1415255-72-9Relevant academic research and scientific papers
Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists
Asteian, Alice,Blayo, Anne-Laure,He, Yuanjun,Koenig, Marcel,Shin, Youseung,Kuruvilla, Dana S.,Corzo, Cesar A.,Cameron, Michael D.,Lin, Li,Ruiz, Claudia,Khan, Susan,Kumar, Naresh,Busby, Scott,Marciano, David P.,Garcia-Ordonez, Ruben D.,Griffin, Patrick R.,Kamenecka, Theodore M.
, p. 998 - 1003 (2015/09/22)
The thiazolidinediones (TZD) typified by rosiglitazone are the only approved therapeutics targeting PPARγ for the treatment of type-2 diabetes (T2DM). Unfortunately, despite robust insulin sensitizing properties, they are accompanied by a number of severe side effects including congestive heart failure, edema, weight gain, and osteoporosis. We recently identified PPARγ antagonists that bind reversibly with high affinity but do not induce transactivation of the receptor, yet they act as insulin sensitizers in mouse models of diabetes (SR1664).1 This Letter details our synthetic exploration around this novel series of PPARγ antagonists based on an N-biphenylmethylindole scaffold. Structure-activity relationship studies led to the identification of compound 46 as a high affinity PPARγ antagonist that exhibits antidiabetic properties following oral administration in diet-induced obese mice.
PPARG MODULATORS FOR TREATMENT OF OSTEOPOROSIS
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Page/Page column 419, (2015/11/09)
The invention provides methods of treatment of a progressive bone disease, such as osteoporosis, Paget's Disease, multiple myeloma, or hyperparathyroidism, comprising administration of an effective amount of a non-agonist PPARG modulator to a patient afflicted with the disease.
