244090-32-2

Upstream product

• 942-24-5 3-methoxycarbonylindole 
• 591-50-4 iodobenzene 
• 108-86-1 bromobenzene 
• 67-56-1 methanol 
• 16096-33-6 1-phenyl-1H-indole 
• 120-72-9 indole 

Downstream Products

• 244090-34-4 1-phenyl-1H-indole-3-carboxylic acid 

Relevant academic research and scientific papers

Development and Profiling of Inverse Agonist Tools for the Neuroprotective Transcription Factor Nurr1

The ligand-sensing transcription factor nuclear receptor related 1 (Nurr1) evolves as an appealing target to treat neurodegenerative diseases. Despite its therapeutic potential observed in various rodent models, potent modulators for Nurr1 are lacking as pharmacological tools. Here, we report the structure-activity relationship and systematic optimization of indole-based inverse Nurr1 agonists. Optimized analogues decreased the receptor's intrinsic transcriptional activity by up to more than 90% and revealed preference for inhibiting Nurr1 monomer activity. In orthogonal cell-free settings, we detected displacement of NCoRs and disruption of the Nurr1 homodimer as molecular modes of action. The inverse Nurr1 agonists reduced the expression of Nurr1-regulated genes in T98G cells, and treatment with an inverse Nurr1 agonist mimicked the effect of Nurr1 silencing on interleukin-6 release from LPS-stimulated human astrocytes. The indole-based inverse Nurr1 agonists valuably extend the toolbox of Nurr1 modulators to further probe the role of Nurr1 in neuroinflammation, cancer, and beyond.

Hydroxamic acids block replication of hepatitis c virus

Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be either relatively toxic or ineffective, structure-activity relationship (SAR) studies on cinnamic hydroxamic acid and benzo[b]thiophen-2-hydroxamic acid gave rise to compounds 22 and 53, which showed potent and selective anti-HCV activity and therefore are promising starting points for further structural optimization and mechanistic studies.

Selective copper catalysed aromatic N-arylation in water

4,7-Dipyrrolidinyl-1,10-phenanthroline (DPPhen) was identified as an efficient ligand for copper catalysed selective aromatic N-arylation in water. N-Arylation of indoles, imidazoles and purines proceeds with moderate to excellent yields and complete selectivity over aliphatic amines. Aqueous medium and the possibility for low metal and ligand loadings give the process a benign environmental profile.

OXADIAZOLE DERIVATIVES AND THEIR USE AS NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS

Oxadiazole derivatives of formula (I) where ring A is a bicyclic or tricyclic system. Claimed compounds are active on nicotinic acetylcholine receptors (nAChRs), and are useful to treat neurological, psychiatric, and gastrointestinal disorders, as well as sepsis and obesity.

The copper-catalyzed N-arylation of indoles

A general method for the N-arylation of indoles using catalysts derived from Cul and trans-1,2-cyclohexanediamine (1a), trans-N,N′-dimethyl-1,2-cyclohexanediamine (2a), or N,N′-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.

Replacement of the quinoline system in 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonists

Results from a medicinal chemistry approach aimed at replacing the quinoline ring system in the potent and selective human neurokinin-3 (hNK-3) receptor antagonists 1-4 of general formula I are discussed. The data give further insight upon the potential NK-3 pharmacophore. In particular, it is highlighted that both the benzene-condensed ring and the quinoline nitrogen are crucial determinants for optimal binding affinity to the hNK-3 receptor. Some novel compounds maintained part of the binding affinity to the receptor (5, 6, 10 and 13) and compound 5, featuring the naphthalene ring system, appears to be suitable for further modifications: it offers the option to introduce electron-withdrawing groups at position 2 and 4, conferring on the ring an overall electron-deficiency similar to that of the quinoline.