16732-57-3

Usage

Uses

Used in Pharmaceutical Synthesis:
Ethyl 5-nitroindole-2-carboxylate is used as a reagent for the synthesis of indol-2-yl ethanones, which are novel indoleamine 2,3-dioxygenase (IDO) inhibitors. These inhibitors play a significant role in the development of treatments for various diseases, including cancer and neurodegenerative disorders, by modulating the IDO enzyme.
Used in the Synthesis of Delavirdine:
Ethyl 5-nitroindole-2-carboxylate is also a useful synthetic intermediate in the synthesis of Delavirdine, a bisheteroarylpiperazine (BHAP) reverse transcriptase inhibitor. Delavirdine is an antiretroviral medication used to treat HIV-1 infection, and its synthesis involves the use of Ethyl 5-nitroindole-2-carboxylate as a key component.

InChI:InChI=1/C11H10N2O4/c1-2-17-11(14)10-6-7-5-8(13(15)16)3-4-9(7)12-10/h3-6,12H,2H2,1H3

Upstream product

• 100-16-3 4-nitrophenylhydrazone 
• 2999-46-4 Ethyl isocyanoacetate 
• 84459-32-5 2-bromo-5-nitrobenzaldehyde 
• 617-35-6 2-oxo-propionic acid ethyl ester 
• 636-99-7 4-nitrophenylhydrazine hydrochloride 
• 100-01-6 4-nitro-aniline 
• 63190-15-8 ethyl (Z)-2-(2-(4-nitrophenyl)hydrazineylidene)propanoate 
• 73647-04-8 ethyl 2-[2-(4-nitrophenyl)hydrazinylidene]propanoate 

Downstream Products

• 74944-39-1 Ethyl 3-(α,o-dichlorobenzyl)-5-nitroindole-2-carboxylate 
• 71086-99-2 ethyl 5-amino-1H-indole-2-carboxylate 
• 1221418-56-9 C₁₇H₁₁BrN₄O₄ 
• 136817-55-5 delavirdine 

Relevant academic research and scientific papers

Acetic anhydride to the rescue: Facile access to privileged 1,2,3,4-tetrahydropyrazino[1,2-a]indole core via the Castagnoli-Cushman reaction

Indole-fused cyclic anhydrides earlier deemed unreactive in the Castagnoli-Cushman reaction with imines have been rendered valid participant in this process. The new reaction format involves the use of respective indole-based dicarboxylic acids and in sit

Design, synthesis and biological evaluation of methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold: Novel potential CDK9 inhibitors

In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 inhibitory activity and anticancer activity. Biological activity results demonstrated that most of these derivatives possessed good inhibitory on the kinase activity of CDK9 such as blocking its phosphorylation function and inhibiting HIV-1 transcription. Compound 12i was found to be the most potent CDK9 inhibitor and exhibited excellent anticancer activity against HepG2, A375, MCF-7, and A549, but low toxic on normal cells including HaCaT and MCF-10A. Further studies revealed that as a result of CDK9 inhibition and subsequent inhibition of phosphorylation at Serine 2 of the RNAPII CTD, the representative compound 12i dose-dependently increased cleaved PARP level, exerting its antiproliferative effect through induction of apoptosis in cancer cells. Finally, the molecular docking analysis implied that 12i had a good binding affinity with CDK9. In summary, 12i is a potent CDK9 inhibitor and can be considered as a good lead-candidate for developing potential anticancer drugs.

Synthesis, structure–activity relationship studies and biological evaluation of novel 2,5-disubstituted indole derivatives as anticancer agents

Three novel series of 2,5-disubstituted indole derivatives were synthesized and evaluated in vitro for their antiproliferative activity against human cancer cells and HIV-1 inhibition activity used as a readout of cellular activity. Most compounds were found to have potent anticancer activity. In particular, 2c and 3b which showed effectively to repress HIV-1 transcription had a pan antiproliferative activity in cervical cancer cells (HeLa), breast cancer cells (MCF-7), liver cancer cells (HepG2), and lung cancer cells (H460 and A549). While 3b exhibited high sensitivity to A549 cells with the IC50 value 0.48?±?0.15?μm, 2c showed high selectivity toward HepG2 cells with the IC50 value 13.21?±?0.30?μm. With respect to the cellular mechanism of action, HepG2 cells treated with 2c and A549 cells treated with 3b for 24?h were studied by annexin V/PI staining and Western blot analysis, and results revealed that 2c and 3b may induce cancer cells apoptosis through inhibiting the phosphorylation at Ser2 of RNAPII CTD which can be phosphorylated by cyclin-dependent kinase 9. These studies indicated that 2c and 3b may develop as potent lead compounds in the therapy of cancer. However, determining their roles in preventing HIV-1 still requires further intensive study.

Synthesis, SAR study, and bioactivity evaluation of a series of Quinoline-Indole-Schiff base derivatives: Compound 10E as a new Nur77 exporter and autophagic death inducer

We previously reported 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole- 2-carbohydrazide derivatives as new Nur77 modulators. In this study, we explored whether the 8-methoxy-2-methylquinoline moiety and bicyclic aromatic rings at the N’-methylene position were critical for their antitumor activity against hepatocellular carcinoma (HCC). For this purpose, a small library of 5-substituted 1H-indole-2-carbohydrazide derivatives was designed and synthesized. We found that the 8-methoxy-2-methylquinoline moiety was a fundamental structure for its biological function, while the introduction of the bicyclic aromatic ring into the N’-methylene greatly improved its anti-tumor effect. We found that the representative compound 10E had a high affinity to Nur77. The KD values were in the low micromolar (2.25–4.10 μM), which were coincident with its IC50 values against the tumor cell lines (IC50 3.78 μM). Compound 10E could induce autophagic cell death of liver cancer cells by targeting Nur77 to mitochondria while knocking down Nur77 greatly impaired anti-tumor effect. These findings provide an insight into the structure–activity relation of Quinoline-Indole-Schiff base derivatives and further demonstrate that antitumor agents targeting Nur77 may be considered as a promising strategy for HCC therapy.

Design, synthesis, and biological evaluation of 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole-2-carbohydrazide derivatives as novel Nur77 modulators

Nur77 is a potential target for the treatment of cancer such as HCC. Herein, we detailed the discovery of a novel series of 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole-2-carbohydrazide derivatives as potential Nur77 modulators. The studies of antiproliferative activity and Nur77-binding affinity of target compounds resulted in the discovery of a lead candidate (10g), which was a good Nur77 binder (KD = 3.58 ± 0.16 μM) with a broad-spectrum antiproliferative activity against all tested hepatoma cells (IC50 2.0 μM) and was low toxic to normal LO2 cells. 10g could up-regulate Nur77 expression and mediate sub-cellular localization of Nur77 to induce apoptosis in hepatocellular carcinoma cell lines, which relied on 10g inducing Nur77-dependent autophagy and endoplasmic reticulum stress as the upstream of apoptosis. Moreover, the in vivo assays verified that 10g significantly inhibited xenograft tumor growth. These results indicate that 10g has the potential to be developed as a novel Nur77-targeting anti-hepatoma drug.

Pyrimidine indole Nur77 receptor regulating agent, preparation method and application thereof

The invention provides a pyrimidine indole Nur77 receptor regulating agent, a preparation method and an application thereof and relates to pyrimidine indole derivatives. The invention provides a pyrimidine indole derivative with a novel structure, a pharm

5 - (Substituted carbonylamino-) - 1H - indole -2 - hydrazine derivative and its preparation method and application

The invention provides 5-(substituted carbonylamino)-1H-indole-2-carbohydrazide derivatives as well as a preparation method and an application thereof. The preparation method comprises steps as follows: 1), preparing an intermediate ethyl pyruvate p-nitrobenzoylhydrazone; 2), preparing an intermediate 5-nitroindole-2-carboxylic ethyl ester; 3), preparing an intermediate 5-amino-1H-indole-2-carboxylic ethyl ester; 4), preparing an intermediate 5-(substituted carbonylamino)-1H-indole-2-carboxylic ethyl ester; 5), preparing an intermediate 5-(substituted carbonylamino)-1H-indole-2-carbohydrazide; 6), preparing N'-substituted methylene-5-(substituted carbonylamino)-1H-indole-2-carbohydrazide derivatives. The N'-substituted methylene-5-(substituted carbonylamino)-1H-indole-2-carbohydrazide derivatives can be applied to preparation of drugs for preventing or treating CDK9 (cyclin-dependent kinase 9) receptor related diseases. The reaction cost is low, the yield is high, the reaction process is simple and easy to control, and the derivatives have antitumor activity.

1 H - indole -2 - hydrazine derivative and its preparation and use

The invention provides a 1H-indol-2-carbohydrazide derivative as well as a preparation method and the use of the derivative. The preparation method comprises the following steps: 1) synthesizing an intermediate ethyl pyruvate p-nitrobenzene hydrazine; 2) preparing an intermediate 5-nitroindole-2-ethyl carboxylate; 3) preparing an intermediate 5-amino-1H-indol-2-ethyl carboxylate; 4) preparing 5-(4-(pyridyl-3)pyrimidyl-2-amino)-1H-indol-2-ethyl carboxylate; 5) preparing 5-(4-(pyridyl-3)pyrimidyl-2)amino)-1H-indol-2-carbohydrazide; 6) preparing the N'-substituted methylene-5-((4-(pyridyl-3)pyrimidyl-2)amino)-1H-indol-2-carbohydrazide derivative. The 1H-indol-2-carbohydrazide derivative can be applied to preparation of medicines for preventing or treating related CDK9 receptor related diseases.

N-substituted-5-((4-substituted pyrimidine-2-yl)amino)indole derivative as well as preparation method and purpose thereof

The invention discloses an N-substituted-5-((4-substituted pyrimidine-2-yl)amino)indole derivative as well as a preparation method and a purpose thereof, and relates to malignant tumor drugs. A structure of the N-substituted-5-((4-substituted pyrimidine-2

Oligomer modified diaromatic substituted compounds

Disclosed are compounds comprising diaromatic substituted compound residues, namely the anti-viral (anti-HIV) drug delavirdine, covalently attached via a linkage to water-soluble, non-peptidic oligomers, specifically to poly(ethylene glycol) (PEG) oligome