50536-58-8

Upstream product

• 16732-80-2 4-methyl-1H-indole-2-carboxylic acid ethyl ester 
• 529-20-4 2-methylphenyl aldehyde 
• 81803-45-4 ethyl 2-azido-3-(2-methylphenyl)propenoate 
• 1857296-39-9 methyl 5-bromo-4-methyl-1H-indole-2-carboxylate 
• 83647-40-9 3-bromo-2-methylbenzaldehyde 
• 83647-43-2 3-bromo-2-methylbenzyl alcohol 
• 76006-33-2 3-bromo-2-methylbenzoic acid 
• 671215-69-3 ethyl 5-bromo-4-methyl-1H-indole-2-carboxylate 

Downstream Products

• 671215-70-6 4-Methyl-1H-indole-5-carbonitrile 

Relevant academic research and scientific papers

Regioselective Functionalization of 4-Methyl-1H-indole for Scalable Synthesis of 2-Cyano-5-formyl-4-methyl-1H-indole

We report a five-step synthesis of 2-cyano-5-formyl-4-methyl-1H-indole through sequential functionalization of readily available 4-methyl-1H-indole. Cyano and aldehyde functionalities are regioselectively installed at the 2 and 5 position, respectively. T

METHODS OF PROMOTING BETA CELL PROLIFERATION

The present disclosure provides methods of promoting proliferation of a pancreatic cell. The methods are useful for the treatment of diabetes and other diseases characterized by impaired glucose tolerance.

THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF

The present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including but not limited to MLL1, MLL2 and MLL-fusion oncoproteins. Compounds of the disclosure may be used

Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL)

Development of potent small molecule inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications.

Indolyl derivatives

Compounds of formula I are provided as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R8, A, A1 and n have the significance indicated in the specification.