1467059-98-8

Basic information

• Product Name: 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde
• Synonyms: 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde
• CAS NO: 1467059-98-8
• Molecular Weight: 260.038
• Mol File: 1467059-98-8.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde(1467059-98-8)
• EPA Substance Registry System: 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde(1467059-98-8)

Safety Data

• Hazardous Substances Data: 1467059-98-8(Hazardous Substances Data)

Upstream product

• 126674-93-9 4,6-difluoro-1H-indole-2,3-dione 
• 1154742-51-4 5-bromo-4,6-difluoro-1H-indole 
• 3724-43-4 Vilsmeier reagent 
• 30354-18-8 N,N-dimethyl(methylene)ammonium chloride 
• 1467059-97-7 5-bromo-4,6-difluoroindoline 
• 199526-98-2 4,6-difluoroindoline 
• 199526-97-1 4,6-difluoro-1H-indole 
• 1467060-37-2 4-bromo-3,5-difluoro-2-[(trimethylsilyl)ethynyl]aniline 
• 1467060-36-1 4-bromo-3,5-difluoro-2-iodoaniline 
• 203302-95-8 4-bromo-3,5-difluorophenylamine 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1467060-39-4 4,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carbaldehyde 
• 1467057-66-4 4,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carboxylic acid 
• 1467060-43-0 4,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde 
• 1467057-69-7 4,6-difluoro-5-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-1H-indole-3-carboxylic acid 
• 1467060-46-3 4,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carbaldehyde 
• 1467057-76-6 4,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carboxylic acid 
• 1467060-50-9 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carbaldehyde 
• 1467057-80-2 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carboxylic acid 
• 1467060-53-2 4,6-difluoro-5-[4-(3-hydroxypropoxy)phenyl]-1H-indole-3-carbaldehyde 
• 1467057-85-7 4,6-difluoro-5-[4-(3-hydroxypropoxy)phenyl]-1H-indole-3-carboxylic acid 
• 1467057-35-7 4,6-difluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid 
• 1467059-99-9 4,6-difluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehyde 

Relevant articles and documents

Evolution of the Synthesis of AMPK Activators for the Treatment of Diabetic Nephropathy: From Three Preclinical Candidates to the Investigational New Drug PF-06409577

Indole acids 1, 2, and 3 are potent 5′-adenosine monophosphate-activated protein kinase (AMPK) activators for the potential treatment of diabetic nephropathy. Compounds 1-3 were scaled to supply material for preclinical studies, and indole 3 was selected for advancement to first-in-human clinical trials and scaled to kilogram quantities. The progression of the synthesis strategy for these AMPK activators is described, as routes were selected for efficient structure-activity relationship generation and then improved for larger scales. The developed sequences employed practical isolations of intermediates and APIs, reproducible cross-coupling, hydrolysis, and other transformations, and enhanced safety and purity profiles and led to the production of 40-50 g of 1 and 2 and 2.4 kg of 3. Multiple polymorphs of 3 were observed, and conditions for the reproducible formation of crystalline material suitable for clinical development were identified.

INDOLE AND INDAZOLE COMPOUNDS THAT ACTIVATE AMPK

The present invention relates to indole and indazole compounds of Formula (I) that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.