197506-83-5

Usage

Uses

Used in Pharmaceutical Research:
3-FORMYL-1H-INDOLE-5-CARBOXYLIC ACID METHYL ESTER is used as a research compound for its potential biological activities, including its role as an inhibitor of the enzyme spermine synthase, which is involved in polyamine biosynthesis. This makes it a valuable tool for studying the regulation of polyamine metabolism and its implications in various diseases.
Used in Organic Synthesis:
3-FORMYL-1H-INDOLE-5-CARBOXYLIC ACID METHYL ESTER is used as a synthetic intermediate in the preparation of various organic compounds, leveraging its reactivity and structural features to facilitate the synthesis of complex molecules.
Used in Biochemistry:
3-FORMYL-1H-INDOLE-5-CARBOXYLIC ACID METHYL ESTER is used as a fluorescent probe for detecting zinc ions in biological samples. Its ability to selectively bind and fluoresce in the presence of zinc ions makes it a promising candidate for the development of biosensors and diagnostic tools in the field of biochemistry.
Overall, 3-FORMYL-1H-INDOLE-5-CARBOXYLIC ACID METHYL ESTER has potential applications in the fields of medicinal chemistry and biochemistry, making it an interesting target for further research and development.

InChI:InChI=1/C11H9NO3/c1-15-11(14)7-2-3-10-9(4-7)8(6-13)5-12-10/h2-6,12H,1H3

Upstream product

• 1011-65-0 5-methoxycarbonylindole 
• 68-12-2 N,N-dimethyl-formamide 
• 100-61-8 N-methylaniline 
• 100-97-0 hexamethylenetetramine 
• 298-12-4 Glyoxilic acid 
• 1670-81-1 1H-Indole-5-carboxylic acid 

Downstream Products

• 1283707-04-9 C₂₂H₁₆N₄O₃S 
• 1283707-06-1 C₂₃H₁₉N₃O₅S 
• 1283706-87-5 C₂₂H₁₆N₄O₄ 
• 1283706-71-7 C₁₉H₁₄N₂O₃ 
• 1283706-81-9 methyl 3-formyl-1-(4-(methoxycarbonyl)benzyl)-1H-indole-5-carboxylate 

Relevant academic research and scientific papers

Triphenylphosphine/1,2-Diiodoethane-Promoted Formylation of Indoles with N, N -Dimethylformamide

Despite intensive studies on the synthesis of 3-formylindoles, it is still highly desirable to develop efficient methods for the formylation of indoles, due to the shortcomings of the reported methods, such as inconvenient operations and/or harsh reaction conditions. Here, we describe a Ph3P/ICH2CH2I-promoted formylation of indoles with DMF under mild conditions. A Vilsmeier-type intermediate is readily formed from DMF promoted by the Ph3P/ICH2CH2I system. A onestep formylation process can be applied to various electron-rich indoles, but a hydrolysis needs to be carried out as a second step in the case of electron-deficient indoles. Convenient operations make this protocol attractive.

C3-Formylation of Indoles in Continuous Flow

We have developed a continuous flow C3-formylation technique for indoles using hexamethylenetetramine (HMTA) and iodine. A mixed solvent system of DMF–H2O (1:1, vol/vol) completely dissolves reagents and prevents clogging of microchannels during fluid flow. The continuous flow technique provides maximized mixing and excellent heat transfer efficiency. Thus, flow chemistry accelerates the rate of C3-formylation of indoles in the absence of a strong acid, base, or metal catalyst. We show that high yields of C3-formylated indoles (up to 83%) can be obtained at 150°C when the residence time is as low as 8 min.

Discovery of Novel Polycyclic Heterocyclic Derivatives from Evodiamine for the Potential Treatment of Triple-Negative Breast Cancer

Evodiamine (Evo) is a quinazolinocarboline alkaloid found in Evodia rutaecarpa and exhibits moderate antiproliferative activity. Herein, we report using a scaffold-hopping approach to identify a series of novel polycyclic heterocyclic derivatives based on Evo as the topoisomerase I (Top1) inhibitor for the treatment of triple-negative breast cancer (TNBC), which is an aggressive subtype of breast cancer with limited treatment options. The most potent compound 7f inhibited cell growth in a human breast carcinoma cell line (MDA-MB-231) with an IC50 value of 0.36 μM. Further studies revealed that Top1 was the target of 7f, which directly induced irreversible Top1-DNA covalent complex formation or induced an oxidative DNA lesion through an indirect mechanism mediated by reactive oxygen species. More importantly, in vivo studies showed that 7f exhibited potent antitumor activity in a TNBC-patient-derived tumor xenograft model. These results suggest that compound 7f deserves further investigation as a promising candidate for the treatment of TNBC.

Discovery of a Class of Potent and Selective Non-competitive Sentrin-Specific Protease 1 Inhibitors

Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors.

Synthesis of 3-Formylindoles via Electrochemical Decarboxylation of Glyoxylic Acid with an Amine as a Dual Function Organocatalyst

A new method for 3-formalytion of indoles has been developed through electrochemical decarboxylation of glyoxylic acid with the amine as a dual function organocatalyst. The amine facilitated both the electrochemical decarboxylation and the nucleophilic reaction efficiently, whose loading can be as low as 1 mol %. This protocol has a broad range of functional group tolerance under ambient conditions. The gram-scale experiment has shown great potential in the synthetic application of this strategy.

Search for a 5-CT alternative. In vitro and in vivo evaluation of novel pharmacological tools: 3-(1-alkyl-1H-imidazol-5-yl)-1H-indole-5-carboxamides, low-basicity 5-HT7 receptor agonists

Close structural analogues of 5-carboxamidotryptamine (5-CT) based on the newly discovered indole-imidazole scaffold were synthesized and evaluated to search for a 5-HT7 receptor agonist of higher selectivity. In vitro drug-likeness studies and in vivo pharmacological evaluation of potent and selective low-basicity 5-HT7 receptor agonists, previously published 7 (3-(1-ethyl-1H-imidazol-5-yl)-1H-indole-5-carboxamide, AH-494) and 13 (3-(1-methyl-1H-imidazol-5-yl)-1H-indole-5-carboxamide), have supported their usefulness as pharmacological tools. Comprehensive in vitro comparison studies between 7, 13 and the commonly used 5-CT showed their very similar ADMET properties. Compound 7 at 1 mg kg?1 reversed MK-801-induced disruption in novel object recognition in mice and alleviated stress-induced hyperthermia (SIH) at high doses. Taking into account both in vitro and in vivo data, 7 and 13 may be considered as alternatives to 5-CT as pharmacological tools with important additional benefit associated with their low-basicity: high selectivity over 5-HT1AR.

Synthesis of polycyclic spirooxindoles via an asymmetric catalytic one-pot stepwise Aldol/chloroetherification/aromatization procedure

A general method for the synthesis of chiral pentacyclic spirooxindoles containing a tetrahydropyrano[2,3-b]indole scaffold through a one-pot stepwise sequence from 3-(3-indolomethyl)oxindole, paraformaldehyde and NCS is reported. Furthermore, the pentacyclic spirooxindoles could be transformed to bispirooxindole and other structurally diverse spirocyclic oxindoles.

BENZOPYRAZOLE COMPOUNDS AND ANALOGUES THEREOF

Disclosed are compounds of formula (I), and pharmaceutically acceptable salts thereof. The compounds are inhibitors of the complement system. Also provided are pharmaceutical compositions comprising a compound of formula (I), and methods involving use of the compounds and compositions in the treatment and prevention of diseases and conditions characterized by aberrant complement system activity.

Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens

The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents.

Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis

An unprecedented tandem N-alkylation-ionic aza-Cope (or Claisen) rearrangement-hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N-alkylation and subsequent microwave-irradiated ionic aza-Cope rearrangement-hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2-reverse quaternary-centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza-Cope rearrangement reaction proceeds highly regioselectively to give the quaternary-centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3-methylene-2,3-dihydro-1Hindole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2-reverse prenylated indoles, such as indolines, indolefused sultams and lactams, and the natural product bruceolline D.