 1K7L for PPARα/1K74 for PPARγ). The protein was prepared for docking, using the protein preparation and refinement utility provided by Surflex-Dock™ suite in SYBYL 7.0. Water molecules of the crystal structure were removed from the complexes, and the hydrogen atoms were added computationally at appropriate positions. Calculations for the docking studies between the prepared PPARα protein and the selected compounds were performed using SYBYL 7.0 software.