1338259-05-4

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
4′-[[2,3-Dimethyl-5-[[[(1S)-1-(4-nitrophenyl)ethyl]amino]carbonyl]-1H-indol-1-yl]methyl][1,1′-Biphenyl]-2-carboxylic acid is utilized as a compound of interest in pharmaceutical research and drug development. Its complex structure and particular arrangement of functional groups make it a promising candidate for the discovery of new therapeutic agents.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 4′-[[2,3-Dimethyl-5-[[[(1S)-1-(4-nitrophenyl)ethyl]amino]carbonyl]-1H-indol-1-yl]methyl][1,1′-Biphenyl]-2-carboxylic acid is used for exploring its potential biological activity. 4′-[[2,3-Dimethyl-5-[[[(1S)-1-(4-nitrophenyl)ethyl]amino]carbonyl]-1H-indol-1-yl]methyl][1,1′-Biphenyl]-2-carboxylic acid's unique features and functional groups may contribute to the development of novel drugs with specific therapeutic targets.

Upstream product

• 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 
• 114772-40-6 4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester 
• 21523-62-6 2,3-dimethylindole-5-carboxylic acid ethyl ester 
• 1415256-20-0 1-((2'-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid 
• 1220018-34-7 ethyl 1-[(2'-{[(tert-butyl)oxy]carbonyl}-4-biphenyl)methyl]-2,3-dimethyl-1H-indole-5-carboxylate 

Relevant academic research and scientific papers

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.

PPARG MODULATORS FOR TREATMENT OF OSTEOPOROSIS

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.

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.

Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation

PPARγ is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone. These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPARγ-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARγ by Cdk5 (ref. 2). Here we describe novel synthetic compounds that have a unique mode of binding to PPARγ, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPARγ drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARγ. 2011 Macmillan Publishers Limited. All rights reserved.