• 1. Fatty acid positional distribution in colostrum and mature milk of women living in Inner Mongolia, North Jiangsu and Guangxi of China?
  Long Deng,Qian Zou,Biao Liu,Wenhui Ye,Chengfei Zhuo,Li Chen,Ze-Yuan Deng,Ya-Wei Fan,Jing Li Food Funct., 2018,9, 4234-4245
• 2. Elusive 2-aminofuran Diels–Alder substrates for a straightforward synthesis of polysubstituted anilines?
  Ana G. Neo,Ana Bornadiego,Jesús Díaz,Stefano Marcaccini,Carlos F. Marcos Org. Biomol. Chem., 2013,11, 6546-6555
• 3. Estimation of fusel-oil in spirits
  Analyst, 1890,15, 203-209
• 4. Excited-state proton-coupled electron transfer within ion pairs?
  Gerald J. Meyer,Leif Hammarstr?m Chem. Sci., 2020,11, 3460-3473
• 5. Excimer formation effects and trap-assisted charge recombination loss channels in organic solar cells of perylene diimide dimer acceptors?
  Min Kim,Jae-Joon Lee,Tengling Ye,Panagiotis E. Keivanidis,Kilwon Cho J. Mater. Chem. C, 2020,8, 1686-1696

Research Briefing on 1-(Azidomethyl)-3,5-dimethylbenzene (CAS: 222716-36-1) in Chemical Biology and Pharmaceutical Applications

1-(Azidomethyl)-3,5-dimethylbenzene (CAS: 222716-36-1) is a specialized aromatic compound featuring an azidomethyl functional group, which has garnered significant attention in chemical biology and pharmaceutical research due to its versatile reactivity. This compound serves as a critical intermediate in click chemistry, bioconjugation, and drug discovery, particularly in the development of targeted therapies and diagnostic tools. Recent studies have explored its applications in photoaffinity labeling, proteomics, and the synthesis of novel bioactive molecules.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the utility of 1-(azidomethyl)-3,5-dimethylbenzene as a photo-crosslinking agent for mapping protein-ligand interactions. Researchers employed this compound to covalently capture transient binding events between small-molecule inhibitors and kinase targets, enabling structural insights into allosteric modulation. The azide group's photolytic properties allowed for precise spatiotemporal control, highlighting its advantages over traditional crosslinkers.

In drug discovery, 1-(azidomethyl)-3,5-dimethylbenzene has been utilized as a building block for PROTAC (Proteolysis Targeting Chimera) development. A 2024 Nature Chemical Biology paper reported its incorporation into heterobifunctional degraders targeting oncogenic proteins, where the compound's lipophilicity and metabolic stability improved cellular permeability compared to aliphatic azide analogs. Molecular dynamics simulations further revealed enhanced target engagement kinetics due to the aromatic scaffold's rigid geometry.

Ongoing clinical-stage research (Phase I/II trials) is investigating azide-containing antibody-drug conjugates (ADCs) incorporating derivatives of 1-(azidomethyl)-3,5-dimethylbenzene. The compound's bioorthogonal reactivity enables efficient payload attachment while maintaining antibody integrity, as evidenced by recent pharmacokinetic data showing >90% serum stability over 72 hours. This addresses a critical challenge in ADC development regarding linker robustness.

From a synthetic chemistry perspective, novel continuous-flow protocols have been developed for safer large-scale production of 1-(azidomethyl)-3,5-dimethylbenzene. A 2023 Organic Process Research & Development publication detailed a microreactor system that minimizes azide accumulation risks while achieving 92% yield at kilogram scale, representing a significant advancement over batch processes. This methodology is being adopted by several CDMOs for GMP manufacturing.

Emerging applications include the compound's use in DNA-encoded library (DEL) technology, where its click-compatibility enables efficient hit identification. A recent ACS Central Science report highlighted its role in generating DELs with enhanced structural diversity, particularly for challenging targets like protein-protein interfaces. The methyl-substituted benzene core was found to improve library member solubility in aqueous screening conditions.

Future research directions focus on expanding the compound's utility in live-cell imaging and theranostics. Preliminary data presented at the 2024 American Chemical Society meeting demonstrated successful incorporation into metabolic labeling probes for tracking tumor-associated glycans, with potential applications in intraoperative fluorescence guidance. Computational models suggest further optimization opportunities through halogenation of the aromatic ring to tune photophysical properties.

• 622-79-7(α-Azidotoluene)
• 102437-81-0(Benzene, 1,4-bis(azidomethyl)-)
• 126799-82-4(1-(azidomethyl)-3-methylbenzene)
• 17271-89-5(1-(Azidomethyl)-4-methylbenzene)
• 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)