404827-77-6

Usage

Uses

Used in Pharmaceutical Research and Development:
6-BROMO-1H-INDAZOL-3-YLAMINE is used as a key intermediate in the synthesis of pharmaceuticals for the treatment of a range of diseases, including cancer, neurological disorders, and infectious diseases. Its unique chemical properties and structure contribute to the development of novel therapeutic agents with potential therapeutic effects.
Used in Drug Synthesis:
In the pharmaceutical industry, 6-BROMO-1H-INDAZOL-3-YLAMINE is utilized as a building block for creating bioactive molecules that can target specific biological pathways. Its role in drug synthesis is crucial for the advancement of new medicines with improved efficacy and safety profiles.
Used in Medicinal Chemistry:
6-BROMO-1H-INDAZOL-3-YLAMINE is employed as a valuable tool in medicinal chemistry for exploring its interactions with various biological targets. This helps in understanding its potential therapeutic effects and optimizing its properties for specific medical applications.

InChI:InChI=1/C7H6BrN3/c8-4-1-2-5-6(3-4)10-11-7(5)9/h1-3H,(H3,9,10,11)

Upstream product

• 105942-08-3 4-bromo-6-fluorobenzonitrile 

Downstream Products

• 599191-53-4 N-[6-bromo-1H-indazol-3-yl]butanamide 
• 627859-39-6 N'-(6-bromo-1H-indazol-3-yl)-N,N-dimethylimidoformamide 
• 1279846-99-9 6-bromo-1-[(thiophen-3-yl)carbonyl]-3-[(thiophen-3-yl)carbonylamino]indazole 
• 1227909-36-5 N-acetyl-N-(1-acetyl-6-bromo-1H-indazol-3-yl)acetamide 
• 1227911-38-7 tert-butyl 3-[bis(tert-butoxycarbonyl)amino]-6-bromo-indazole-1-carboxylate 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol-1-yl)acetamide derivatives as potent VEGFR-2 inhibitors

Vascular endothelial growth factor-2 (VEGFR-2) plays a pivotal role in tumor angiogenesis. Herein, a library of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol -1-yl)acetamide derivatives were designed and synthesized as VEGFR-2 inhibitors based on scaffold hopping strategy. These compounds exhibited the excellent inhibitory in both VEGFR-2 and tumor cells proliferation. Especially, compound W13 possessed potent VEGFR-2 inhibition with IC50 = 1.6 nM and anti-proliferation against HGC-27 tumor cells with IC50 = 0.36 ± 0.11 μM, as well as less toxicity against normal GES-1 cells with IC50 = 187.46 ± 10.13 μM. Moreover, W13 obviously inhibited colony formation, migration and invasion of HGC-27 cells by adjusting the expression of MMP-9 and E-cadherin, and induced HGC-27 cells apoptosis by increasing ROS production and regulating the expression of apoptotic proteins. Furthermore, W13 blocked the PI3K-Akt-mTOR signaling pathway in HGC-27 cells. In addition, anti-angiogenesis of W13 was proved by inhibiting tube formation and the expression of p-VEGFR-2 in HUVEC cells. All the results demonstrated that W13 could be developing as a promising anticancer agent for gastric cancer therapy.

Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer

Fibroblast growth factor receptor 4 (FGFR4) is a member of the fibroblast growth factor receptor family, which is closely related to the occurrence and development of hepatocellular carcinoma (HCC). In this article, a series of indazole derivatives were designed and synthesized by using computer-aided drug design (CADD) and structure-based design strategies, and then they were evaluated for their inhibition of FGFR4 kinase and antitumor activity. F-30 was subtly selective for FGFR4 compared to FGFR1; it affected cell growth and migration by inhibiting FGFR4 pathways in HCC cell lines in a dose-dependent manner.

From Fragment to Lead: De Novo Design and Development toward a Selective FGFR2 Inhibitor

Fibroblast growth factor receptors (FGFRs) are implicated in a range of cancers with several pan-kinase and selective-FGFR inhibitors currently being evaluated in clinical trials. Pan-FGFR inhibitors often cause toxic side effects and few examples of subtype-selective inhibitors exist. Herein, we describe a structure-guided approach toward the development of a selective FGFR2 inhibitor. De novo design was carried out on an existing fragment series to yield compounds predicted to improve potency against the FGFRs. Subsequent iterative rounds of synthesis and biological evaluation led to an inhibitor with nanomolar potency that exhibited moderate selectivity for FGFR2 over FGFR1/3. Subtle changes to the lead inhibitor resulted in a complete loss of selectivity for FGFR2. X-ray crystallographic studies revealed inhibitor-specific morphological differences in the P-loop which were posited to be fundamental to the selectivity of these compounds. Additional docking studies have predicted an FGFR2-selective H-bond which could be utilized to design more selective FGFR2 inhibitors.

INHIBITORS OF ENL/AF9 YEATS

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.

Design, synthesis and biological evaluation of novel 1H-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.

Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety

As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-AblWT and Bcr-AblT315I in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-AblWT and Bcr-AblT315I kinases with IC50 of 0.043 μM and 0.17 μM, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 μM and 5.42 μM, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization.

Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold

Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9 μM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.

Lewis-acid Promoted Chemoselective Condensation of 2-Aminobenzimidazoles or 3-Aminoindazoles with 3-Ethoxycyclobutanones to Construct Fused Nitrogen heterocycles

A Lewis-acid promoted chemoselective condensation of 2-aminobenzimidazoles or 3-aminoindazoles with 3-ethoxycyclobutanones is presented. Diverse fused heterocycles benzo[4,5]-imidazo[1,2-a]pyrimidine and pyrimido[1,2-b]-indazole derivatives were obtained in moderate to high yields under mild conditions, the reaction mechanism of which was in sharp contrast to previous [3+3] annulation reaction of 3-ethoxycyclobutanones. (Figure presented.).

Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors

Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1?nM, FGFR2: 2.0?±?0.8?nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC50 values of 25.3?±?4.6?nM and 77.4?±?6.2?nM respectively.

Indazoles compound and its preparation and use (by machine translation)

This invention belongs to the field of medicine synthesis, relates to novel indazoles, preparation method and application thereof, and containing said compounds as pharmaceutical composition of the active ingredient, and for preparing same as a medicament for the treatment of diseases related to tyrosine kinase FGFR, in particular of the FGFR associated the use of the medicament of cancer. Indazoles of this invention shown in a chemical formula represented by the following formula I, wherein the substituents are as defined in the specification; the compound by biological experimental results show that, for the fibroblast growth factor receptor (FGFR) has good inhibitory activity, can be used as a preparation for prevention and treatment of diseases associated with FGFR pharmaceutical, in particular for preparing and treating of FGFR-related cancer. (by machine translation)