1415253-93-8

Basic information

• Product Name: (S)-4'-((5-((1-(3-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid
• CAS NO: 1415253-93-8
• Molecular Weight: 558.72
• Mol File: 1415253-93-8.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: (S)-4'-((5-((1-(3-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-4'-((5-((1-(3-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid(1415253-93-8)
• EPA Substance Registry System: (S)-4'-((5-((1-(3-(tert-butyl)phenyl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid(1415253-93-8)

Safety Data

• Hazardous Substances Data: 1415253-93-8(Hazardous Substances Data)

Upstream product

• 23039-28-3 3-(tert-butyl)benzaldehyde 
• 1415256-20-0 1-((2'-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid 
• 1391435-10-1 (S)-1-(3-tert-butylphenyl)ethan-1-amine hydrochloride 
• 619-67-0 4-Hydrazinobenzoic acid 
• 14844-73-6 2,3-dimethyl-1H-indole-5-carboxylic acid 
• 1266458-65-4 allyl 2,3-dimethyl-1H-indole-5-carboxylate 

Relevant articles and documents

Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists

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.

N-BIPHENYLMETHYLINDOLE MODULATORS OF PPARG

The invention provides molecular entities that bind with high affinity to PPARG (PPAR3), inhibit kinase-mediated, e.g., cdk5-mediated, phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.