20731-48-0

Usage

Uses

Used in Pharmaceutical Industry:
3-Bromo-4,5-dimethoxybenzoic acid is used as a key intermediate in the synthesis of various pharmaceuticals for its potential biological activities, such as antimalarial and anticancer properties. Its unique structure allows for the development of new drugs with improved efficacy and reduced side effects.
Used in Agrochemical Industry:
In the agrochemical industry, 3-Bromo-4,5-dimethoxybenzoic acid serves as an intermediate in the production of agrochemicals, contributing to the development of effective pesticides and other agricultural chemicals that protect crops and enhance agricultural productivity.
Used in Organic Synthesis:
3-Bromo-4,5-dimethoxybenzoic acid is utilized as a building block in organic synthesis for creating more complex molecules. Its versatile structure allows chemists to modify and functionalize it to synthesize a wide range of organic compounds with diverse applications.
It is crucial to handle and use 3-Bromo-4,5-dimethoxybenzoic acid with caution due to its potential hazards and toxicity. Proper safety measures and guidelines should be followed to minimize risks associated with its use.

InChI:InChI=1/C9H9BrO4/c1-13-7-4-5(9(11)12)3-6(10)8(7)14-2/h3-4H,1-2H3,(H,11,12)

Upstream product

• 6948-30-7 5-bromoveratralaldehyde 
• 50772-79-7 methyl 5-bromo-3,4-dimethoxybenzoate 
• 781654-31-7 3-bromo-4,5-dimethoxybenzonitrile 
• 91004-48-7 4,5-Dimethoxy-3-nitrobenzoic acid 
• 6324-52-3 3-bromo-4-hydroxy-5-methoxybenzoic acid 
• 77-78-1 dimethyl sulfate 
• 64-19-7 acetic acid 
• 2973-76-4 5-bromo-4-hydroxy-3-methoxybenzaldehyde 
• 121-33-5 vanillin 
• 861522-34-1 2-acetylamino-3,4-dimethoxy-benzoic acid 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 93-07-2 Veratric acid 
• 121-34-6 3-methoxy-4-hydroxybenzoic acid 
• 861522-33-0 2-acetylamino-5-bromo-3,4-dimethoxy-benzoic acid 

Downstream Products

• 92698-07-2 3-bromo-4,5-dimethoxy-benzoic acid-(2-diethylamino-ethyl ester); hydrochloride 
• 1916-08-1 3-hydroxy-4,5-dimethoxybenzoic acid 
• 70574-46-8 3-bromo-4,5-dimethoxybenzoyl chloride 
• 712294-58-1 3-bromo-4,5-dimethoxybenzamide 
• 93-07-2 Veratric acid 

Relevant academic research and scientific papers

Structure-Activity Relationship of Phenylpyrazolones against Trypanosoma cruzi

Chagas disease is a neglected parasitic disease caused by the parasitic protozoan Trypanosoma cruzi and currently affects around 8 million people. Previously, 2-isopropyl-5-(4-methoxy-3-(pyridin-3-yl)phenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0227) was discovered to be a sub-micromolar inhibitor (pIC50=6.4) of T. cruzi. So far, SAR investigations of this scaffold have focused on the alkoxy substituent, the pyrazolone nitrogen substituent and the aromatic substituent of the core phenylpyrazolone. In this study, modifications of the phenyldihydropyrazolone scaffold are described. Variations were introduced by installing different substituents on the phenyl core, modifying the geminal dimethyl and installing various bio-isosteres of the dihydropyrazolone group. The anti T. cruzi activity of NPD-0227 could not be surpassed as the most potent compounds show pIC50 values of around 6.3. However, valuable additional SAR data for this interesting scaffold was obtained, and the data suggest that a scaffold hop is feasible as the pyrazolone moiety can be replaced by a oxazole or oxadiazole with minimal loss of activity.

Glutathione conjugation and protein adduction derived from oxidative debromination of benzbromarone in mice

Benzbromarone (BBR), a uricosuric agent, has been known to induce hepatotoxicity, and its toxicity has a close relation to cytochrome P450-mediated metabolic activation. An oxidative debromination metabolite of BBR has been reported in microsomal incubations. The present study attempted to define the oxidative debromination pathway of BBR in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolitewere detected in BBR-treated mice after solid phase extraction.M1 andM2 shared the same chromatographic behavior and mass spectral identities as those detected in N-acetylcysteine/GSHand BBR-fortified microsomal incubations. The structure of M1 was characterized by chemical synthesis, along with mass spectrometry analysis. In addition, hepatic protein modification that occurs at cysteine residues (M93) was observed in mice given BBR. The observed protein adduction reached its peak 4 hours after administration and occurred in a dose-dependent manner. A GSH conjugate derived from oxidative debromination of BBR was detected in livers of mice treated with BBR, and the formation of the GSH conjugate apparently took place earlier than the protein adduction. In summary, our in vivo work provided strong evidence for the proposed oxidative debromination pathway of BBR, which facilitates the understanding of the mechanismsof BBR-induced hepatotoxicity. SIGNIFICANCE STATEMENT This study investigated the oxidative debromination pathway of benzbromarone (BBR) in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolite were detected in BBR-treated mice. M1 and M2 were also observed in microsomal incubations. The structure of M1 was characterized by chemical synthesis followed by mass spectrometry analyses. More importantly, protein adduction derived fromoxidative debromination ofBBR(M93) was observed in mice given BBR, and occurred in dose- and time-dependent manners. The success in detection of GSH conjugate, urinary N-acetylcysteine conjugate, and hepatic protein adduction in mice given BBR provided solid evidence for in vivo oxidative debromination of BBR. The studies allowed a better understanding of the metabolic activation of BBR.

Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents

A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure-activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diarylpyrazoles. Isoxazoles 3 with 3,4,5-trimethoxy-substituted ring A and 3-hydroxy-4-methoxy-substituted ring B were more active than the respective pyrazoles 1. Of the azoles substituted with the same set of other aryl pharmacophores, diarylpyrazoles 1, 4,5-diarylisoxazoles 3, and 4,5-diaryl-1,2,3-triazoles 7 displayed similar strongest antimitotic antitubulin effect followed by 3,4-diarylisoxazoles 5, 1,5-diaryl-1,2,3-triazoles 8, and pyrroles 10 that showed the lowest activity. Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazoles, whereas potency of the respective 3,4-diarylisoxazoles was increased.

Discovery and evaluation of the hybrid of bromophenol and saccharide as potent and selective protein tyrosine phosphatase 1B inhibitors

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway. Inhibition of PTP1B is expected to improve insulin action. Appropriate selectivity and permeability are the gold standard for excellent PTP1B inhibitors. In this work, molecular hybridization-based screening identified a selective competitive PTP1B inhibitor. Compound 10a has IC50 values of 199?nM against PTP1B, and shows 32-fold selectivity for PTP1B over the closely related phosphatase TCPTP. Molecule docking and molecular dynamics studies reveal the reason of selectivity for PTP1B over TCPTP. Moreover, the cell permeability and cellular activity of compound 10a are demonstrated respectively.

Novel bioactivation pathway of benzbromarone mediated by cytochrome P450

Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl) benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity.

Synthesis and biological activities of new halophenols

A series of new halophenols were synthesized, and their structures were established on the basis of 1H, 13C NMR and mass spectral data. All of the prepared compounds were screened for their in vitro protein tyrosine kinase (PTK) and vascular smooth muscle cell (VSMC) proliferation inhibitory activity. Twelve halophenols showed significant PTK inhibitory activity, most of them exhibited stronger activities than that of genistein, a positive reference compound. Several halophenols also displayed moderate VSMC proliferation inhibitory activity, compound 8c showed higher activity than that of tetrandrine, a positive reference compound. The preliminary structure-activity relationships of these compounds were investigated and discussed. The results provided a foundation for the action mechanism study and further structure optimization of the halophenols.

Design, synthesis, and biological evaluation of bromophenol derivatives as protein tyrosine phosphatase 1B inhibitors

3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC 50 = 1.7 μmol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure-activity relationship indicated that the tricyclic scaffold and multi-bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC50 of 0.89 μmol/L, which was approximately two-fold more potent than the initial lead compound BDB.

N-HYDROXYAMIDE DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY

Novel N-hydroxyamide derivatives are disclosed. These N-hydroxyamide derivatives inhibit UPD-3O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase, an enzyme present in gram negative bacteria and are therefore useful as antimicrobials and antibiotics. Methods of synthesis and of use of the compounds are also disclosed.