1. Co-crystal structure guided array synthesis of PPARgamma inverse agonists.
- Author
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Trump RP, Cobb JE, Shearer BG, Lambert MH, Nolte RT, Willson TM, Buckholz RG, Zhao SM, Leesnitzer LM, Iannone MA, Pearce KH, Billin AN, and Hoekstra WJ
- Subjects
- Crystallization, Ligands, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Structure, Oxazoles chemistry, PPAR gamma metabolism, Tyrosine chemistry, Tyrosine pharmacology, Oxazoles pharmacology, PPAR gamma antagonists & inhibitors, Tyrosine analogs & derivatives
- Abstract
PPARgamma-activating thiazolidinediones and carboxylic acids such as farglitazar exert their anti-diabetic effects in part in PPARgamma rich adipose. Both pro- and anti-adipogenic PPARgamma ligands promote glucose and lipid lowering in animal models of diabetes. Herein, we disclose representatives of an array of 160 farglitazar analogues with atypical inverse agonism of PPARgamma in mature adipocytes.
- Published
- 2007
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