2-Bromopyridine-4-carboxylic Acid CAS 66572-56-3

The most fundamental and widely used biological application is as a biochemical reagent. In life science research, it can serve as a biomaterial or organic compound, serving various experimental scenarios such as drug screening, target validation, and signal pathway research. This compound belongs to the category of biochemical reagents, and its molecular structure carries two highly reactive functional groups, bromine atom and carboxyl group, which makes it highly flexible in subsequent derivatization reactions.

Researchers can use bromine atoms for Suzuki coupling, Buchwald coupling, nucleophilic substitution, and other carbon carbon carbon or carbon heteroatom bond construction reactions. They can also convert carboxyl groups into derivatives such as esters, amides, and hydrazide, thereby rapidly constructing structurally diverse compound libraries. It is precisely this "bifunctional" chemical property that makes it a widely used universal block in chemical biology laboratories.

In specific target screening experiments, it has been directly applied to the screening of RMI-FANCM protein interaction inhibitors.

The experiment aims to search for small molecule compounds that can interfere with the interaction between RMI protein and FANCM protein, and their derivatives are among the candidate molecules in this screening system. The RMI-FANCM interaction plays a critical role in the DNA damage repair pathway, and inhibiting it may provide a new entry point for anti-tumor strategies. This application fully demonstrates that it is not only a synthetic raw material, but also can directly participate in biological activity evaluation in the form of the parent material.

The application of acid in anti-tumor biology research is particularly prominent. The National Cancer Institute (NCI) in the United States has included it in the human tumor cell line growth inhibition experimental system and conducted systematic activity testing on multiple cancer cell lines. Specifically, in NCI human tumor cell line growth inhibition experiment, 2-bromine - was used for single dose screening of MCF7 breast cancer cell line and IGROV1 ovarian cancer cell line.

MCF7 is an estrogen receptor positive human breast cancer cell line, which is a classic model to study the drug sensitivity of hormone dependent breast cancer; IGROV1 is a cell line derived from ovarian cancer patients and has varying degrees of sensitivity to various chemotherapy drugs. The experimental results showed that its derivatives exhibited certain growth inhibitory activity in these cell lines, providing important lead compound clues for the subsequent development of anti-tumor drugs based on pyridine carboxylic acid skeleton.

It is worth noting that the anti-tumor potential of 2-bromo-4-pyridinecarboxylic acid compound is not limited to the cellular level. In further pharmaceutical chemistry research, it has been confirmed as a key synthetic material for fluorinated and nitrogen-containing heterocyclic drugs, including the synthesis of JAK inhibitors. JAK (Janus kinase) is a core kinase in the cytokine signaling pathway, and JAK inhibitors are an important class of drugs for treating autoimmune diseases such as bone marrow fibrosis, rheumatoid arthritis, atopic dermatitis, and hematological tumors. Through the cross coupling reaction involving its bromine atom, efficient construction of JAK inhibitor frameworks containing pyridine rings can be achieved, making it an indispensable component in this high-value pharmaceutical field.

In addition, it has also played an important role in the discovery and research of VEGFR-2 inhibitors. VEGFR-2 (vascular endothelial growth factor receptor 2) is a key regulatory factor in tumor angiogenesis, and inhibiting VEGFR-2 can effectively block the blood supply to tumors, thereby inhibiting tumor growth. In related studies, a series of bis (arylurea) VEGFR-2 inhibitors were successfully synthesized using it as the starting material through Suzuki coupling reaction with arylboronic acid. These compounds demonstrated excellent activity in the exploration of hinge region binding fragments, demonstrating their powerful ability as drug molecular skeleton building units.

In addition to the field of anti-tumor, the development of metabolic enzyme inhibitors also has important value. A typical case is its application in the development of mouse triglyceride lipase (ATGL) inhibitors. ATGL is a rate limiting enzyme in lipid metabolism, catalyzing the first step reaction of triglyceride hydrolysis, and has a critical impact on the occurrence and development of metabolic diseases such as obesity, insulin resistance, and non-alcoholic fatty liver disease. Researchers synthesized a series of derivatives using it as the parent nucleus and evaluated its ATGL inhibitory activity through systematic structure-activity relationship studies.

The results indicate that compounds based on this skeleton have moderate to good inhibitory activity against ATGL, providing valuable lead structures for the development of novel anti obesity and anti metabolic syndrome drugs. This application fully demonstrates its unique advantages in chemical biology: the nitrogen atom on its pyridine ring can form hydrogen bonds or coordinate with amino acid residues in the enzyme active site, while bromine atoms and carboxyl groups provide abundant derivatization sites, allowing researchers to finely regulate the physicochemical properties and selectivity of the molecule while maintaining the core pharmacophore.

In the broader field of medicinal chemistry, 2-Bromopyridine-4-carboxylic acid is used as a universal intermediate for the modification and synthesis of drug molecular structures. The pyridine ring is one of the most common heterocycles in drug molecules. According to statistics, over 20% of marketed small molecule drugs contain pyridine or its reduced product, the pyridine ring.

Provided a pyridine platform with pre-set bromine and carboxyl atoms, enabling medicinal chemists to efficiently carry out structural modifications in two directions: one is to use bromine atoms for various palladium catalyzed cross coupling reactions, introducing aromatic, vinyl, alkyl and other functional groups to rapidly expand the structural diversity of molecules; The second is to use carboxyl groups for amidation, esterification, reduction and other reactions to regulate the polarity, solubility and pharmacokinetic properties of molecules.

In the synthesis of protein receptor antagonists, it is also an important starting material. For example, in the study of synthesizing a class of 2-aryl-4- (1H-pyrazol-3-yl) pyridine LSD1/HDAC dual target inhibitors, 2-bromo-4-iodopyridine (highly correlated with the structure of 2-bromo-4-pyridinecarboxylic acid) was used as a key intermediate, and a compound with dual epigenetic regulatory activity was constructed by Suzuki coupling and pyrazole boronic acid reaction. These dual target inhibitors have demonstrated unique advantages in the treatment of hematological and solid tumors, and the starting point of their synthetic route is the bromopyridine block represented by bromopyridine carboxylic acid.