105776-11-2

Upstream product

• 105776-30-5 dimethyl 4,6-dimethoxyindole-2,3-dicarboxylate 
• 127220-99-9 ethyl 4,6-dimethoxy-1H-indole-2-carboxylate 
• 888723-69-1 ethyl (3,5-dimethoxyphenyl)glycinate 
• 10272-07-8 3.5-dimethoxyaniline 
• 105776-13-4 4,6-dimethoxy-1H-indole-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Synthesis of 4,6-Dimethoxyindoles

Syntheses are described for nine new 4,6-dimethoxyindoles, incorporating phenyl, pyridin-2-yl, methoxycarbonyl, carboxy and methyl groups in the 2- and/or 3-positions.

Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection

Our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-TB activity at both an in vitro and in vivo level. Based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter MmpL3 as the likely target of these compounds. In the present work, we now further elaborate on the SAR of these compounds, which has led in turn to the identification of a new analog, 4,6-difluoro-N-((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)-1H-indole-2-carboxamide (26), that shows excellent activity against drug-sensitive (MIC = 0.012 μM; SI ≥ 16000), multidrug-resistant (MDR), and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains, has superior ADMET properties, and shows excellent activity in the TB aerosol lung infection model. Compound 26 is also shown to work in synergy with rifampin. Because of these properties, we believe that indolecarboxamide 26 is a possible candidate for advancement to human clinical trials.

Both 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones and 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones are light-dependent tumor necrosis factor-α antagonists

Based on the realization that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones are tumor necrosis factor-α antagonists, we discovered two additional classes of antagonists: 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones (via rational design) and 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (via computer-guided screening). Chemical modification of the lead structures showed that the structure-activity relationship profiles for both of these series were dependent on the electronic properties of the molecules. Subsequent studies showed that they were light-dependent inhibitors.

Small molecule inhibitors of bacterial transcription complex formation

Knoevenagel condensation was employed to generate a set of molecules potentially capable of inhibiting the RNA polymerase-σ70/σA interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library of structurally diverse compounds was examined by enzyme-linked immunosorbent assay (ELISA) to assess the inhibition of the targeted protein–protein interaction. Inhibition of bacterial growth was also evaluated using Bacillus subtilis and Escherichia coli cultures. The structure–activity relationship studies demonstrated the significance of particular structural features of the synthesized molecules for RNA polymerase-σ70/σA interaction inhibition and antibacterial activity. Docking was investigated as an in silico method for the further development of the compounds.

Indolecarboxylic compounds for inducing/stimulating hair growth and/or retarding hair loss

Indolecarboxylic acid compounds and derivatives thereof, notably 4,6-dimethoxyindole-2-carboxylic acid and derivatives thereof, are especially useful for inducing/stimulating mammalian hair growth and/or preventing/retarding mammalian hair loss.