Afatinib N-Oxide , CAS No.2413212-11-8

CAS: 2413212-11-8 Cat. No.: A1443922 Fórmula: C₂₄H₂₅ClFN₅O₄ Peso molecular: 501.94

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Visão geral

Afatinib N-Oxide is an impurity of Afatinib dimaleate in oxidative degradation. Afatinib dimaleate is an irreversible EGFR family inhibitor.

Specifications

Condições de armazenamento de armazenamento

Store at -20°C

Enviado em

Ice chest + Ice pads

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Nomes e identificadores

Peso molecular

501.94

Application Protocols

Not specified for this item; no tested application protocols are provided. For general use as an analytical reference standard, researchers often prepare DMSO stock solutions and analyze by LC–MS/MS; however, exact protocols (e.g., instrument settings, dilutions) should be established and validated in-house.

Biological Roles

Context (literature/general; no clinical claims)

• Afatinib is a well-characterized small-molecule kinase inhibitor scaffold targeting the ErbB family in biochemical systems. The N-oxide analog is commonly explored as an oxidative derivative/metabolite in metabolism studies.
• N-oxidation of tertiary amines can alter physicochemical properties (basicity, polarity, permeability) and thereby modulate biochemical potency and selectivity in target engagement assays.
• In vitro, N-oxide forms may show differences in covalent reactivity toward nucleophiles (e.g., cysteine residues) due to altered electron distribution and solvation around the acrylamide warhead and neighboring amine.
• In ADME research, the N-oxide can serve as a surrogate or authentic standard to quantify oxidative biotransformation pathways and to validate bioanalytical methods (e.g., microsome/S9 fraction incubations, hepatocyte assays).

Use in experimental biology

• Tool compound to benchmark cellular uptake/efflux changes vs. the parent, aiding studies on transporter involvement and passive permeability.
• Reference for evaluating redox interconversion potential under cellular conditions and assessing artifact formation during sample workup.

Note: Specific potency, selectivity, or kinetic constants for Afatinib N-Oxide are not provided here and should be obtained from primary literature or determined experimentally.

Buffer Applications

Not typically applicable. Afatinib N-Oxide is a small organic molecule and not used as a buffering agent. For experimental work, select assay buffers based on your biological system and solubility constraints, and introduce the compound via a co-solvent (e.g., DMSO) at a low final percentage to avoid buffer perturbation.

Green Alternatives

While Afatinib N-Oxide itself has no direct “green” substitute, greener choices can be applied to its handling and analytics.

Greener solvent choices (general guidance)

• Prefer DMSO over DMF/NMP when feasible due to a more favorable safety profile.
• Use ethanol or isopropanol for low-concentration dilutions when compatible, instead of methanol or chlorinated solvents.
• For chromatography, minimize acetonitrile consumption via method optimization (shorter columns, core–shell particles) or partially substitute with methanol when resolution permits.

Comparison (illustrative, general)

• DMSO: strong solvency, water-miscible, higher boiling point; greener than DMF/NMP but can have disposal considerations.
• DMF/NMP: powerful solvents but reproductive-toxicity concerns; avoid unless required for dissolution.
• Ethanol: renewable and lower toxicity; may have limited solvency for highly lipophilic solids at high concentrations.

Operational measures

• Scale down assays to microliter volumes; adopt UHPLC to cut solvent use.
• Implement solvent recycling for ACN/MeOH where permitted and validated.

Pharmaceutical Uses

No therapeutic or clinical uses are claimed for this catalog item. Typical roles in pharmaceutical research/development (general; no clinical claims):

• Analytical reference standard for method development and validation (e.g., LC–MS/MS) to monitor oxidative derivatives of afatinib in discovery and DMPK workflows.
• Stability-indicating methods: stress-testing control for oxidative pathways and to establish specificity of impurity profiling.
• Metabolite identification support: aids spectral library building and retention-time locking in bioanalytical assays.

Regulatory/compendial status

• No pharmacopeial monograph is indicated for this item. Any use in regulated studies should be supported by an internal qualification package (identity, purity, stability) per your quality system.

Formulation context

• If used in preclinical formulations for research, the compound is typically handled as a DMSO stock and diluted into vehicle systems; exact excipient systems and specifications are not provided for this item.

Physical Properties

Item-specific physical data

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Typical/indicative properties for this compound class (literature/general; not item specifications)

• State at ambient conditions: typically a solid for afatinib analogs.
• Solubility tendencies: poor aqueous solubility; good solubility in polar aprotic organic solvents (e.g., DMSO, DMF, NMP) is common for kinase inhibitor analogs. Exact solubility for this item is not specified; verify experimentally.
• LogP/logD: afatinib analogs are generally lipophilic; exact values for the N-oxide analog are not provided here.
• UV-vis: quinazoline chromophores often show strong UV absorption in the 250–350 nm region; precise maxima for this item are not specified.
• Melting point, boiling point, density, refractive index, pKa: Not specified for this item; refer to CoA/Spec Sheet or measure under your conditions.

Practical notes (general)

• Prepare concentrated stocks in dry DMSO and dilute into assay buffers immediately before use to mitigate precipitation. Confirm stability and solubility for your system by small-scale tests.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research use note: For research use only (not for human or veterinary use).

What grade means in practice (general guidance)

• Small-molecule screening library items are typically provided at high chemical purity suitable for discovery biology, mechanistic enzymology, and analytical reference use. Absence of explicit UV-cutoff/trace-metal/peroxide limits indicates these are not solvent-grade specifications but rather organic solid compound specs.
• If a stabilizer is present, it will be listed on the CoA; none is specified for this item.

Recommended quality checks (practitioner tips)

• Verify identity and purity in-house when critical: orthogonal methods such as LC–MS (single-ion monitoring for the [M+H]+ of the N-oxide), 1H/13C NMR, and HRMS.
• Monitor for potential interconversion between N-oxide and parent amine under harsh reducing conditions; include stress tests if method development requires it.
• For bioassays, confirm endotoxin is not relevant; this is a small molecule, not a biopolymer.

Reaction and Applications

This compound is not typically used as a synthetic reagent; its primary value is as a research/reference small molecule.

Research applications (general; literature/practice)

• Analytical reference standard: supports development of LC–MS/MS methods to differentiate parent afatinib from its N-oxide metabolite/analog in metabolic stability, microsomal incubations, and PK sample analysis.
• Mechanistic studies: enables probing of the impact of amine oxidation on target engagement, reactivity toward cysteine residues (Michael acceptor), and physicochemical changes relative to afatinib.
• Stability studies: suitable for stress-testing (acid/base, redox, thermal, photolysis) to map interconversion pathways between amine and N-oxide forms and to build stability-indicating analytical methods.
• Assay controls: negative/positive control in biochemical or cellular assays where redox state of the amine influences activity; ensures assay specificity and detection linearity.

Practical tips

• Prepare fresh DMSO stocks; verify solubility by visual inspection and analytical confirmation. If precipitation occurs upon aqueous dilution, increase dilution steps or reduce final concentration.
• For LC–MS, optimize source conditions to minimize in-source reduction of N-oxides; softer ionization and appropriate mobile phase modifiers (e.g., 0.1% formic acid) can improve spectral fidelity.

Reaction Conditions

This item is not offered as a reagent for preparative reactions; typical “reaction conditions” are therefore not directly applicable.

General literature guidance relevant to handling and analysis (not item specifications)

• Stock solutions: dissolve in dry DMSO (e.g., 10–50 mM), vortex and, if needed, sonicate briefly; filter through 0.22 µm PTFE prior to analytical injection.
• LC–MS analysis: reversed-phase C18; mobile phases such as water + 0.1% formic acid (A) and acetonitrile + 0.1% formic acid (B); gradient methods commonly achieve baseline resolution between parent and N-oxide. Optimize source parameters to avoid in-source redox artifacts.
• Chemical stability screens: evaluate under acid (0.1–1 M HCl), base (0.1–1 M NaOH), oxidative (e.g., H2O2), thermal, and photolytic stress for stability-indicating methods. The N-oxide may revert under strong reducing conditions (e.g., PPh3, Zn/AcOH) in synthetic contexts.

If using in biochemical assays

• Keep final DMSO below assay tolerance (often ≤0.5–1% v/v). Pre-clear precipitates by centrifugation. Confirm concentration by UV/LC–MS quantitation.

Safety and Handling

GHS/SDS

• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• GHS classification/pictograms: Not specified for this item; refer to SDS.

General laboratory precautions (advisory)

• Handle in a chemical fume hood with appropriate PPE: lab coat, safety glasses, and suitable gloves (e.g., nitrile). Avoid inhalation of dust or aerosols and contact with skin or eyes.
• Avoid incompatibilities typical for organic amides/amines: strong oxidizers, strong acids/bases, and reactive acylating/alkylating agents. The N-oxide functionality can be sensitive to strong reducing agents; avoid uncontrolled reductions unless intended.
• Prevent contamination of water sources; dispose of waste via approved organic hazardous waste streams.

First aid (overview; defer to SDS)

• Inhalation: move to fresh air; seek medical attention if symptoms persist.
• Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing; seek medical advice if irritation persists.
• Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

Special risks and stability (general)

• Protect from prolonged light and moisture. Store cold per item guidance. When preparing DMSO stocks, minimize repeated freeze–thaw cycles by aliquoting.
• Always consult the official SDS for authoritative hazard and response information.

Solvent Selection

Applicability: This section addresses dissolving and handling Afatinib N-Oxide as a research small molecule standard.

General solvent guidance (literature/practice; not item specifications)

• Primary stock solvent: DMSO is commonly preferred due to high solvating power for lipophilic kinase inhibitor analogs.
• Alternative strong solvents: DMF, NMP, or mixtures with acetonitrile or methanol can aid dissolution. Water miscibility of DMSO enables convenient buffer dilution.
• Aqueous buffers: direct dissolution into water or PBS is typically poor; instead, prepare a DMSO concentrate (e.g., 10–50 mM) and dilute to final organic content ≤0.5–1% v/v as tolerated by the assay.

Polarity and miscibility (general)

• Expected behavior: relatively non-volatile, polar-aprotic–soluble, sparingly water-soluble. Co-solvent systems (ACN/water with 0.1% formic acid or ammonium formate) are suitable for LC–MS sample preparation.

Comparison (general considerations)

• DMSO vs DMF: DMSO offers lower toxicity profile and easier handling; DMF can improve solubility for very recalcitrant samples but is less desirable from an EH&S standpoint.
• MeOH/ACN: good for analytical dilutions and LC compatibility but may not fully dissolve solid at high concentrations without a stronger primary solvent.

Storage and Reconstitution

• Storage conditions (item-specific): Store at -20°C.
• Shipping: Ice chest + ice pads (cold-pack shipment) as provided.
• Reconstitution: Not specified for this item; refer to CoA/Spec Sheet.

General best practices (advisory)

• Upon receipt, allow the sealed container to equilibrate to room temperature before opening to minimize moisture condensation.
• If solid: divide into single-use aliquots under dry conditions (e.g., glovebox or desiccated environment) when feasible. If solution: aliquot and store at -20°C.
• Prepare concentrated stocks in dry DMSO; aliquot to avoid repeated freeze–thaw cycles. Protect from light and moisture.
• Stability: absent item-specific data, assess stability by periodic LC–MS or HPLC checks of stored aliquots. Always refer to the CoA for any stated retest dates or stability notes.

Structure and Identity

• Product name: Afatinib N-Oxide (SKU: A1443922)
• CAS: 2413212-11-8
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

General structural notes (literature/context):

• Afatinib is a 4-anilino-substituted quinazolinyl acrylamide bearing halogen and dimethylamino substituents. The “N-oxide” designation typically denotes oxidation of a tertiary amine or ring N to the corresponding N→O oxide in related analogs. For Afatinib N-oxide, the exact site of oxidation should be confirmed on the CoA/Spec Sheet or primary literature for this CAS.
• Functional group features expected for this class (literature): aromatic heterocycle(s), acrylamide Michael acceptor, anilide linkage, tertiary amine/N-oxide functionality, and halogen substituent(s).
• Stereochemistry: compounds in this class are commonly achiral; verify on the CoA/Spec Sheet for this exact item.

2D structure description (general):

• A fused bicyclic heteroaromatic core (quinazolinone/quinazoline-type) para-substituted by an anilide that extends to an acrylamide motif; a dialkylamino side chain is present and, in the N-oxide, bears an N→O bond (site to be verified).

Synthetic Utility

Afatinib N-Oxide is generally a target molecule/reference standard rather than a synthetic building block.

Contextual synthetic relevance (general)

• Oxidation state probe: comparison of the parent tertiary amine vs. its N-oxide informs SAR, reactivity, and ADME properties without modifying the core scaffold extensively.
• Method development: serves as a test substrate for selective N-oxidation or N-oxide reduction methodologies under mild conditions (e.g., peracids, dioxirane, or catalytic oxidations; P(III)-mediated reductions). These are literature concepts and not item-specific procedures.
• Analytical derivatization: N-oxides can display distinct chromatographic/ionization behavior, facilitating separation and detection when building impurity profiles for complex kinase inhibitor scaffolds.

Retrosynthetic considerations (general)

• Access commonly proceeds from the parent afatinib via controlled oxidation at the designated nitrogen center. Protecting-group strategies and chemoselectivity are crucial to avoid over-oxidation or undesired functionalization of the acrylamide.

Target Specificity

Not specified for this item; refer to CoA/Spec Sheet. Note: While afatinib scaffolds are widely studied against ErbB-family kinases in biochemical research, no target specificity data are provided here for the N-oxide analog.