6625-96-3

Usage

Uses

Used in Laboratory Research:
5-Nitro-1H-indole-3-carbaldehyde is used as a chemical compound in laboratory research for [application reason]. The specific applications and reasons for its use in this context are currently unclear and may require further study to understand its potential benefits and limitations in various research areas.

InChI:InChI=1/C8H5N3O3/c12-4-8-6-3-5(11(13)14)1-2-7(6)9-10-8/h1-4H,(H,9,10)

Upstream product

• 110-18-9 N,N,N,N,-tetramethylethylenediamine 
• 6146-52-7 5-nitroindole 
• 100-97-0 hexamethylenetetramine 
• 50-00-0 formaldehyd 
• 298-12-4 Glyoxilic acid 
• 487-89-8 Indole-3-carboxaldehyde 
• 3414-64-0 N,N-dimethyl-5-nitro-1H-indole-3-methanamine 
• 93-61-8 N-methyl-N-phenylformamide 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1195784-95-2 C₁₈H₁₃N₅O₂ 
• 7147-14-0 5-nitro-1H-indole-3-carbonitrile 
• 6146-52-7 5-nitroindole 
• 1346151-08-3 (Z)-6-hydroxy-2-[(5-nitro-1H-indol-3-yl)methylene]benzofuran-3(2H)-one 
• 1346151-09-4 tert-butyl (Z)-4-({6-hydroxy-2-[(5-nitro-1H-indol-3-yl)methylene]-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate 
• 1356239-25-2 C₂₃H₁₈N₄O₅S 
• 1508307-37-6 (E)-N-(4-tert-butylphenyl)-2-methyl-3-(5-nitro-1H-indol-3-yl)acrylamide 
• 1494469-86-1 2-(5-nitro-1H-indol-3-ylmethylene)-5,5-dimethyl-cyclohexane-1,3-dione 
• 1494469-90-7 2-(5-nitro-1H-indol-3-ylmethylene)-cyclohexane-1,3-dione 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of N-(3-cyano-1H-indol-5/6-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamides and 5-(6-oxo-1,6-dihydropyrimidin-2-yl)-1H-indole-3-carbonitriles as novel xanthine oxidase inhibitors

Xanthine oxidase (XO) has been an important target for the treatment of hyperuricemia and gout. The analysis of potential interactions of pyrimidinone and 3-cyano indole pharmacophores present in the corresponding reported XO inhibitors with parts of the XO active pocket indicated that they both can be used as effective fragments for the fragment-based design of nonpurine XO inhibitors. In this paper, we adopted the fragment-based drug design strategy to link the two fragments with an amide bond to design the type 1 compounds 13a–13w,14c, 14d, 14f, 14g, 14j, 14k, and 15g. Compound 13g displayed an evident XO inhibitory potency (IC50 = 0.16 μM), which was 52.3-fold higher than that of allopurinol (IC50 = 8.37 μM). For comparison, type 2 compounds 5-(6-oxo-1,6-dihydropyrimidin-2-yl)-1H-indole-3-carbonitriles (25c–25g) were also designed by linking the two fragments with a single bond directly. The results showed that compound 25c from the latter series displayed the best inhibitory potency (IC50 = 0.085 μM), and it was 98.5-fold stronger than that of allopurinol (IC50 = 8.37 μM). These results suggested that amide and single bonds were applicable for linking the two fragments together to obtain potent nonpurine XO inhibitors. The structure–activity relationship results revealed that hydrophobic groups at N-atom of the indole moiety were indispensable for the improvement of the inhibitory potency in vitro against XO. In addition, enzyme kinetics studies suggested that compounds 13g and 25c, as the most promising XO inhibitors for the two types of target compounds, acted as mixed-type inhibitors for XO. Moreover, molecular modeling studies suggested that the pyrimidinone and indole moieties of the target compounds could interact well with key amino acid residues in the active pocket of XO. Furthermore, in vivo hypouricemic effect demonstrated that compounds 13g and 25c could effectively reduce serum uric acid levels at an oral dose of 10 mg/kg. Therefore, compounds 13g and 25c could be potential and efficacious agents for the treatment of hyperuricemia and gout.

Trichloroisocyanuric acid (TCCA) and carboxamide interactions in TCCA/NaNO2 triggered nitration of pyrrole and indole in aqueous aprotic media: A kinetic correlation of solvent properties with reactivity

This study deals with the trichloroisocyanuric acid (TCCA) interactions with carboxamides like formamide (FMA), N,N′-dimethyl formamide (DMF), and N,N′-dimethyl acetamide (DMA) interactions during the nitration of heterocyclic compounds (HC) like pyrrole and indole in the presence of excess of [NaNO2] over the concentrations of all other reactants. All the reactions were performed in aqueous acetonitrile media containing carboxamide under acid-free conditions. Kinetics of the reactions revealed first order in [nitrating agent] and [HC] under otherwise similar conditions. To gain an insight into the reactive species and role of added carboxamide (FAA, DMF, DMA, etc.), the observed rates of the nitration reaction (log k) were analyzed as a function of (1/D), ([D ? 1]/[2D + 1]), mole fraction (nx), and volume (%) of carboxamide, 1/viscosity, density refractive index function), and Hildebrand solubility parameter plots. Linear regression analysis gave very good correlation coefficients (R2 values), which indicate the importance of several solvent properties in addition to the role of dielectric constant (D) of the reaction media. Multiple linear solvent energy relationships suggested by Abraham, Koppel, Palm, and Taft also afforded very good correlation coefficient (R2 values), showing the importance of cumulative effect of solvent properties. Besides these features, the negative entropies of activation (?S#) suggest greater solvation in the transition state. Isokinetic temperature (β) values for different protocols were very close to the experimental temperature range (303-323 K), indicating the importance of both enthalpy and entropy factors in controlling the reaction.

N-(indol-5-yl) bicyclic aromatic amide compound as well as preparation method and application thereof

The invention belongs to the field of medicines, and relates to an N-(indole-5-yl) bicyclic aromatic amide compound as well as a preparation method and application thereof. The structural general formula of the N-(indol-5-yl) bicyclic aromatic amide compound is shown in the specification. A pharmaceutical composition comprises the N-(indol-5-yl) bicyclic aromatic amide compound, a pharmaceutically acceptable salt, a hydrate or a solvate of the N-(indol-5-yl) bicyclic aromatic amide compound, and a pharmaceutically acceptable carrier. The invention further discloses application of the N-(indol-5-yl) bicyclic aromatic amide compound or the pharmaceutically acceptable salt, hydrate or solvate thereof or the pharmaceutical composition in preparation of anti-hyperuricemia and anti-gout drugs. Tests prove that the compound shows a good effect in an in-vitro xanthine oxidase inhibitory activity test. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.

N-(3-cyano-1H-indol-5-yl)isonicotinamide and N-(3-cyano-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamide derivatives: Novel amide-based xanthine oxidase inhibitors

Our previous work demonstrated that amide is an efficient linker to explore chemical space of xanthine oxidase (XO) inhibitors that are entirely different from febuxostat and topiroxostat. In this effort, with 3-cyano-1H-indol-5-yl as a key moiety, two series of amide-based XO inhibitors, N-(3-cyano-1H-indol-5-yl)isonicotinamides (2a-w) and N-(3-cyano-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamides (3a-i), were designed and synthesized. The structure-activity relationship investigation identified N-(3-cyano-1-cyclopentyl-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamide (3i, IC50 = 0.62 μM) as the most promising compound, with 14.4-fold higher in vitro inhibitory potency than allopurinol (IC50 = 8.91 μM). Molecular simulations provided reasonable interaction modes for the representative compounds. Furthermore, in vivo activity evaluation demonstrated that compound 3i (oral dose of 12.8 mg/kg) has obviously hypouricemic effect on a potassium oxonate induced hyperuricemic rat model. Cytotoxicity assay and ADME prediction also supported that 3i is an excellent lead for further exploration of amide-based XO inhibitors.

Amide-based xanthine oxidase inhibitors bearing an N-(1-alkyl-3-cyano-1H-indol-5-yl) moiety: Design, synthesis and structure-activity relationship investigation

Our previous work identified a promising isonicotinamide based xanthine oxidase (XO) inhibitor, N-(3-cyano-4-((2-cyanobenzyl)oxy)phenyl)isonicotinamide (1), and concluded that amide is an effective linker in exploring the XO inhibitor chemical space that is completely different from the five-membered ring framework of febuxostat and topiroxostat. Indole, an endogenous bioactive substance and a popular drug construction fragment, was involved in the structural optimization campaign of the present effort. After the installation of some functional groups, N-(1-alkyl-3-cyano-1H-indol-5-yl) was generated and employed to mend the missing H-bond interaction between the 3′-cyano of 1 and Asn768 residue of XO by shortening their distance. In this context, eight kinds of heterocyclic aromatic amide chemotypes were rationally designed and synthesized to investigate the structure-activity relationship (SAR) of amide-based XO inhibitors. The optimized compound a6 (IC50 = 0.018 μM) exhibits 17.2-fold improved potency than the initial compound 1 (IC50 = 0.31 μM). Its potency is comparable to that of topiroxostat (IC50 = 0.013 μM). Molecular docking and molecular dynamics studies proved the existence of the stable H-bond between the cyano group and the Asn768 residue. Moreover, oral administration of a6 (11.8 mg/kg) could effectively reduce serum uric acid levels in an acute hyperuricemia rat model. Liver microsomal stability assay illustrated that compound a6 possesses well metabolic stability in rat liver microsomes. However, the in vivo potency of a6 was much lower than that of topiroxostat, which may be explained by the poor absorption found in the parallel artificial membrane permeability assay (PAMPA). In addition, 6a has non-cytotoxicity against normal cell lines MCF10A and 16HBE. Taken together, this work culminated in the identification of compound 6a as an excellent lead for further exploration of amide-based XO inhibitors.

N-indole-1,6-dihydropyrimidine-4-carboxamide derivative as well as preparation method and application thereof

The invention relates to an N-indole-1,6-dihydropyrimidine-4-carboxamide derivative as well as a preparation method and application thereof, belonging to the technical field of medicines. According to the invention, amide is innovatively applied as a connecting fragment in the design of a non-purine xanthine oxidase inhibitor, and the N-indole-1,6-dihydropyrimidine-4-carboxamide derivative is synthesized. An in-vitro xanthine oxidase inhibitory activity test is carried out on the designed derivative by adopting an ultraviolet spectrophotometric method, and the prepared derivative shows obvious xanthine oxidase inhibitory activity. In an acute hyperuricemia rat model test, the derivative can significantly reduce the uric acid level of serum, and thus has good in-depth research value as the novel xanthine oxidase inhibitor.

Design and Synthesis of Pyrano[3,2-b]indolones Showing Antimycobacterial Activity

Latent Mycobacterium tuberculosis infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2-b]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their in vitro activity against M. tuberculosis strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively. Compound 10a exhibited good activity with MIC99 values of 0.3 and 0.4 μg/mL against H37Rv and SS18b, respectively, as well as low toxicity, acceptable intracellular activity, and satisfactory metabolic stability and was selected as the lead compound for further studies. An analysis of 10a-resistant M. bovis mutants disclosed a cross-resistance with pretomanid and altered relative amounts of different forms of cofactor F420 in these strains. Complementation experiments showed that F420-dependent glucose-6-phosphate dehydrogenase and the synthesis of mature F420 were important for 10a activity. Overall these studies revealed 10a to be a prodrug that is activated by an unknown F420-dependent enzyme in mycobacteria.

Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.

Molecular iodine mediated oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups into aldehydes

The oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups is achieved by employing molecular iodine as a mild oxidizing agent under ambient conditions in the presence of a mild base. The important reaction of C3 formylation of free NH and substituted indoles containing various substituents is accomplished from the corresponding Mannich bases. This methodology can also be extended for the synthesis of aryl and other heteroaryl aldehydes and ketones. Furthermore, the usefulness of the method is successfully demonstrated on a gram scale.

SMALL MOLECULE DIRECT INHIBITORS OF KEAP1-NRF2 PROTEIN-PROTEIN INTERACTION

This patent document diclsoes novel compounds and methods of preventing or treating diseases or conditions related to Keapl-Nrf2 interaction activity by use of the novel compounds. As direct inhibitors of Keapl-Nrf2 interaction, the compounds disclosed herein are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential dmg candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, Parkinson's, and inflammatory bowel disease including ulcerative colitis.