71086-99-2

Usage

Uses

Used in Pharmaceutical Synthesis:
5-AMINO-2-INDOLE CARBOXYLIC ACID is used as a key intermediate in the synthesis of various pharmaceuticals and organic compounds. Its indole ring structure and functional groups make it a versatile building block for the development of new drugs and molecules with therapeutic potential.
Used in Drug Development:
5-AMINO-2-INDOLE CARBOXYLIC ACID is used as a starting material for drug development due to its potential biological activities. It has been investigated for its potential as an anticancer agent, and further research is being conducted to explore its therapeutic applications in treating various types of cancer.
Used in Medicinal Chemistry:
5-AMINO-2-INDOLE CARBOXYLIC ACID is used as a research compound in medicinal chemistry. Its unique properties and indole ring structure make it an interesting candidate for the design and synthesis of novel molecules with potential therapeutic effects. Researchers are exploring its interactions with biological targets and its potential to modulate various signaling pathways.

InChI:InChI=1/C11H12N2O2/c1-2-15-11(14)10-6-7-5-8(12)3-4-9(7)13-10/h3-6,13H,2,12H2,1H3

Upstream product

• 409315-76-0 5-isocyanato-indole-2-carboxylic acid ethyl ester 
• 16732-57-3 5-nitro-indole-2-carboxylic acid ethyl ester 
• 1227862-58-9 5'-amino-4-phenyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-ol 
• 63190-15-8 ethyl (Z)-2-(2-(4-nitrophenyl)hydrazineylidene)propanoate 
• 617-35-6 2-oxo-propionic acid ethyl ester 
• 73647-04-8 ethyl 2-[2-(4-nitrophenyl)hydrazinylidene]propanoate 
• 100-16-3 4-nitrophenylhydrazone 
• 138731-14-3 1H-indole-2,5-dicarboxylic acid 2-ethyl ester 

Downstream Products

• 152213-40-6 5-amino-1H-indole-2-carboxylic acid 
• 284662-75-5 5-(4-tert-butoxycarbonylamino-benzoylamino)-1H-indole-2-carboxylic acid ethyl ester 
• 294174-59-7 5-{4-[bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carboxylic acid ethyl ester 
• 138730-81-1 5-[(tert-Butyloxycarbonyl)amino]indole-2-carboxylic Acid 
• 104713-39-5 U-71,185 
• 101222-80-4 U-71,184 
• 108859-64-9 1H-Indole-2-carboxylic acid [2-((S)-5-benzyloxy-1-hydroxymethyl-8-methyl-1,6-dihydro-2H-pyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl]-amide 
• 108833-15-4 Methanesulfonic acid (S)-5-benzyloxy-3-{5-[(1H-indole-2-carbonyl)-amino]-1H-indole-2-carbonyl}-8-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-e]indol-1-ylmethyl ester 
• 383674-95-1 ethyl 5-[[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]amino]-1H-indole-2-carboxylate 
• 179556-52-6 1-benzyl-4-(N-methyl-N-(3-methoxymethyl-2-pyridinyl)amino)piperidine 
• 881742-40-1 5-(4-tert-butyl-phenylsulfonylamino )-1H-indole-2-carboxylic acid ethyl ester 
• 1228694-10-7 methyl (S)-5-(benzyloxy)-1-(chloromethyl)-3-(5-acetylaminoindole-2-carbonyl)-1,2-dihydropyrrolo[3,2-e]indole-2-carboxylate 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel FXIa inhibitors with 2-phenyl-1H-imidazole-5-carboxamide moiety as P1 fragment

Factor XIa, as a blood coagulation enzyme, amplifies the generation of the last enzyme thrombin in the blood coagulation cascade. It was proved that direct inhibition of factor XIa could reduce pathologic thrombus formation without an enhanced risk of bleeding. WSJ-557, a nonpurine imidazole-based xanthine oxidase inhibitor in our previous reports, could delay blood coagulation during its animal experiments, which prompted us to investigate its action mechanism. Subsequently, during the exploration of the action mechanism, it was found that WSJ-557 exhibited weak in vitro factor XIa binding affinity. Under the guide of molecular modeling, we adopted molecular hybridization strategy to develop novel factor XIa inhibitors with WSJ-557 as an initial compound. This led to the identification of the most potent compound 44g with a Ki value of 0.009 μM, which was close to that of BMS-724296 (Ki = 0.0015 μM). Additionally, serine protease selectivity study indicated that compound 44g display a desired selectivity, more 400-fold than those of thrombin, factor VIIa and factor Xa in coagulation cascade. Moreover, enzyme kinetics studies suggested that the representative compound 44g acted as a competitive-type inhibitor for FXIa, and molecular modeling revealed that it could tightly bind to the S1, S1′ and S2′ pockets of factor XIa. Furthermore, in vivo efficacy in the rabbit arteriovenous shunt model suggested that compound 44g demonstrated dose-dependent antithrombotic efficacy. Therefore, these results supported that compound 44g could be a potential and efficacious agent for the treatment of thrombotic diseases.

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.

INHIBITORS OF HSP70 PROTEINS

Provided are compounds useful for selectively inhibiting HSP70 isoforms. Also provided are methods of inhibiting HSP70 proteins and methods of treating a disease characterized by overexpression of a HSP70, such as cancer. In particular embodiments, the disclosed compounds may be used as potent inhibitors for HSPA5 and may display greater than 20-fold selectivity over other HSP70 isoforms.

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.

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

An optimised series of substituted N-phenylpyrrolamides as DNA gyrase B inhibitors

ATP competitive inhibitors of DNA gyrase and topoisomerase IV have great therapeutic potential, but none of the described synthetic compounds has so far reached the market. To optimise the activities and physicochemical properties of our previously reported N-phenylpyrrolamide inhibitors, we have synthesized an improved, chemically variegated selection of compounds and evaluated them against DNA gyrase and topoisomerase IV enzymes, and against selected Gram-positive and Gram-negative bacteria. The most potent compound displayed IC50 values of 6.9 nM against Escherichia coli DNA gyrase and 960 nM against Staphylococcus aureus topoisomerase IV. Several compounds displayed minimum inhibitory concentrations (MICs) against Gram-positive strains in the 1–50 μM range, one of which inhibited the growth of Enterococcus faecalis, Enterococcus faecium, S. aureus and Streptococcus pyogenes with MIC values of 1.56 μM, 1.56 μM, 0.78 μM and 0.72 μM, respectively. This compound has been investigated further on methicillin-resistant S. aureus (MRSA) and on ciprofloxacin non-susceptible and extremely drug resistant strain of S. aureus (MRSA VISA). It exhibited the MIC value of 2.5 μM on both strains, and MIC value of 32 μM against MRSA in the presence of inactivated human blood serum. Further studies are needed to confirm its mode of action.

Synthesis method of indole-2-carboxylic acid and derivative thereof

The invention relates to a synthesis method of indole-2-carboxylic acid and a derivative thereof, belonging to the field of organic synthesis. In the synthesis method, the indole-2-carboxylic acid isprepared through two steps of reaction with phenylhydrazine hydrochloride and ethyl pyruvate as raw materials and sulfuric acid as a catalyst. The synthesis method has a short process and uses fewer raw materials, the total yield of indole-2-carboxylic acid reaches 70% or above. The method can synthesize both indole-2-carboxylic acid and the derivative thereof, thereby being suitable for industrial production.

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

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.