• 1. Acentric and chiral heterometallic inorganic–organic hybrid frameworks mediated by alkali or alkaline earth ions: synthesis and NLO properties
  Huabin Zhang,Shaowu Du CrystEngComm, 2014,16, 4059-4068
• 2. An insight into the role of side chains in the microstructure and carrier mobility of high-performance conjugated polymers?
  Jianyao Huang,Dong Gao,Zhihui Chen,Weifeng Zhang Polym. Chem., 2021,12, 2471-2480
• 3. An Aptamer Bio-barCode (ABC) assay using SPR, RNase H, and probes with RNA and gold-nanorods for anti-cancer drug screening
  Chengbin Yang,Hing Lun Tsang,Pui Man Lau,Ken-Tye Yong,Ho Pui Ho,Siu Kai Kong Analyst, 2017,142, 3579-3587
• 4. An integrated microfluidic platform for sensitive and rapid detection of biological toxins?
  Robert J. Meagher,Anson V. Hatch,Ronald F. Renzi,Anup K. Singh Lab Chip, 2008,8, 2046-2053
• 5. Acenaphthenic hopanoids, a novel series of aromatised
  Teresita Carrillo-Hernández,Philippe Schaeffer,Pierre Albrecht Chem. Commun., 2001, 1976-1977

Research Briefing on 4-(4-Iodo-3-methyl-pyrazol-1-yl)-butyric acid (CAS: 1354705-25-1) in Chemical Biology and Pharmaceutical Applications

The compound 4-(4-Iodo-3-methyl-pyrazol-1-yl)-butyric acid (CAS: 1354705-25-1) has recently emerged as a key intermediate in medicinal chemistry and chemical biology research. This heterocyclic carboxylic acid derivative combines a pyrazole core with an aliphatic carboxylic acid chain, offering unique physicochemical properties that make it valuable for drug discovery and biochemical probe development. Recent studies highlight its role as a versatile building block for the synthesis of targeted kinase inhibitors and covalent protein modifiers.

Structural analysis reveals that the iodine atom at the 4-position of the pyrazole ring enables diverse cross-coupling reactions, while the carboxylic acid moiety facilitates conjugation to various scaffolds. The methyl group at the 3-position provides steric control in molecular interactions. This combination of features has led to increased utilization of 1354705-25-1 in fragment-based drug discovery programs, particularly for ATP-binding site targeting in protein kinases.

In a 2023 study published in the Journal of Medicinal Chemistry, researchers employed 4-(4-Iodo-3-methyl-pyrazol-1-yl)-butyric acid as a core structure for developing selective JAK3 inhibitors. The team demonstrated that modifications at the carboxylic acid position allowed for optimal interactions with the kinase's solvent-exposed region, achieving >100-fold selectivity over other JAK family members. The iodine atom served as a crucial handle for late-stage diversification through palladium-catalyzed cross-coupling reactions.

Another significant application appears in chemical biology probes, as reported in ACS Chemical Biology (2024). The compound was conjugated to photoaffinity labels and mass spectrometry tags to create activity-based probes for pyrazole-binding proteins. The study identified several previously unknown targets of this chemotype in cancer cell lysates, suggesting potential new therapeutic avenues. The moderate lipophilicity (calculated logP ~2.1) and good aqueous solubility (>10 mM at pH 7.4) of 1354705-25-1 contribute to its favorable probe characteristics.

Recent synthetic improvements have enhanced the accessibility of this compound. A 2024 Organic Process Research & Development paper described a streamlined synthesis route starting from 3-methyl-4-iodopyrazole, achieving an overall yield of 68% with excellent purity (>99% by HPLC). This advancement addresses previous supply chain challenges and supports broader investigation of this scaffold.

The safety profile of 4-(4-Iodo-3-methyl-pyrazol-1-yl)-butyric acid has been characterized in recent toxicology studies. While showing good stability under physiological conditions, researchers recommend handling precautions due to potential iodine-mediated reactivity. Proper storage conditions (2-8°C under inert atmosphere) have been established to maintain long-term stability.

Future research directions include exploration of this scaffold in PROTAC design (as the carboxylic acid can readily link to E3 ligase ligands) and further investigation of its inherent biological activity. Several pharmaceutical companies have included derivatives of 1354705-25-1 in their preclinical pipelines, particularly for inflammatory and oncological indications.

• 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)