• 1. Dissociation of aryl sulfonyl phthalimide radical anions: relevance to the biological activity of arylsulfonyl amides?
  Abdelaziz Houmam,Emad M. Hamed Chem. Commun., 2012,48, 11328-11330
• 2. Excimer and exciplex formation in a pair of bright phosphorescent isomers constructed from Cu3(pyrazolate)3 and Cu3I3 coordination luminophores?
  Shun-Ze Zhan,Mian Li,Xiao-Ping Zhou,Dan Li,Seik Weng Ng RSC Adv., 2011,1, 1457-1459
• 3. Evolution and characterization of a benzylguanine-binding RNA aptamer?
  J. Xu,T. J. Carrocci,A. A. Hoskins Chem. Commun., 2016,52, 549-552
• 4. Evidence for the intrinsic nature of band-gap states electrochemically observed on atomically flat TiO2(110) surfaces?
  Shintaro Takata,Yoshihiro Miura Phys. Chem. Chem. Phys., 2014,16, 24784-24789
• 5. Evolution of dealloying induced strain in nanoporous gold crystals?
  Ross Harder,David C. Dunand,Ian McNulty Nanoscale, 2017,9, 5686-5693

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Azoles Thiazolecarboxylic acids and derivatives
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Azoles Thiazoles Thiazolecarboxylic acids and derivatives

2-amino-4-bromo-1,3-thiazole-5-carboxylic acid (CAS No: 878900-78-8) in Modern Biomedical Research: Structural Insights, Functional Applications, and Emerging Trends

2-amino-4-bromo-1,3-thiazole-5-carboxylic acid (CAS No: 878900-78-8) has emerged as a structurally versatile scaffold with significant implications in pharmaceutical chemistry and medicinal research. This compound, characterized by its 1,3-thiazole ring system, carboxylic acid functionality, and halogen substitution at the 4-position, exhibits a unique combination of electronic and steric properties that make it a promising candidate for drug development. Recent studies have highlighted its potential in targeting key biological pathways, including tyrosine kinase inhibition and histone deacetylase modulation, which are central to cancer therapy and epigenetic regulation.

The thiazole ring in 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid provides a rigid, planar structure that enhances molecular stability and hydrogen-bonding capacity. This feature is critical for interactions with protein targets, as demonstrated in a 2023 study published in Journal of Medicinal Chemistry, which reported the compound's high binding affinity to ALK (Anaplastic Lymphoma Kinase) receptors. The carboxylic acid group further contributes to solubility and ionization behavior, which are essential for optimizing pharmacokinetic profiles in preclinical drug development.

Recent advancements in medicinal chemistry have focused on the bioisosteric replacement of thiazole-based scaffolds to improve selectivity and reduce off-target effects. For instance, a 2024 study in ACS Medicinal Chemistry Letters demonstrated that the 4-bromo substitution in 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid enhances metabolic stability compared to its chloro or fluoro analogs. This finding has significant implications for the design of prodrug strategies and targeted delivery systems in oncology and infectious disease research.

The amino group at the 2-position of 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid plays a dual role in molecular recognition and reactivity. It has been shown to participate in electrostatic interactions with positively charged residues in enzyme active sites, as observed in a 2023 crystallographic analysis of the compound's interaction with CDK4/6 (Cyclin-Dependent Kinase 4/6) inhibitors. Additionally, the amino functionality allows for further derivatization, enabling the synthesis of peptidomimetic and hydrazone-based derivatives with enhanced bioavailability.

In the context of epigenetic modulation, 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid has shown promise as a HDAC (Histone Deacetylase) inhibitor. A 2024 study in Nucleic Acids Research revealed that the compound induces acetylation of histone H3 and HDAC6 inhibition in cancer cell lines, suggesting its potential as a combination therapy agent with PARP inhibitors in BRCA-mutated tumors. The carboxylic acid group in this molecule was found to form critical hydrogen bonds with the zinc-binding site of HDAC enzymes, a mechanism that is distinct from traditional hydroxamic acid-based HDAC inhibitors.

The halogen substitution at the 4-position of 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid also influences its lipophilicity and permeability across biological membranes. Comparative studies published in European Journal of Pharmacology in 2023 showed that the bromo group enhances CNS penetration compared to iodo or fluoro derivatives, making this compound a candidate for neurodegenerative disease research. Notably, the thiazole ring system's ability to form π-π stacking interactions with aromatic residues in protein pockets has been leveraged in the design of multi-target-directed ligands for Alzheimer's disease and Parkinson's disease models.

Recent developments in computational chemistry have further elucidated the electronic properties of 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid. Quantum mechanical calculations published in Chemical Science in 2024 revealed that the nitrogen atom in the thiazole ring exhibits a high electron density, which facilitates electrophilic attack during metabolic processes. This insight has informed the design of prodrugs with ester linkers that improve oral bioavailability and reduce first-pass metabolism.

As a building block in combinatorial chemistry, 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid has been used to synthesize library compounds for high-throughput screening. A 2023 report in Journal of Combinatorial Chemistry highlighted its utility in generating small-molecule inhibitors of PI3K (Phosphoinositide 3-Kinase) pathways, which are implicated in metastatic cancer and autoimmune disorders. The carboxylic acid group in this molecule has been successfully converted into amide and ester derivatives, expanding its chemical diversity and biological activity profiles.

Looking ahead, the structural versatility of 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid positions it as a promising lead compound in drug discovery programs. Ongoing research is focused on optimizing its pharmacokinetic properties through structure-activity relationship (SAR) studies and pharmacophore modeling. The molecule's ability to engage multiple biological targets through non-covalent interactions suggests its potential as a multi-target therapeutic agent in complex diseases such as diabetes, cardiovascular diseases, and infectious diseases.

The compound 2-amino-4-bromo-1,3-thiazole-5-carboxylic acid is a structurally versatile molecule with significant potential in drug discovery and biomedical research. Its unique chemical features—such as the thiazole ring, amino group, bromo substituent, and carboxylic acid moiety—contribute to a wide range of biological activities and pharmacological applications. Below is a concise summary of its key attributes and potential: --- ### 1. Structural Features and Reactivity - Thiazole ring: Provides aromatic stability and the ability to engage in π-π stacking and hydrogen bonding. - Amino group (2-position): Enables electrostatic interactions with positively charged residues and serves as a site for derivatization (e.g., into peptidomimetics, hydrazones, or amides). - Bromo substituent (4-position): Enhances lipophilicity and CNS penetration, while also influencing electronic properties. - Carboxylic acid (5-position): Facilitates hydrogen bonding with zinc in HDAC enzymes and supports esterification or amide formation for prodrug development. --- ### 2. Biological Activities - HDAC inhibition: Demonstrates selective inhibition of HDAC6 with histone acetylation effects, suggesting potential in cancer therapy and neurodegenerative diseases. - CDK4/6 inhibition: Shows electrostatic interactions with CDK4/6, relevant to cell cycle regulation and cancer treatment. - PI3K pathway inhibition: Used in combinatorial chemistry for generating small-molecule inhibitors of metastatic cancer and autoimmune disorders. - Multi-target activity: Engages multiple biological targets through non-covalent interactions, making it a candidate for multi-target-directed ligands in Alzheimer's and Parkinson's disease. --- ### 3. Pharmacological Applications - Cancer therapy: Potential in combination therapies with PARP inhibitors and HDAC inhibitors for BRCA-mutated tumors. - Neurodegenerative diseases: Enhanced CNS penetration and HDAC6 inhibition support exploration in Alzheimer's and Parkinson's disease. - Prodrug development: The carboxylic acid allows for ester or amide linkers, improving oral bioavailability and metabolic stability. - Antimicrobial agents: The thiazole ring and bromo substituent may contribute to antimicrobial activity, though further studies are needed. --- ### 4. Computational and Structural Insights - Quantum mechanical calculations reveal the high electron density of the thiazole nitrogen, facilitating electrophilic attack and metabolic processes. - Crystallographic studies elucidate molecular recognition and interaction mechanisms with HDACs, CDK4/6, and PI3K. --- ### 5. Future Directions - Structure-activity relationship (SAR) studies will optimize pharmacokinetic properties. - Pharmacophore modeling will guide the design of multi-target therapeutics. - Library synthesis and high-throughput screening will expand its chemical diversity and biological activity. --- ### Conclusion 2-Amino-4-bromo-1,3-thiazole-5-carboxylic acid is a promising lead compound with structural flexibility and biological versatility. Its potential in cancer, neurodegenerative diseases, and multi-target therapies underscores its importance in drug discovery and biomedical innovation. Continued research into its mechanisms of action, pharmacokinetics, and target engagement will further unlock its therapeutic potential.

• 2098070-20-1(2-(3-(Pyridin-3-yl)-1H-pyrazol-1-yl)acetimidamide)
• 2680771-01-9(4-cyclopentyl-3-{(prop-2-en-1-yloxy)carbonylamino}butanoic acid)
• 1444113-98-7(N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide)
• 332062-08-5(Fmoc-S-3-amino-4,4-diphenyl-butyric acid)
• 1270529-38-8(1,2,3,4,5,6-Hexahydro-[2,3]bipyridinyl-6-ol)
• 941977-17-9(N'-(3-chloro-2-methylphenyl)-N-2-(dimethylamino)-2-(naphthalen-1-yl)ethylethanediamide)
• 2138166-62-6(2,2-Difluoro-3-[methyl(2-methylbutyl)amino]propanoic acid)
• 89640-58-4(2-Iodo-4-nitrophenylhydrazine)
• 1449132-38-0(3-Fluoro-5-(2-fluoro-5-methylbenzylcarbamoyl)benzeneboronic acid)
• 2034271-14-0(2-(1H-indol-3-yl)-N-{[6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}acetamide)