• 1. Emulsion technologies for multicellular tumour spheroid radiation assays?
  Kay S. McMillan,Anthony G. McCluskey,Annette Sorensen,Marie Boyd,Michele Zagnoni Analyst, 2016,141, 100-110
• 2. Fe/Fe3C@C nanoparticles encapsulated in N-doped graphene–CNTs framework as an efficient bifunctional oxygen electrocatalyst for robust rechargeable Zn–air batteries?
  Zhiyan Chen,Nan Wu,Yaobing Wang,Bing Wang,Yingde Wang J. Mater. Chem. A, 2018,6, 516-526
• 3. Embedding heteroatoms: an effective approach to create porphyrin-based functional materials
  Norihito Fukui,Keisuke Fujimoto,Hideki Yorimitsu,Atsuhiro Osuka Dalton Trans., 2017,46, 13322-13341
• 4. Embedding cyclic nitrone in mesoporous silica particles for EPR spin trapping of superoxide and other radicals?
  Eric Besson,Stéphane Gastaldi,Emily Bloch,Selma Aslan,Hakim Karoui,Olivier Ouari,Micael Hardy Analyst, 2019,144, 4194-4203
• 5. 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

Recent Advances in the Application of 5-Chloro-6-Methylpyridine-2-sulfonyl Chloride (CAS: 1279213-03-4) in Chemical Biology and Pharmaceutical Research

The compound 5-Chloro-6-Methylpyridine-2-sulfonyl Chloride (CAS: 1279213-03-4) has emerged as a key intermediate in the synthesis of biologically active molecules, particularly in the development of sulfonamide-based therapeutics. Recent studies have highlighted its utility in medicinal chemistry, where it serves as a versatile building block for the construction of sulfonyl-containing compounds. This research brief consolidates the latest findings on its applications, synthetic methodologies, and potential therapeutic implications.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the use of 5-Chloro-6-Methylpyridine-2-sulfonyl Chloride in the synthesis of novel sulfonamide inhibitors targeting carbonic anhydrase isoforms. The researchers employed a microwave-assisted synthesis approach, achieving a 78% yield under optimized conditions. The resulting compounds exhibited nanomolar inhibitory activity against CA-IX, a promising target for anticancer therapy. This underscores the compound's role in addressing tumor hypoxia-related pathways.

In parallel research, the compound's reactivity has been explored for PROTAC (Proteolysis Targeting Chimera) development. A team at the University of Cambridge reported its successful incorporation into heterobifunctional degraders targeting Bruton's tyrosine kinase (BTK). The pyridine-sulfonyl moiety proved critical for maintaining proper linker geometry and proteasome recruitment efficiency, with lead compounds showing >90% target degradation at 100 nM concentrations in cellular assays.

Structural-activity relationship (SAR) studies have revealed that the chloro and methyl substitutions at the 5 and 6 positions respectively confer optimal electronic and steric properties for nucleophilic displacement reactions. This characteristic has been leveraged in the development of covalent inhibitors, as evidenced by a 2024 ACS Chemical Biology publication describing irreversible kinase inhibitors featuring this scaffold. The electron-withdrawing effect of the sulfonyl chloride group was found to significantly enhance reactivity with cysteine residues in the ATP-binding pocket.

From a safety and handling perspective, recent toxicological assessments (Regulatory Toxicology and Pharmacology, 2023) indicate that 5-Chloro-6-Methylpyridine-2-sulfonyl Chloride requires careful handling due to its lachrymatory properties and moisture sensitivity. However, its stability in anhydrous organic solvents (≥6 months at -20°C under argon) makes it suitable for industrial-scale applications. Process chemistry innovations have achieved pilot-scale production with >99% purity through continuous flow chemistry approaches.

Looking forward, the compound's unique structural features position it as a valuable tool for chemical biology probe development. Ongoing research at several institutions is exploring its use in activity-based protein profiling (ABPP) and fragment-based drug discovery. The combination of its synthetic accessibility and diverse reactivity profile suggests that 5-Chloro-6-Methylpyridine-2-sulfonyl Chloride will remain an important building block in pharmaceutical research for the foreseeable future.

• 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)
• 2680771-01-9(4-cyclopentyl-3-{(prop-2-en-1-yloxy)carbonylamino}butanoic acid)
• 2098070-20-1(2-(3-(Pyridin-3-yl)-1H-pyrazol-1-yl)acetimidamide)
• 1444113-98-7(N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide)
• 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)