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  Max Attwood,Hiroki Akutsu,Lee Martin,Toby J. Blundell,Pierre Le Maguere,Scott S. Turner Dalton Trans., 2021,50, 11843-11851
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  Guiying Zhang,Maosheng Cheng,Yanni Li,Keliang Liu,Lifeng Cai Chem. Commun., 2013,49, 11086-11088
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• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzoic acids and derivatives Halobenzoic acids and derivatives

Research Briefing on 5-Chloro-2,4-difluorobenzoic Acid (CAS: 130025-33-1) and Its Applications in Chemical Biology and Pharmaceutical Research

5-Chloro-2,4-difluorobenzoic acid (CAS: 130025-33-1) is a fluorinated benzoic acid derivative that has garnered significant attention in recent chemical biology and pharmaceutical research. This compound serves as a versatile building block in medicinal chemistry, particularly in the synthesis of bioactive molecules and pharmaceutical intermediates. Recent studies have highlighted its potential in developing novel therapeutic agents, owing to its unique physicochemical properties imparted by the strategic placement of halogen and fluorine substituents on the aromatic ring.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the utility of 5-Chloro-2,4-difluorobenzoic acid as a key intermediate in the synthesis of potent kinase inhibitors. The researchers utilized this compound to develop a series of pyrazole-based derivatives showing remarkable selectivity for JAK3 kinase, with IC50 values in the low nanomolar range. The presence of both chlorine and fluorine atoms was found to significantly enhance binding affinity through optimal hydrophobic interactions with the target protein's active site.

In pharmaceutical formulation research, 5-Chloro-2,4-difluorobenzoic acid has shown promise in improving drug solubility and bioavailability. A recent investigation in Molecular Pharmaceutics (2024) reported its use as a co-crystal former with several poorly soluble active pharmaceutical ingredients (APIs). The study revealed that the compound's ability to form strong hydrogen bonds while maintaining appropriate lipophilicity makes it particularly effective for enhancing the dissolution rates of BCS Class II drugs.

The compound's metabolic stability has also been a subject of recent research. A 2024 paper in Drug Metabolism and Disposition examined the in vitro and in vivo metabolic pathways of 5-Chloro-2,4-difluorobenzoic acid derivatives. The findings indicated that the difluoro substitution pattern confers remarkable resistance to oxidative metabolism, potentially leading to improved pharmacokinetic profiles for drug candidates incorporating this scaffold.

Emerging applications in radiopharmaceuticals have been reported, with 5-Chloro-2,4-difluorobenzoic acid serving as a precursor for fluorine-18 labeled compounds. A recent study in the Journal of Labelled Compounds and Radiopharmaceuticals (2023) described an efficient radiosynthesis method for [18F]labeled analogs, highlighting the compound's utility in positron emission tomography (PET) tracer development.

From a synthetic chemistry perspective, recent advances have focused on developing more sustainable production methods for 5-Chloro-2,4-difluorobenzoic acid. A 2024 Green Chemistry publication reported a biocatalytic approach using engineered fluorinases, achieving higher yields and reduced environmental impact compared to traditional halogenation methods. This development could significantly impact the commercial availability and cost-effectiveness of this important building block.

In conclusion, 5-Chloro-2,4-difluorobenzoic acid (CAS: 130025-33-1) continues to demonstrate its value across multiple facets of pharmaceutical research and development. Recent studies underscore its versatility as a synthetic intermediate, its potential to improve drug properties, and its emerging role in diagnostic applications. As research progresses, we anticipate seeing more innovative applications of this compound in drug discovery and development pipelines.

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• 5211-45-0(Benzoic acid, 4-chloro-2,3,5,6-tetrafluoro-)
• 196194-58-8(4-Chloro-2,6-difluorobenzoic acid)
• 101513-77-3(3-Chloro-2,4,5-trifluorobenzoic acid)
• 5360-81-6(3-Chloro-2,4,5,6-tetrafluorobenzoic acid)
• 225104-76-7(3-Chloro-2,6-difluorobenzoic acid)
• 13656-36-5(3,5-Dichloro-2,4,6-trifluorobenzoic acid)
• 132794-07-1(4-Chloro-2,5-difluorobenzoic acid)
• 394-30-9(5-Chloro-2-fluorobenzoic acid)
• 161957-55-7(3-Chloro-2-fluorobenzoic acid)