1000342-11-9

Usage

Uses

Used in Pharmaceutical Research:
Methyl 3-amino-5-bromo-2-methylbenzoate is utilized as a key intermediate in the development of new drugs and active pharmaceutical ingredients. Its unique chemical structure allows for the creation of various drug candidates with potential therapeutic applications.
Used in Organic Synthesis:
In the field of organic synthesis, Methyl 3-amino-5-bromo-2-methylbenzoate serves as a versatile building block for the synthesis of other organic compounds and materials. Its presence of functional groups, such as the bromine atom and amino group, enables further chemical reactions and modifications, leading to the formation of a wide range of organic products.
Used in Production of Other Organic Compounds and Materials:
Methyl 3-amino-5-bromo-2-methylbenzoate may also be employed as an intermediate in the production of other organic compounds and materials. Its unique structure and properties make it a valuable component in the synthesis of various chemical products, contributing to the advancement of the chemical industry.

InChI:InChI=1S/C9H10BrNO2/c1-5-7(9(12)13-2)3-6(10)4-8(5)11/h3-4H,11H2,1-2H3

Upstream product

• 59382-59-1 2-methyl-3-nitro-benzoic acid methyl ester 
• 79669-49-1 5-bromo-2-methylbenzoic acid 
• 1975-50-4 2-methyl-3-nitrobenzic acid 
• 220514-28-3 5-bromo-2-methyl-3-nitrobenzoic acid methyl ester 
• 107650-20-4 5-bromo-2-methyl-3-nitro-benzoic acid 

Downstream Products

• 1403257-14-6 methyl 5-bromo-3-(cyclopentyl(methyl)amino)-2-methylbenzoate 
• 1403257-15-7 5-bromo-3-(cyclopentyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide 
• 1403257-17-9 5-(cyclopentyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4'-formyl-4-methyl-[1,1'-biphenyl]-3-carboxamide 
• 1403254-55-6 EPZ₀₀₆₀₈₈ 
• 1403254-56-7 5-(cyclopentylamino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4'-((dimethylamino)methyl)-4-methyl-[1,1'-biphenyl]-3-carboxamide 
• 1403257-18-0 5-bromo-3-(cyclopentylamino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide 
• 1403258-26-3 methyl 5-bromo-3-(((trans)-4-((tert-butoxycarbonyl)amino)cyclohexyl)-amino)-2-methylbenzoate 
• 1403259-16-4 methyl 5-bromo-3-((4-(cis)-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-2-methylbenzoate 
• 1403258-65-0 5-bromo-3-[(2,2-difluoroethyl)(oxan-4-yl)amino]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-methylbenzamide 
• 1403258-64-9 5-bromo-3-[(2,2-difluoroethyl)(oxan-4-yl)amino]-2-methylbenzoic acid 
• 1403258-63-8 methyl 5-bromo-3-[(2,2-difluoroethyl)(oxan-4-yl)amino]-2-methylbenzoate 
• 1403256-16-5 5-((2,2-difluoroethyl)(tetrahydro-2H-pyran-4-yl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide 
• 1403258-58-1 5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-((2-methoxyethyl)(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide 
• 1403258-57-0 methyl 5-bromo-3-((2-methoxyethyl)(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate 

Relevant academic research and scientific papers

The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor

By targeting the unique Cys663 of EZH2, SKLB-0335 displays high paralog-selectivity on EZH2. Biochemical studies show that SKLB-0335 can covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibit H3K27Me3. SKLB-0335 could be an effective chemical probe with which to further investigate the specific biological functions of EZH2.

Synthesis and evaluation of a novel series of 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid-substituted amide derivatives as anticancer, antiangiogenic, and antioxidant agents

A series of novel indazole derivatives has been synthesized and evaluated for anticancer, antiangiogenic, and antioxidant activities. The capability of the synthesized compounds 11a–x to hinder the viability of three human cancer cells lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60 (leukemia), were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 11a–x screened, 11c and 11d showed the higher inhibitory activity on the viability of HEP3BPN 11 (liver), when compared with the standard methotrexate. These compounds were further tested to evaluate their potential to inhibit the proangiogenic cytokines associated with tumor development. Compound 11c was found to be a potent antiangiogenic agent against TNFα, VEGF, and EGF, whereas 11d showed potent antiangiogenic activity against TNFα, VEGF, IGF1, TGFb, and leptin inhibition. All the compounds 11a–x were screened for their antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging activity. Compounds 11n, 11p, 11q, and 11v have shown significant OH radical scavenging activities, also compounds 11c, 11h, and 11k were found to have a DPPH radical scavenging activity and compounds 11a and 11m exhibited better SOR scavenging activity when compared with the reference compound ascorbic acid. In silico molecular docking analysis revealed important structural insights behind observed anti TNFα effect by present indazole compounds.

X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson’s Disease

Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson’s disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1H-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to23, which manifested IC50values of 0.64 and 0.04 μM to hIDO1 and hTDO, respectively, and had good pharmacokinetic properties and brain penetration in mice.23showed efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-PD medicine. Further studies revealed that different from Madopar,23likely has specific anti-PD mechanisms involving lowering IDO1 expression, alleviating dopaminergic neurodegeneration, reducing inflammatory cytokines and quinolinic acid in mouse brain, and increasing kynurenic acid in mouse blood.

SKLB1039 Compound as well as preparation method and application thereof

The invention belongs to the technical field of preparation of new compounds, and particularly relates SKLB1039 compound as well as a preparation method and application thereof. The 2 -methyl -3 -nitrobenzoic acid is taken as an initial raw material and is brominated. Esterification, reduction, reductive amination and hydrolysis synthesis 5 - bromo -2 - methyl -3 - (N - ethyl, N - (tetrahydropyran -4 - yl)) aminobenzoic acid. The cyclohexanone serving as a raw material is subjected to catalytic hydrogenation reduction of carbonyl α, acetyl cyclohexanone and cyanopyridone to synthesize 4 - aminomethyl -1 - methyl -5, 6, 7, 8 - tetrahydroisoquinoline -3 (2H) - ketone. Coupling the two to an amide is followed by catalytic coupling with an aryl sheet to give SKLB1039 a compound. SKLB1039 Large-scale preparation technology is provided, operation is easy, the post-treatment purification process is simple, the total route yield is improved, raw materials are easy to purchase, the price is low, and the production cost is greatly reduced.

Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2

EZH2 mediates both PRC2-dependent gene silencing via catalyzing H3K27me3 and PRC2-independent transcriptional activation in various cancers. Given its oncogenic role in cancers, EZH2 has constituted a compelling target for anticancer therapy. However, current EZH2 inhibitors only target its methyltransferase activity to downregulate H3K27me3 levels and show limited efficacy because of inadequate suppression of the EZH2 oncogenic activity. Therefore, therapeutic strategies to completely block the oncogenic activity of EZH2 are urgently needed. Herein, we report a series of EZH2-targeted proteolysis targeting chimeras (PROTACs) that induce proteasomal degradation of PRC2 components, including EZH2, EED, SUZ12, and RbAp48. Preliminary assessment identified E7 as the most active PROTAC molecule, which decreased PRC2 subunits and H3K27me2/3 levels in various cancer cells. Furthermore, E7 strongly inhibited transcriptional silencing mediated by EZH2 dependent on PRC2 and transcriptional activation mediated by EZH2 independent of PRC2, showing significant antiproliferative activities against cancer cell lines dependent on the enzymatic and nonenzymatic activities of EZH2.

Bifunctional compound capable of inducing PRC2 protein complex core subunit degradation, pharmaceutical composition and application

The invention discloses a bifunctional compound capable of inducing PRC2 protein complex core subunit degradation, a pharmaceutical composition and application. The bifunctional compound comprises a compound as shown in any one of formulas I-III, a pharmaceutically acceptable salt or prodrug thereof, a solvate thereof, a hydrate thereof, a polymorphic substance thereof, a tautomer thereof, a stereoisomer thereof or an isotope substituted compound thereof, wherein n in the formulas I-III is an integer from 1 to 10, X is O, N or S, and Y is O, H2 or S. The bifunctional compound can effectively induce degradation of a core subunit of a PRC2 protein complex, so that cancers mediated by the PRC2 complex and subunits thereof including EZH2, EED, SUZ12, RbAp46 and RbAp48 are treated, and the carcinogenic activity of the subunits of the PRC2 complex is completely blocked.

Small molecule compound based on EZH2 protein degradation, and application thereof

The invention discloses a series of small molecule compounds capable of selectively degrading EZH2 protein, and application thereof. The compounds can be prepared into proper pharmaceutical dosage forms for EZH2-mediated related tumor treatment.

POLYSUBSTITUTED BENZENE COMPOUND AND PREPARATION METHOD AND USE THEREOF

The present invention provides a novel EZH2 inhibitor compound represented by formula (I) and a use of the inhibitor compound in preventing or treating a disease mediated by EZH2.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

Design and synthesis of (E)-1,2-diphenylethene-based EZH2 inhibitors

Enhancer of zeste homolog 2 (EZH2) serves as the catalytic subunit of the polycomb repression complex 2 (PRC2), which is implicated in cancer progression metastasis and poor prognosis. Based on our EZH2 inhibitor SKLB1049 with low nanomolar activity, we e