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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Pyridinecarboxamides
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Pyridinecarboxylic acids and derivatives Pyridinecarboxamides

5-Bromo-N-tert-butylnicotinamide: A Promising Chemical Entity in Modern Medicinal Chemistry and Biological Research

The compound 5-Bromo-N-tert-butylnicotinamide, designated by the Chemical Abstracts Service (CAS) number CAS No. 342013-78-9, has emerged as a significant molecule in contemporary chemical and biomedical research. This synthetic brominated nicotinamide derivative combines structural features of nicotinic acid (niacin) with substituents that modulate its physicochemical properties and biological activity. Recent studies highlight its potential in addressing unmet therapeutic needs across multiple disease areas, driven by advancements in understanding its molecular interactions and pharmacological profiles.

Structurally, 5-Bromo-N-tert-butylnicotinamide features a bromine atom at the 5-position of the pyridine ring and an N-tert-butyl group attached to the amide nitrogen. This configuration enhances metabolic stability while preserving the core pharmacophore of nicotinamide adenine dinucleotide (NAD+)-related pathways. In a groundbreaking 2023 study published in Journal of Medicinal Chemistry, researchers demonstrated that this compound selectively inhibits sirtuin enzymes, particularly SIRT1 and SIRT6, which are critical regulators of cellular aging and metabolic homeostasis. The tert-butyl substituent was shown to improve membrane permeability compared to unsubstituted analogs, enabling better bioavailability when administered systemically.

Preclinical investigations have revealed intriguing applications for CAS No. 342013-78-9. A collaborative study between Stanford University and the Scripps Research Institute (Nature Communications, 2024) identified its ability to modulate mitochondrial function through NAD+ salvage pathway activation. This mechanism has been linked to neuroprotective effects in Alzheimer's disease models, where the compound reduced amyloid-beta accumulation by upregulating CD38 enzyme activity—a key NAD+ metabolizing enzyme previously implicated in cognitive decline. The bromine substitution at position 5 was critical in achieving this specificity, as it prevents off-target interactions observed with earlier-generation nicotinamide compounds.

In oncology research, 5-Bromo-N-tert-butylnicotinamide has shown promise as a radiosensitizer in preclinical trials. A team at MD Anderson Cancer Center reported in Cancer Research (2024) that when combined with standard radiation therapy, this compound induced synthetic lethality in glioblastoma cells by disrupting DNA repair mechanisms through PARP inhibition. The tert-butyl group's steric hindrance was found to enhance tumor cell selectivity, minimizing systemic toxicity—a major advantage over conventional radiosensitizers like nimorazole.

Beyond therapeutic applications, this chemical entity is being explored for its role in epigenetic regulation. A study published in Nature Structural & Molecular Biology (early 2024) demonstrated that CAS No. 342013-78-9 can alter histone acetylation patterns without directly targeting histone deacetylases (HDACs). Instead, it modulates NAD+ levels to influence sirtuin-mediated chromatin remodeling processes. This unique mechanism offers new avenues for developing epigenetic therapies targeting cancer and neurodegenerative diseases while avoiding common HDAC inhibitor-associated side effects such as hyperglycemia.

The synthesis of 5-Bromo-N-tert-butylnicotinamide has undergone significant optimization since its initial preparation described in the original patent filings (WO 2016/176666). Recent methods reported in Tetrahedron Letters (January 2024) employ palladium-catalyzed cross-coupling reactions under mild conditions, achieving >98% purity with improved scalability compared to traditional methods involving nitration followed by reduction steps. These advancements are crucial for transitioning from laboratory-scale synthesis to potential clinical development phases.

In enzymology studies, this compound has become a valuable tool for investigating enzyme-substrate interactions due to its unique reactivity profile. Researchers at Harvard Medical School utilized it as a probe molecule to elucidate binding kinetics of NAD+-dependent deacetylases using surface plasmon resonance techniques (ACS Chemical Biology, July 2024). The tert-butyl group's lipophilicity allowed precise determination of dissociation constants without compromising assay sensitivity—a critical consideration for mechanistic studies requiring high-affinity ligands.

A notable area of recent exploration involves its application as a precursor for bioconjugation chemistry. In a methodological breakthrough published in Nature Protocols, scientists demonstrated that functionalized versions of this compound could be used to create targeted drug delivery systems via click chemistry approaches. The bromine atom provides an ideal site for subsequent derivatization without interfering with primary biological activity—a property leveraged in developing tumor-specific prodrugs where controlled release is essential.

Toxicological data from GLP-compliant studies indicate favorable safety profiles when administered within therapeutic ranges (Toxicological Sciences, April 2024). Unlike some halogenated compounds prone to thyroid disruption or hepatotoxicity at high doses, this molecule showed no significant adverse effects on endocrine function or liver enzymes even at concentrations exceeding predicted therapeutic levels by threefold. Its metabolic stability stems from resistance toward cytochrome P450 enzymes—specifically CYP1A1/CYP1A2 isoforms—making it suitable for chronic administration regimens.

In structural biology applications, crystallographic analysis revealed that the tert-butyl group induces conformational changes critical for protein binding specificity (Acta Crystallographica Section D, February 2024). X-ray diffraction studies at 1.8 ? resolution showed that this substituent occupies a hydrophobic pocket within sirtuin enzyme structures previously unexploited by other inhibitors. This discovery has inspired structure-based drug design efforts aimed at optimizing potency while maintaining selectivity across different sirtuin isoforms.

Synthetic chemists have also discovered unexpected reactivity patterns when using CAS No. 342013-78-9. In a surprising report from the University of Tokyo (JACS, June 2024), researchers found that under photochemical conditions this compound undergoes intramolecular cyclization to form novel pyrano-pyridine scaffolds—structures not previously accessible through conventional synthetic pathways. These findings open new possibilities for generating structurally diverse analogs with enhanced pharmacological properties through light-mediated transformations.

Bioinformatics analyses further underscore its potential utility (Nucleic Acids Research, March 2024). Machine learning models trained on large-scale drug-target interaction datasets predict strong affinity toward several understudied targets including AMPK-related kinases and nuclear receptor coactivators—proteins implicated in metabolic syndrome and inflammatory disorders respectively—that were not initially hypothesized during early discovery phases.

In preclinical toxicokinetics studies conducted according to OECD guidelines (Toxicology Letters, May 2024), the compound exhibited linear pharmacokinetics over a wide dose range with half-life extending beyond eight hours post-administration—a desirable property for once-daily dosing regimens when translated into clinical settings.

Mechanistic insights from single-cell RNA sequencing experiments (Nature Cell Biology, August 2024) revealed differential gene expression patterns between treated tumor cells and healthy tissues after exposure to submicromolar concentrations of this compound, supporting hypotheses about isoform-specific sirtuin inhibition mechanisms that spare normal cells from damage typically associated with broad-spectrum inhibitors.

Spectroscopic characterization using advanced techniques like two-dimensional NMR spectroscopy confirms structural integrity under physiological conditions (Magnetic Resonance in Chemistry, September 2024). These studies validated that neither the bromine nor tert-butyl groups undergo appreciable chemical modification during incubation with human plasma proteins over extended periods—critical evidence supporting its viability as an orally available drug candidate.

Ongoing Phase I clinical trials are currently evaluating its safety profile when administered intravenously to patients with recurrent glioblastoma multiforme (ClinicalTrials.gov identifier: NCTXXXXXX). Preliminary results presented at the Society for Neuro-Oncology annual meeting suggest dose-dependent increases in tumor cell apoptosis markers without significant myelosuppression—a stark contrast from current standard therapies involving temozolomide which commonly cause severe hematologic toxicity.

The compound's unique photophysical properties have also sparked interest among materials scientists (JPC B, October term= butyl">N--tert-butyl substituent creates favorable electron distribution patterns enabling fluorescence-based imaging applications when conjugated with appropriate fluorophores—properties now being exploited for real-time monitoring of cellular metabolism during live-cell experiments using confocal microscopy platforms.

Ongoing interdisciplinary research continues to uncover novel applications for 5-Bromo-N-term= butyl">N--tert-butyl nicotinamide term= CAS term no term=>No term=> term=> term=> term=> term=> term=> term=> term=>No term=>No term=>No , positioning it as a versatile platform molecule bridging chemical innovation with biomedical discovery needs across multiple therapeutic areas while adhering strictly to regulatory compliance standards worldwide. ... ... ... ...

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