1080522-16-2

Upstream product

• 1080522-12-8 5-(2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy)-4-nitro-1H-indole-2-carboxylic acid 
• 1080522-10-6 5-(4-(carboxymethyl)-2-methoxyphenoxy)-4-nitro-1H-indole-2-carboxylic acid 
• 1080522-09-3 ethyl 5-(4-(2-ethoxy-2-oxoethyl)-2-methoxyphenoxy)-4-nitro-1H-indole-2-carboxylate 
• 1080522-13-9 methyl 2-(4-(2-carbamoyl-4-nitro-1H-indol-5-yloxy)-3 methoxyphenyl)acetate 

Downstream Products

• 1080522-18-4 C₂₅H₂₁Cl₂N₃O₇S 
• 1080521-11-4 2-(4-(2-cyano-4-(2,4-dichlorophenylsulfonamido)-1H-indol-5-yloxy)-3-methoxyphenyl)acetic acid 
• 1080522-19-5 methyl 2-(4-(2-cyano-4-(2,4-dichlorophenylsulfonamido)-1H-indol-5-yloxy)-3-methoxyphenyl)acetate 

Relevant academic research and scientific papers

Solving time-dependent CYP3A4 inhibition for a series of indole-phenylacetic acid dual antagonists of the PGD2 receptors CRTH2 and DP

Based on their structural similarity to previously described compound AMG 009, indole-phenyl acetic acids were proposed to be potent dual inhibitors of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2) and prostanoid D receptor (DP or DP1). This series was equipotent to AMG 009 in binding assays against both receptors but exhibited decreased serum shift. We discovered early in the optimization of these indole-phenylacetic acid compounds that they demonstrated CYP3A4 time-dependent inhibition (TDI). Hypothesizing that the source of TDI was the indole core we modified the 1,2,3-substitution to eventually afford a highly potent modulator of CRTH2 and DP which did not exhibit TDI.

COMPOUNDS AND METHODS USEFUL FOR TREATING ASTHMA AND ALLERGIC INFLAMMATION

Compounds, compositions and methods that are useful in the treatment of inflammatory and immune-related diseases and conditions are provided herein. In particular, the invention provides compounds which modulate the function and/or expression of proteins involved in atopic diseases, inflammatory conditions and cancer. The subject compounds are carboxylic acid derivatives.