7147-14-0

Usage

Uses

Used in Pharmaceutical Industry:
3-Cyano-5-nitroindole is used as a building block for the synthesis of various pharmaceutical compounds due to its versatile reactivity and ability to serve as a key intermediate in organic reactions. Its potential biological activities, such as anti-inflammatory, anti-proliferative, and anticancer properties, make it a valuable target for the development of new drugs.
Used in Agrochemical Industry:
3-Cyano-5-nitroindole is also used as a building block in the synthesis of agrochemical compounds, contributing to the development of new pesticides and other agricultural chemicals. Its versatile reactivity and potential biological activities play a crucial role in enhancing the effectiveness and selectivity of these compounds.
Used in Medicinal Chemistry Research:
3-Cyano-5-nitroindole is employed as a valuable target in medicinal chemistry research for the development of new drugs. Its anti-inflammatory, anti-proliferative, and anticancer properties make it a promising candidate for the treatment of various diseases and conditions.
Used in Drug Discovery:
3-Cyano-5-nitroindole is utilized in drug discovery processes to identify and develop new therapeutic agents with potential applications in various medical fields. Its unique chemical structure and biological activities provide a solid foundation for the design and synthesis of novel drug candidates.

InChI:InChI=1/C9H5N3O2/c10-4-6-5-11-9-2-1-7(12(13)14)3-8(6)9/h1-3,5,11H

Upstream product

• 6625-96-3 5-nitro-1H-indole-3-carbaldehyde 
• 6146-52-7 5-nitroindole 
• 110-18-9 N,N,N,N,-tetramethylethylenediamine 
• 928664-98-6 4-isoxazoleboronic acid pinacol ester 
• 159768-57-7 5-amino-1H-indole-3-carbonitrile 
• 140-29-4 phenylacetonitrile 
• 1058740-61-6 5-nitro-1H-indole-3-carbonyl chloride 
• 6958-37-8 5-nitro-1H-indole-3-carboxylic acid 
• 128200-32-8 5-nitro-1H-indole-3-carboxamide 

Downstream Products

• 159768-57-7 5-amino-1H-indole-3-carbonitrile 

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.

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.

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.

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-(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-(indol-5-yl) aromatic heterocyclic amide compound and preparation method and application thereof

The invention belongs to the field of medicines, and relates to an N-(indole-5-yl) aromatic heterocyclic amide compound and a preparation method and application thereof. The structural general formula of the N-(indol-5-yl) aromatic heterocyclic amide compound is shown in the specification. A pharmaceutical composition comprises the N-(indol-5-yl) aromatic heterocyclic amide compound, a pharmaceutically acceptable salt, a hydrate or a solvate of the N-(indol-5-yl) aromatic heterocyclic amide compound and a pharmaceutically acceptable carrier of the N-(indol-5-yl) aromatic heterocyclic amide compound. The invention further discloses application of the N-(indol-5-yl) aromatic heterocyclic 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-indolyl imidazole formamide compound and preparation method and application thereof

The invention belongs to the field of medicines, and relates to an N-indolyl imidazole formamide compound and a preparation method and application thereof. The structural general formula of the compound is shown in the specification. A pharmaceutical composition comprises the N-indolyl imidazole carboxamide compound, pharmaceutically acceptable salt, hydrate or solvate of the N-indolyl imidazole carboxamide compound and a pharmaceutically acceptable carrier of the N-indolyl imidazole carboxamide compound. The invention also discloses the application of the N-indolyl imidazole formamide compound or the pharmaceutically acceptable salt, hydrate or solvate thereof or the pharmaceutical composition in the 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 is simple and feasible, relatively high in yield and easy for large-scale production.

Chemoselective Cu-catalyzed synthesis of diverseN-arylindole carboxamides, β-oxo amides andN-arylindole-3-carbonitriles using diaryliodonium salts

Chemoselective copper-catalyzed synthesis of diverseN-arylindole-3-carboxamides, β-oxo amides andN-arylindole-3-carbonitriles from readily accessible indole-3-carbonitriles, α-cyano ketones and diaryliodonium salts has been developed. DiverseN-arylindole-3-carboxamides and β-oxo amides were successfully achieved in high yields under copper-catalyzed neutral reaction conditions, and the addition of an organic base (DIPEA) resulted in a completely different selectivity pattern to produceN-arylindole-3-carbonitriles. Moreover, the importance of the developed methodology was realized by the synthesis of indoloquinolones andN-((1H-indol-3-yl)methyl)aniline and by a single-step gram-scale synthesis of the naturally occurring cephalandole A analogue.

Efficient construction of diverse 3-cyanoindoles under novel tandem catalysis

A novel and rapid construction of 3-cyanoindoles by palladium-catalyzed tandem reactions has been developed. "N-H"free unprotected, N-alkyl and N-aryl 3-cyanoindoles are obtained with good to excellent yields. The usefulness of this synthetic approach is further demonstrated by the successful synthesis of practical compounds such as the therapeutic estrogen receptor ligand A precursor. Mechanism study shows that the tandem catalysis exploits a Suzuki cross-coupling with subsequent base-induced isoxazole fragmentation, followed by the aldimine condensation.

1-substituted-3-substituted-5-substituted amide-1H-indole compounds as well as preparation method and application thereof

The invention belongs to the technical field of medicines, and particularly relates to 1-substituted-3-substituted-5-substitutedamide-1H-indole compounds as well as a preparation method and application thereof. The structural general formula I of the compounds is specifically shown in the specification. Pharmacological research shows that the compounds show a good effect in an in-vitro xanthine oxidase inhibitory activity test, and are free of obvious toxic and side effect. The preparation method of the 1-substituted-3-substituted-5-substituted amide-1H-indole compounds provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.