Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR α/γ agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 5, 2009, Pages 1451-1456

  Zhang, Hao ^a   Ryono, Denis E ^a   Devasthale, Pratik ^a   Wang, Wei ^a   O'Malley, Kevin ^a   Farrelly, Dennis ^a   Gu, Liqun ^a   Harrity, Thomas ^a   Cap, Michael ^a   Chu, Cuixia ^a   Locke, Kenneth ^a   Zhang, Litao ^a   Lippy, Jonathan ^a   Kunselman, Lori ^a   Morgan, Nathan ^a   Flynn, Neil ^a   Moore, Lisa ^a   Hosagrahara, Vinayak ^a   Zhang, Lisa ^a   Kadiyala, Pathanjali ^a   Xu, Carrie ^a   Doweyko, Arthur M ^a   Bell, Aneka ^a   Chang, Chiehying ^a   Muckelbauer, Jodi ^a   Zahler, Robert ^a   Hariharan, Narayanan ^a   Cheng, Peter T W ^a   more..

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Azole; Conformational constraint; Dual PPAR agonists; Pyrazole; Pyrrole; Triazole

Indexed keywords

1 PHENYL 1H 1,2,3 TRIAZOLE 5 CARBOXYLIC ACID; 1,2,3 TRIAZOLE DERIVATIVE; 1,3 ALKOXYBENZYL 1 PHENYL 3 CARBOXYPYRAZOLE; 5 (3 OXYBENZYL)PYRAZOLE 4 CARBOXYLIC ACID; 5 (4 OXYBENZYL)PYRAZOLE 4 CARBOXYLIC ACID; 5 OXYBENZYL 2 PHENYL 2H 1,2,3 TRIAZOLE 4 CARBOXYLIC ACID; GLUCOSE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PYRROLE DERIVATIVE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIABETES CONTROL; DIABETES MELLITUS; DRUG DESIGN; DRUG DETERMINATION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; GLUCOSE BLOOD LEVEL; IN VITRO STUDY; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; TRANSCRIPTION INITIATION; TRIACYLGLYCEROL BLOOD LEVEL;

ANIMALS; AZOLES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; FEMALE; HUMANS; HYDROGEN-ION CONCENTRATION; MICE; MICE, TRANSGENIC; PPAR ALPHA; PPAR GAMMA; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS;

EID: 60449088120     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.01.030     Document Type: Article

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36. PDB deposition number is 3BC5.
37. db/db mice, 8-10 weeks old, fed normal chow ad-lib, were orally dosed with compound or vehicle (5% NMP, 20% PEG-400, 20 mM aqueous sodium phosphate buffer, pH 8) once daily for 14 days. Blood samples were drawn from the tail vein on the 7th day after overnight fasting, and plasma analysis was performed on a COBAS automated analyzer. After 14 days, fasted animals were sacrificed. Blood and tissue samples were collected for clinical biochemistry analyses.