16136-58-6

Usage

Uses

1. Used in Pharmaceutical Industry:
1-Methylindole-2-carboxylic acid is used as a reactant for the preparation of keto-indoles, which are novel indoleamine 2,3-dioxygenase (IDO) inhibitors. These inhibitors have potential applications in the treatment of various diseases, including cancer and neurodegenerative disorders.
2. Used in Antitumor Applications:
1-Methylindole-2-carboxylic acid is used as a reactant for the synthesis of fenbufen and ethacrynic acid derivatives. These derivatives are potential antitumor agents that can be employed in the development of new cancer treatments.
3. Used in Organic Synthesis:
1-Methylindole-2-carboxylic acid is used as a reactant for diastereoselective synthesis of vinylated heterocycles via ruthenium-catalyzed oxidative vinylation with alkenes. This process allows for the creation of complex molecular structures with potential applications in various industries, including pharmaceuticals and materials science.
4. Used in Halogenation Reactions:
1-Methylindole-2-carboxylic acid is used as a reactant for the synthesis of 2,3-dihalo indoles via hypervalent iodine mediated decarboxylative halogenation. These halogenated indoles can be utilized as intermediates in the synthesis of various pharmaceutical compounds.
5. Used in Enzyme Inhibition:
1-Methylindole-2-carboxylic acid is used as a reactant for the preparation of α-ketoamides, which are cathepsin S inhibitors. These inhibitors have potential applications in the treatment of tumor invasion and angiogenesis, as well as other diseases where cathepsin S plays a role.
6. Used in Bacterial Inhibition:
1-Methylindole-2-carboxylic acid is used as a reactant for the preparation of anthranilic acid mimics, which are bacterial translation inhibitors. These inhibitors can be employed in the development of new antibiotics to combat bacterial infections.

InChI:InChI=1/C10H9NO2/c1-11-8-5-3-2-4-7(8)6-9(11)10(12)13/h2-6H,1H3,(H,12,13)

Upstream product

• 603-76-9 1-methylindole 
• 3265-26-7 2-(methyl-phenyl-hydrazono)-propionic acid 
• 90-12-0 1-Methylnaphthalene 
• 13867-00-0 2-(methyl-phenyl-hydrazono)-propionic acid ethyl ester 
• 3265-26-7 2-(Methyl-phenyl-hydrazono)-propionic acid 
• 37493-34-8 methyl 1-methyl-1H-indole-2-carboxylate 
• 18450-24-3 ethyl N-methylindole-2-carboxylate 
• 109-72-8 n-butyllithium 
• 60-29-7 diethyl ether 
• 124-38-9 carbon dioxide 
• 128746-62-3 2,3-dibromo-1-methyl-1H-indole 
• 545432-27-7 2-(N,N-dimethylhydrazinecarbonyl)-1-methylindole 
• 932-32-1 N-methyl-2-chloroaniline 
• 127-17-3 2-oxo-propionic acid 

Downstream Products

• 603-76-9 1-methylindole 
• 1485-22-9 (1-methyl-1H-indol-2-yl)-methanol 
• 37493-34-8 methyl 1-methyl-1H-indole-2-carboxylate 
• 41979-55-9 N,N-dimethyl-1-methylindole-2-carboxamide 
• 18450-24-3 ethyl N-methylindole-2-carboxylate 
• 39167-76-5 N-phenyl-1-methyl-1H-indole-2-carboxamide 
• 56297-43-9 1-methyl-1H-indole-2-carboxamide 
• 103373-07-5 1,3-Dihydro-3-(RS)-(1-methylindole-2-carbonylamino)-5-(2-fluorophenyl)-2H-1,4-benzodiazepine-2-one 
• 118618-61-4 1-methyl-1H-indole-2-carbonyl chloride 
• 16498-68-3 1-(1-methyl-1H-indol-2-yl)ethanone 
• 1000069-68-0 N-[2-(tert-butylthio)phenyl]-1-methyl-1H-indole-2-carboxamide 

Relevant academic research and scientific papers

A flexible, palladium-catalyzed indole and azaindole synthesis by direct annulation of chloroanilines and chloroaminopyridines with ketones

The "ringmaster" [Pd(tBu3P)2] serves as the catalyst in the direct synthesis of indoles by annulation of ortho-chloroanilines with ketones (see picture). This versatile method can be used to synthesize a variety of functionalized indoles and azaindoles. DMA = dimethylacetarnide.

Design and synthesis of thiadiazolo-carboxamide bridged β-carboline-indole hybrids: DNA intercalative topo-IIα inhibition with promising antiproliferative activity

The conjoining of salient pharmacophoric properties directing the development of prominent cytotoxic agents was executed by constructing thiadiazolo-carboxamide bridged β-carboline-indole hybrids. On the evaluation of in vitro cytotoxic potential, 12c exhibited prodigious cytotoxicity among the synthesized new molecules 12a–k, with an IC50 50 value of 2.82 ± 0.10 μM. Besides, another compound 12a also displayed impressive cytotoxicity against A549 cell line (IC50: 3.00 ± 1.40 μM). Further target-based assay of these two compounds 12c and 12a revealed their potential as DNA intercalative topoisomerase-IIα inhibitors. Additionally, the antiproliferative activity of compound 12c was measured in A549 cells by traditional apoptosis assays revealing the nuclear, morphological alterations, and depolarization of membrane potential in mitochondria and externalization of phosphatidylserine in a concentration-dependent manner. Cell cycle analysis unveiled the G0/G1 phase inhibition and wound healing assay inferred the inhibition of in vitro cell migration by compound 12c in lung cancer cells. Remarkably, the safety profile of compound 12c was disclosed by screening against normal human lung epithelial cell line (BEAS-2B: IC50: 71.2 ± 7.95 μM) with a selectivity index range of 14.9–25.26. Moreover, Molecular modeling studies affirm the intercalative binding of compound 12c and 12a in the active pocket of topo-IIα. Furthermore, in silico prediction of physico-chemical parameters divulged the propitious drug-like properties of the synthesized derivatives.

Friedel-Crafts Chemistry. Part 53. Divergent and Diversity-Oriented Synthesis of Condensed Indole Scaffolds via Friedel-Crafts Ring Closure Approach

A series of indole-fused medium-sized N-heterocyclic systems 10a-h were prepared from laboratory-synthesized indole-based esters 9a-h via intramolecular Friedel-Crafts cyclizations induced by both trifluoromethanesulfonic acid and AlCl3/CH

Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis

Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of BI-4916, a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD+)-competitive PHGDH inhibitor BI-4924, which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening, a subsequent hit optimization using structure-based drug design was conducted to deliver a single-digit nanomolar lead series and to improve potency by 6 orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD+

Asymmetric Nazarov Cyclizations Catalyzed by Chiral-at-Metal Complexes

The application of Lewis acidic chiral-at-metal complexes of iridium(III) and rhodium(III) as catalysts for the asymmetric polarized Nazarov cyclization of dihydropyran- and indole-functionalized α-unsaturated β-ketoesters is reported (overall 24 examples). For both substrate classes, catalyst loadings of 2 mol% were found to be sufficient for achieving high yields and high stereoselectivities. The cyclized dihydropyran products were isolated in 85–98% yield, with 89%–>99% ee, and trans/cis ratios of 15:1–50:1 (9 examples). The cyclized indole products were typically isolated in more than 70% yield and in up to 93% yield, typically with more than 90% ee and in up to 97% ee, and trans/cis ratios of 12:1–28:1 (15 examples). (Figure presented.).

A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids

Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.

Synthesis of 3,3-Dihalo-2-oxindoles from 2-Substituted Indoles via Halogenation–Decarboxylation/Desulfonamidation–Oxidation Process

A novel one-pot reaction which combines halogenation, decarboxylation/desulfonamidation with oxidation has been developed. Diverse valuable 3,3-dihalo-2-oxindole compounds can be produced rapidly and safely with isolated yields of up to 98% under mild conditions. (Figure presented.).

Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole derivatives: A new method for synthesis pyranoindoles

A direct and highly stereoselective approach for the synthesis of Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A variety of pyranoindoles were obtained in 44-93% yields. Moreover, a more convenient synthesis of pyranoindoles starting from terminal alkyne was realized via a Cu-Rh sequentially catalyzed one-pot cascade reaction.

Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl Enol Ethers

Visible-light-promoted oxidative [4 + 2] cycloadditions of μ,3-unsaturated silyl enol ethers have been developed to efficiently and diastereoselectively construct polycyclic skeletons under mild conditions. The diastereoselectivities were dependent on the stereoconfiguration of silyl enol ether, substitutions on the link, as well as electric properties of substitutions on aryl rings. The intermediates could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron oxidation of the silyl enol ether.

Piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides: Novel 5-HT3 receptor antagonists with antidepressant-like activity

Series of piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides were designed using a ligand-based approach with consideration of the pharmacophoric requirements for 5-HT3 receptor antagonists. The title carboxamides were synthesized using appropriate synthetic routes. Initially, the 5-HT3 receptor antagonistic activity of all the compounds was determined on isolated guinea pig ileum tissue against the 5-HT3 agonist, 2-methyl-5-hydroxytryptamine, which was denoted in the form of pA2 values. The structure-activity relationship regarding the influence of the aromatic part and basic moiety as features in the 5-HT3 pharmacophore was derived. Among all the compounds screened, the piperazine derivatives of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h exhibited prominent 5-HT3 receptor antagonism with pA2 values of 7.5 and 7.3, respectively. Subsequent investigation of the antidepressant activities of selected compounds in the mouse forced swim test (FST) led to the identification of the piperazine analogs of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h as the most promising compounds. Both 13i and 8h demonstrated significant reduction in the duration of immobility as compared to the control. Importantly, none of the tested compounds affected the baseline locomotion of mice at the tested dose levels.