19727-83-4

Basic information

• Product Name: 6-Nitroindoline
• Synonyms: 2,3-DIHYDRO-6-NITRO-(1H)-INDOLE;6-NITROINDOLINE;6-NITRO-2,3-DIHYDROINDOLE;6-NITRO-2,3-DIHYDRO-1H-INDOLE;6-NITRO-2,3-DIHYDRO-1H-INDOLE HYDROCHLORIDE;6-nitro-indolin;6-Nitroindzole;6-NITROINDOLINE, 98+%
• CAS NO: 19727-83-4
• Molecular Formula: C₈H₈N₂O₂
• Molecular Weight: 164.16
• EINECS: 243-257-6
• Product Categories: Indoles and derivatives;Building Blocks;Heterocyclic Building Blocks;Indoles;Building Blocks;C7 to C9;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 19727-83-4.mol

Chemical Properties

• Melting Point: 67-69 °C(lit.)
• Boiling Point: 291.62°C (rough estimate)
• Flash Point: 139.3 °C
• Appearance: Orange or red/Crystalline Powder or Crystals
• Density: 1.2739 (rough estimate)
• Vapor Pressure: 0.000762mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 3.39±0.20(Predicted)
• BRN: 156434
• CAS DataBase Reference: 6-Nitroindoline(CAS DataBase Reference)
• NIST Chemistry Reference: 6-Nitroindoline(19727-83-4)
• EPA Substance Registry System: 6-Nitroindoline(19727-83-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• RTECS: NM1950000
• Hazardous Substances Data: 19727-83-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
6-Nitroindoline is used as a reactant for the preparation of 2-[(2,3-Dihydro-1H-indol-1-yl)methyl]melatonin analogs, which are novel MT2-selective melatonin receptor antagonists. These antagonists have potential applications in the treatment of various disorders related to melatonin receptor dysregulation.
Used in Anticancer Applications:
In the field of oncology, 6-Nitroindoline is utilized as a reactant for the synthesis of isoindigo and azaisoindigo glycosides. These compounds exhibit anticancer properties and are being investigated for their potential use in cancer treatment.
Used in Pain Management:
6-Nitroindoline is also used as a reactant for the preparation of arylfurancarboxamides. These compounds possess Nav1.8 voltage-gated sodium channel blocking and analgesic activities, making them potential candidates for the development of pain management therapies.
Used in Cardiovascular Applications:
In the cardiovascular field, 6-Nitroindoline is employed as a reactant for the preparation of bicyclic benzamides. These compounds act as 5-HT1 receptor agonists, which may have potential applications in the treatment of various cardiovascular conditions.
Used in Antiarrhythmic Drug Development:
6-Nitroindoline is used as a reactant for the preparation of antiarrhythmic benzopyrans. These compounds have the potential to be developed into antiarrhythmic drugs, which can help regulate abnormal heart rhythms.
Used in Neurological Applications:
Lastly, 6-Nitroindoline is used as a reactant for the preparation of 5-HT2C/2B receptor antagonists. These antagonists may have potential applications in the treatment of neurological disorders associated with the dysregulation of serotonin receptors.

InChI:InChI=1/C8H8N2O2/c11-10(12)7-2-1-6-3-4-9-8(6)5-7/h1-2,5,9H,3-4H2

Upstream product

• 496-15-1 1-indoline 
• 7664-93-9 sulfuric acid 
• 7697-37-2 nitric acid 
• 4769-96-4 6-nitroindole 

Downstream Products

• 79063-65-3 C₂₉H₂₆N₂O₇ 
• 79063-63-1 C₂₉H₂₆N₂O₇ 
• 127973-91-5 methyl 3-methoxy-4-<(6-nitro-2,3-dihydroindol-1-yl)methyl>benzoate 
• 1025939-10-9 {(E)-(S)-4-(6-Nitro-2,3-dihydro-indol-1-yl)-4-oxo-1-[2-(trityl-carbamoyl)-ethyl]-but-2-enyl}-carbamic acid tert-butyl ester 
• 120627-46-5 N-benzyl-6-nitroindole 
• 99459-48-0 1-methyl-6-nitro-indole 
• 403600-05-5 (R,S)-ethyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3-(quinolin-3-yl)propanoate 
• 403600-04-4 (R,S)-ethyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3-(naphthalen-2-yl)propanoate 
• 229636-73-1 (R,S)-ethyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3-(pyridin-3-yl)propanoate 
• 403600-26-0 (R,S)-ethyl 3-{3-[6-(3-phenylureido)indolin-1-yl]-3-oxopropanoylamino}-3-(pyridin-3-yl)propanoate 
• 403600-03-3 (R,S)-methyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3-phenylpropanoate 
• 403600-01-1 (R,S)-ethyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxo-propanoylamino}propanoate 
• 403600-02-2 (R,S)-ethyl 3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3-methylpropanoate 

Relevant articles and documents

Discovery of N-indanyl benzamides as potent RORγt inverse agonists

The retinoic acid receptor-related orphan receptor-gamma-t (RORγt) is a promising therapeutic target for treatment of Th17 cell-mediated autoimmune diseases. Based on a scaffold hopping/conformational restriction strategy, a series of N-indanyl benzamides as novel RORγt inverse agonists was discovered. Exploration of structure-activity relationship on the piperazine ring, benzoyl moiety and cyclopentyl moiety of N-indanyl benzamides 2a and 2d led to identification of potent RORγt inverse agonists. Compound 5c with (S)-enantiomer was found having an IC50 of 153.7 nM in Fluorescence Resonance Energy Transfer (FRET) assay, and an IC50 of 47.1 nM in mouse Th17 cell differentiation assay, which represents a promising starting point for developing potent small molecule RORγt inverse agonists. Binding modes of the two enantiomers 5c and 5d in RORγt ligand binding domain were also discussed.

Palladium-Catalyzed Direct and Specific C-7 Acylation of Indolines with 1,2-Diketones

The indole scaffold is a ubiquitous and useful substructure, and extensive investigations have been conducted to construct the indole framework and/or realize indole modification. Nevertheless, the direct selective functionalization on the benzenoid core must overcome the high activity of the C-3 position and still remains highly challenging. Herein, a palladium-catalyzed direct and specific C-7 acylation of indolines in the presence of an easily removed directing group was developed. This strategy usually is considered as a practical strategy for the preparation of acylated indoles because indoline can be easily converted to indole under oxidation conditions. In particular, our strategy greatly improved the alkacylation yield of indolines for which only an unsatisfactory yield could be achieved in the previous studies. Furthermore, the reaction can be scaled up to gram level in the standard reaction conditions with a much lower palladium loading (1 mol %).

The Relation Between Position and Chemical Composition of Bis-Indole Substituents Determines Their Interactions with G-Quadruplex DNA

G-quadruplex (G4) DNA structures are linked to fundamental biological processes and human diseases, which has triggered the development of compounds that affect these DNA structures. However, more knowledge is needed about how small molecules interact with G4 DNA structures. This study describes the development of a new class of bis-indoles (3,3-diindolyl-methyl derivatives) and detailed studies of how they interact with G4 DNA using orthogonal assays, biophysical techniques, and computational studies. This revealed compounds that strongly bind and stabilize G4 DNA structures, and detailed binding interactions which for example, show that charge variance can play a key role in G4 DNA binding. Furthermore, the structure–activity relationships generated opened the possibilities to replace or introduce new substituents on the core structure, which is of key importance to optimize compound properties or introduce probes to further expand the possibilities of these compounds as tailored research tools to study G4 biology.

Flexible Versus Rigid G-Quadruplex DNA Ligands: Synthesis of Two Series of Bis-indole Derivatives and Comparison of Their Interactions with G-Quadruplex DNA

Small molecules that target G-quadruplex (G4) DNA structures are not only valuable to study G4 biology but also for their potential as therapeutics. This work centers around how different design features of small molecules can affect the interactions with G4 DNA structures, exemplified by the development of synthetic methods to bis-indole scaffolds. Our synthesized series of bis-indole scaffolds are structurally very similar but differ greatly in the flexibility of their core structures. The flexibility of the molecules proved to be an advantage compared to locking the compounds in the presumed bioactive G4 conformation. The flexible derivatives demonstrated similar or even improved G4 binding and stabilization in several orthogonal assays even though their entropic penalty of binding is higher. In addition, molecular dynamics simulations with the c-MYC G4 structure showed that the flexible compounds adapt better to the surrounding. This was reflected by an increased number of both stacking and polar interactions with both the residues in the G4 DNA structure and the DNA residues just upstream of the G4 structure.

Nucleophilic substitution reaction in indole chemistry: 1-methoxy-6-nitroindole-3-carbaldehyde as a versatile building block for 2,3,6-trisubstituted indoles

1-Methoxy-6-nitroindole-3-carbaldehyde is proved to be a versatile electrophile and reacts regioselectively at the 2-position with various types of nucleophiles providing 2,3,6-trisubstituted indole derivatives. The reaction is applicable for the preparation of a novel pyrimido[1,2-a]indole derivative.

New antiproliferative benzoindolinothiazepines derivatives

New benzoindolinothiazepines containing a piperazine moiety are described as potent antiproliferative agents against PC3 human prostatic cell lines. This activity could be explained by an accumulation of cells in G1 phase.

5H-[1,2,5]selenadiazolo[3,4-f]indole as a masked form of 5,6-diaminoindole

6-Nitroindoline (9) was converted into 1-acetyl-5,6-aminoindoline (12) which was then transformed via selenadiazoles (13-15) to the title selenadiazoloindole (4) by two alternative 3-step synthetic sequences in 38-42% overall yield from 12. The unstable 5,6-diaminoindole (16) was then obtained by reductive deselenation of 4. Fully assigned 1H, 13C and 77Se NMR spectral data for the title indole (4) and 77Se NMR spectral data for the intermediate selenadiazoles (13-15) are presented.

Synthesis of 1-benzyl-8,9-dihydroimidazo[4,5-c]pyrrolo[3,2-g]quinolin-4(5H) -one via palladium-catalyzed intramolecular arylation

The synthesis of a novel tetracyclic structure, 8,9-dihydroimidazo[4,5-c] pyrrolo[3,2-g]quinolin-4(5H)-one, has been achieved by a convergent pathway. Coupling of the weakly nucleophilic hindered aromatic amine with 1-benzylimidazole-4-carboxylic acid, 7, afforded the corresponding amide 9 using a DCP/DMF complex; subsequent Heck-type arylation leading to desired tetracyclic molecule imidazo[4,5-c]-pyrrolo[3,2-g]quinolin-4(5H)-one.

Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 7b. Their related synthesis was also reported.

Nucleophilic substitution reactions of 1-methoxy-6-nitroindole-3-carbaldehyde 1

1-Methoxy-6-nitroindole-3-carbaldehyde is proved to be a versatile substrate for the nucleophilic substitution reactions providing 2,3,6-trisubstituted indole derivatives. Preparation of a novel pyrimido[1,2-a]indole derivative is also reported.