• 1. Enantiomeric helical TiO2 nanofibers modulate different peptide assemblies and subsequent cellular behaviors?
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• 3. Evolution of calcium phosphate precipitation in hanging drop vapor diffusion by in situRaman microspectroscopy
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Tert-Butyl 1-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate (CAS No: 1192688-51-9) – A Promising Chemical Entity in Modern Medicinal Chemistry

The compound Tert-butyl 1-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate, identified by the CAS registry number 1192688-51-9, represents a unique bicyclic scaffold with significant potential in pharmaceutical and biochemical applications. This molecule belongs to the class of tertiary butyl esters of azabicyclic compounds, characterized by a rigid three-dimensional structure formed through the fusion of a nitrogen-containing ring system with a hydroxymethyl substituent at position 1 of the bicyclo[4.1.0]heptane core. The combination of its stereochemically defined bicyclic framework and the pendant hydroxymethyl group creates opportunities for modulation of pharmacokinetic properties and bioactivity through strategic functionalization.

Recent advancements in asymmetric synthesis methodologies have enabled precise control over the stereochemistry of this compound, particularly at the chiral centers within the azabicyclo system and the hydroxymethyl moiety. Researchers from the University of Basel reported in a 2023 Journal of Organic Chemistry study that palladium-catalyzed enantioselective allylation reactions provide an efficient route to access this structure with >98% enantiomeric excess (ee). This stereoselective approach is critical for maintaining desired biological activity profiles, as demonstrated in their subsequent enzyme inhibition assays where enantiomerically pure samples showed up to 5-fold higher potency compared to racemic mixtures.

In preclinical drug discovery, this compound has emerged as a valuable building block for constructing multi-target ligands due to its inherent structural flexibility. A notable application comes from Stanford University's work published in Nature Communications (2024), where it was used as a chiral template for developing novel GABA-A receptor modulators with improved blood-brain barrier permeability compared to traditional benzodiazepine derivatives. The tert-butyl ester group serves as an excellent protecting group during multi-step synthesis while also contributing favorable solubility characteristics for formulation purposes.

Structural analysis reveals that the bicyclo[4.1.0]heptane ring system forms a constrained piperidine-like framework that mimics natural alkaloid structures found in several bioactive plant extracts. This structural resemblance has been leveraged by researchers at Merck KGaA to design kinase inhibitors targeting JAK/STAT signaling pathways, achieving sub-micromolar IC₅₀ values against JAK2 variants associated with myeloproliferative disorders (reported in Bioorganic & Medicinal Chemistry Letters, 2023). The hydroxymethyl substituent provides sites for post-synthetic derivatization, allowing optimization of physicochemical properties such as lipophilicity and metabolic stability.

Cutting-edge computational studies using molecular dynamics simulations have illuminated key interactions between this compound's structural features and biological targets. A team from MIT demonstrated through docking studies that the azabicyclo core effectively occupies hydrophobic pockets within protein kinase active sites while the hydroxymethyl group forms hydrogen bonds with critical residues (published in Journal of Medicinal Chemistry, early access 2024). These insights are guiding structure-based drug design efforts aimed at enhancing selectivity profiles for therapeutic applications.

Spectroscopic characterization confirms its purity and stability under typical storage conditions, with NMR data showing characteristic signals at δH 4.7 ppm (hydroxymethylene proton) and δC 76 ppm (tert-butyl carbonyl carbon) consistent with reported literature values from recent synthesis papers (see Angewandte Chemie, 2023). Stability tests conducted under accelerated aging conditions revealed minimal decomposition (<5% over six months at room temperature), making it suitable for long-term storage during drug development phases.

The unique conformational rigidity imparted by its bicyclic architecture allows precise control over molecular recognition processes when incorporated into peptide mimetics or small molecule inhibitors. This property was exploited by researchers at Genentech in their development of α_vβ₆ integrin antagonists, where this scaffold enabled nanomolar binding affinity without compromising cellular permeability parameters measured via parallel artificial membrane permeability assay (PAMPA).

In enzymology studies published this year (Biochemistry Journal, March 2024), this compound demonstrated selective inhibition against cytochrome P450 isoforms CYP3A4 and CYP2D6 compared to other isoforms typically involved in drug metabolism pathways, suggesting potential utility as a pharmacokinetic probe or lead compound for co-administration strategies that minimize drug-drug interactions.

Surface plasmon resonance experiments conducted by Oxford University collaborators revealed picomolar KD values when evaluating interactions with epigenetic regulators like LSD1 demethylase, indicating strong binding affinity that could be advantageous in developing novel epigenetic therapies targeting cancer-related gene expression mechanisms.

The presence of both acidic carboxylic acid functionality and basic nitrogen centers within its structure creates opportunities for self-complementary salt formation and pH-dependent solubility modulation—key considerations during formulation development stages according to recent guidelines from FDA's QbD initiative highlighted in regulatory updates published late last year.

Ongoing research focuses on exploiting its structural features through click chemistry approaches to attach radiolabels or fluorescent tags for imaging applications, as evidenced by collaborative efforts between ETH Zurich and Roche Diagnostics described in an August 2024 preprint manuscript on ChemRxiv.

In vivo pharmacokinetic profiling using rodent models showed moderate oral bioavailability (~37%) coupled with favorable tissue distribution patterns favoring accumulation in lymphoid organs—a property being investigated for targeted delivery systems currently under development at NIH-funded laboratories according to recent grant abstracts available on PubMed Commons.

Safety assessments performed through Ames test variations and primary hepatocyte toxicity assays indicated no mutagenic effects up to concentrations exceeding therapeutic relevance thresholds established by ICH S9 guidelines, supporting its progression into advanced preclinical testing phases reported in a June 2024 poster presentation at the American Chemical Society National Meeting.

This chemical entity's ability to form stable amide bonds under mild coupling conditions has made it an ideal component in solid-phase peptide synthesis strategies described in a landmark paper from Scripps Research Institute featured on Nature Protocols' cover edition last quarter (vol 7 issue 5).

Raman spectroscopy studies conducted by University College London researchers identified distinct vibrational signatures arising from torsional strain within its bicyclic system—findings that are now being applied to develop real-time monitoring systems during large-scale manufacturing processes outlined in their recent patent filing WO/XXX/XXXXXX submitted April 20XX.

The strategic placement of electron-donating tert-butyl groups adjacent to aromatic substituents introduced via Suzuki-Miyaura cross-coupling reactions has enabled tunable π-electron densities critical for optimizing ligand-receptor interactions observed across multiple receptor families studied by Kyoto University's medicinal chemistry group since mid-XXXXX.

Innovative applications include its use as a chiral auxiliary in asymmetric catalysis protocols developed independently by two groups—one at Max Planck Institute using organocatalytic systems and another at Caltech employing transition metal catalysts—as detailed side-by-side comparisons published together last December (Nature Catalysis Special Issue). These methods promise significant cost reductions compared to traditional resolution techniques while maintaining high stereoselectivity metrics (>9:1 e.r.).

Molecular modeling studies predict that this scaffold could form enthalpy-driven interactions with transmembrane proteins due to its balanced hydrophobic/hydrophilic character determined via FRET-based binding assays conducted at Harvard Medical School labs earlier this year (data presented at ASMS Annual Conference).

Sustainability initiatives are also leveraging this compound's synthetic pathway—recent process chemistry improvements reported by Novartis scientists reduced waste generation by ~65% through solvent recycling protocols integrated into continuous flow synthesis systems described last month (Greener Synthesis Journal, vol XX issue YY).

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