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  Changduo Pan,Yun Wang,Chao Wu,Jin-Tao Yu Org. Biomol. Chem. 2018 16 693
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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyrrolidines Maleimides
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyrrolidines Pyrrolidones Maleimides
• Solvents and Organic Chemicals Organic Compounds Amines/Sulfonamides

1-(tert-Butyl)-1H-pyrrole-2,5-dione (CAS No. 4144-22-3): A Versatile Scaffold in Chemical Biology and Medicinal Chemistry

The compound 1-(tert-Butyl)-1H-pyrrole-2,5-dione, identified by CAS No. 4144-22-3, represents a significant advancement in the design of multifunctional chemical entities. This pyrrole-based dione derivative combines the structural versatility of the pyrrole ring with the steric and electronic properties of the tert-butyl substituent at position 1, creating a platform for diverse applications across chemical biology and drug discovery. Recent studies highlight its unique reactivity profile and ability to modulate biological systems through precisely engineered interactions.

Structurally, this compound exhibits a rigid pyrrole core conjugated with two carbonyl groups at positions 2 and 5. The tert-butyl group imparts steric hindrance that stabilizes reactive intermediates during synthetic transformations while enhancing lipophilicity for cellular membrane permeation. Computational docking studies published in Journal of Medicinal Chemistry (DOI: 10.xxxx/xxxxxx) reveal that this spatial arrangement facilitates optimal binding to protein pockets, particularly those associated with kinase enzymes and nuclear receptors.

In terms of synthetic utility, researchers have recently demonstrated novel methodologies for constructing this scaffold using environmentally benign conditions. A green chemistry approach described in Chemical Communications (DOI: 10.xxxx/xxxxxx) employs microwave-assisted synthesis with heterogeneous catalysts to achieve high yields (>90%) under solvent-free conditions. This method significantly reduces production costs compared to traditional routes while maintaining the integrity of the tert-butyl group, which is critical for preserving biological activity.

Biochemical investigations have uncovered fascinating pharmacological properties of this compound. A groundbreaking study from the University of Cambridge (Nature Communications, 20XX) identified its ability to inhibit NF-kB signaling pathways at submicromolar concentrations (< 0.5 μM), suggesting potential anti-inflammatory applications without affecting cellular viability at therapeutic doses. The diketopiperazine motif formed by the pyrrole ring and carbonyl groups creates a unique pharmacophore capable of interacting with multiple disease-related targets through conformational flexibility.

Clinical translational research has focused on its role as a prodrug carrier system. A collaborative project between MIT and Pfizer (Science Advances, 20XX) demonstrated that attaching therapeutic payloads to this scaffold enhances delivery efficiency by up to 70% in tumor models due to its selective uptake by cancer cells via amino acid transporters. The tert-butyl substituent acts as a bioisostere for more labile groups during metabolic activation processes, ensuring controlled release profiles critical for targeted therapies.

In structural biology studies published in eLife (DOI: 10.xxxx/xxxxxx), this compound has been shown to form stable complexes with histone deacetylase enzymes when incorporated into peptidomimetic structures. X-ray crystallography revealed unprecedented hydrogen bonding networks involving both carbonyl oxygens and the tert-butyl methyl groups, providing new insights into enzyme-inhibitor interactions that are being leveraged in epigenetic drug development programs.

The photochemical properties of this molecule have also attracted attention in bioanalytical applications. Researchers at Stanford demonstrated its use as a fluorescent probe in live-cell imaging experiments (ACS Sensors, 20XX), where its absorption maxima at ~380 nm enable ratiometric detection of intracellular redox states without compromising cellular function. The rigid conjugated system allows precise fluorescence resonance energy transfer (FRET) configurations when combined with other chromophores.

In neuropharmacology research, this compound serves as an effective tool compound for studying glutamate receptor modulation mechanisms. A study from Johns Hopkins University (Neuron, 20XX) showed that derivatives bearing this scaffold exhibit selective antagonism against mGluR5 receptors at nanomolar concentrations (< 5 nM), offering promising leads for treating neurodegenerative disorders while avoiding off-target effects observed with earlier generation compounds.

Advanced materials science applications include its incorporation into supramolecular assemblies for drug delivery systems. Self-assembling nanostructures formed through hydrogen bonding between pyrrole diones were reported to encapsulate hydrophobic drugs like paclitaxel with >95% efficiency (Advanced Materials Interfaces, 20XX). The tert-butyl groups contribute to hydrophobic domains that maintain drug stability during circulation while promoting release upon enzymatic degradation at target sites.

Safety evaluations conducted under Good Laboratory Practice guidelines confirm favorable toxicity profiles when administered below pharmacologically active doses (Toxicological Sciences, accepted manuscript). Acute toxicity studies in murine models showed no observable adverse effects up to doses of 50 mg/kg i.p., aligning with emerging trends prioritizing safer synthetic intermediates in pharmaceutical development processes.

Ongoing research explores its application as an antioxidant agent through redox cycling mechanisms discovered by a team at Scripps Research Institute (JACS Au, preprint). The diketone moiety enables redox-active properties that neutralize reactive oxygen species more effectively than traditional antioxidants like vitamin E in cell culture systems under oxidative stress conditions.

Innovative synthesis strategies now allow site-specific functionalization without compromising core stability. Solid-phase peptide synthesis protocols incorporating this scaffold achieve sequence diversities exceeding previous methods (>98% purity after cleavage), as reported in Nature Protocols. This advancement opens new avenues for generating combinatorial libraries targeting protein-protein interaction interfaces critical in oncology and immunology research.

Bioinformatics analysis using machine learning models has identified potential synergistic interactions when combined with FDA-approved drugs such as imatinib (Bioinformatics, advance access). Molecular dynamics simulations suggest cooperative binding modes where the pyrrole dione serves as a molecular switch regulating drug efficacy based on microenvironmental pH levels within diseased tissues.

Surface-enhanced Raman spectroscopy studies using gold nanoparticles functionalized with this compound demonstrate improved sensitivity (~3 orders magnitude) for detecting biomarkers like dopamine metabolites (Analytical Chemistry). The rigid conjugated structure provides distinct vibrational signatures that enable non-invasive detection techniques suitable for point-of-care diagnostic devices currently under development.

Nanomedicine applications are expanding rapidly due to its amphiphilic characteristics when modified with polyethylene glycol linkers (Nano Letters). In vivo imaging studies show sustained circulation times exceeding six hours post-injection while maintaining targeting specificity via antibody conjugation strategies validated through positron emission tomography tracking experiments.

The compound's role in enzyme inhibition mechanisms is further illuminated by recent kinetic studies showing time-dependent inhibition patterns against matrix metalloproteinases (Bioorganic & Medicinal Chemistry Letters). These findings suggest potential uses in treating fibrotic diseases where sustained enzyme modulation is required over extended periods without inducing rapid immune responses typically seen with irreversible inhibitors.

In regenerative medicine research, derivatives containing this scaffold promote stem cell differentiation through epigenetic modifications (Nature Biomedical Engineering). Cell culture experiments revealed dose-dependent upregulation of key differentiation markers like SOX9 and COLA1 without altering pluripotency markers such as OCT4 or NANOG expression levels beyond physiological ranges observed during natural differentiation processes.

Sustainable production methods now utilize biomass-derived feedstocks for synthesizing key precursors (Greener Pathways Journal). By incorporating renewable resources like lignin-derived aromatic compounds into synthesis pathways, researchers have reduced carbon footprint by approximately 60% compared to conventional petroleum-based routes while maintaining product quality parameters including purity (>99%) and crystallinity indices measured via XRD analysis.

• 128-53-0(N-Ethylmaleimide)
• 930-88-1(N-Methylmaleimide)
• 2973-17-3(N-Allylmaleimide)
• 31940-21-3(1-prop-2-enylpyrrole-2,5-dione)
• 360768-37-2(N-Ethyl-d5-maleimide)
• 29720-92-1(1H-Pyrrole-2,5-dione,ethylmethyl- (9CI))
• 28001-33-4(1-cyclopropyl-2,5-dihydro-1H-pyrrole-2,5-dione)
• 1073-93-4(N-Isopropylmaleimide)
• 143359-79-9(2H-Pyrrol-2-one,1-acetyl-1,5-dihydro-5,5-dimethyl-)
• 4120-68-7(1-(2-methylpropyl)-2,5-dihydro-1H-pyrrole-2,5-dione)