Regorafenib-d3 - ≥98% , CAS No.1255386-16-3

CAS: 1255386-16-3 Cat. No.: R646852 분자식: C₂₁H₁₂D₃ClF₄N₄O₃ 분자량: 485.83 PubChem CID: 49822400

등급 & 순도 ≥98%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

개요

Regorafenib-d 3 is a deuterium labeled Regorafenib. Regorafenib is a multi-targeted receptor tyrosine kinase inhibitor.

Form:Solid

사양

사양 및 순도

≥98%

생화학 및 생리적 메커니즘

Regorafenib-d 3 is a deuterium labeled Regorafenib. Regorafenib is a multi-targeted receptor tyrosine kinase inhibitor.

보관 조건

Store at -20°C

배송

Ice chest + Ice pads

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순수함

≥98%

이름과 식별자

정식 스마일

CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F

IUPAC Name

4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-(trideuteriomethyl)pyridine-2-carboxamide

InChIKey

FNHKPVJBJVTLMP-FIBGUPNXSA-N

INCHI

1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)/i1D3

이성체 SMILES

[2H]C([2H])([2H])NC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F

PubChem CID

49822400

분자량

485.83

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • 분류 Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• 분류: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diarylethers
• Alternative Parents: N-phenylureas Trifluoromethylbenzenes Pyridinecarboxamides 2-heteroaryl carboxamides Phenol ethers Phenoxy compounds Fluorobenzenes Chlorobenzenes Aryl fluorides Aryl chlorides Heteroaromatic compounds Ureas Secondary carboxylic acid amides Azacyclic compounds Organonitrogen compounds Organofluorides Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds Alkyl fluorides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Diaryl ether - N-phenylurea - Trifluoromethylbenzene - Pyridinecarboxamide - Pyridine carboxylic acid or derivatives - 2-heteroaryl carboxamide - Phenoxy compound - Phenol ether - Halobenzene - Fluorobenzene - Chlorobenzene - Aryl chloride - Pyridine - Aryl halide - Monocyclic benzene moiety - Benzenoid - Aryl fluoride - Heteroaromatic compound - Carboxamide group - Urea - Secondary carboxylic acid amide - Organoheterocyclic compound - Carboxylic acid derivative - Azacycle - Organonitrogen compound - Alkyl halide - Alkyl fluoride - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organic nitrogen compound - Organofluoride - Organohalogen compound - Organochloride - Aromatic heteromonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

화학 및 물리적 특성

• 분자량: 485.800 g/mol
• XLogP3: 4.200
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 485.096 Da
• Monoisotopic Mass: 485.096 Da
• Topological Polar Surface Area: 92.400 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 686.000
• Isotope Atom Count: 3
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No vendor-tested biological application protocols (e.g., WB, IHC, IF, FC) are applicable to this small-molecule standard. The following generalized analytical protocol outlines typical use as an LC–MS/MS internal standard. Adjust to your SOPs and validate accordingly.

Example LC–MS/MS internal standard workflow (general):

1. Stock preparation: Dissolve regorafenib‑d3 in DMSO at 1–10 mM. Aliquot and store at −20°C.
2. Working IS solution: Dilute stock into acetonitrile (or ACN:water 50:50) to a convenient concentration (e.g., 100–1000 ng/mL), ensuring the same solvent composition is used for calibrators and QCs.
3. Sample preparation: Spike a fixed volume of IS into plasma or matrix before protein precipitation (3–4× volume ACN), vortex, centrifuge, and transfer supernatant. Alternatively, apply to SPE with water-wettable RP cartridges; elute with ACN.
4. LC–MS/MS: Inject onto C18 column; use water/0.1% formic acid and ACN/0.1% formic acid gradient. Monitor MRM transitions separated by +3 Da for IS vs analyte.
5. Quantitation: Construct calibration curves with analyte/IS response ratios; include low/medium/high QCs and evaluate recovery, matrix factor, and carryover.

Note: Exact concentrations, transitions, and retention times are method-dependent and must be established during method development. Refer to CoA for any item-specific guidance.

Biological Roles

Item-specific biological activity data are not provided for this product. As a deuterated analog intended primarily as an internal standard, regorafenib‑d3 is not supplied for pharmacology or cellular studies. The following is general, literature-based context on the unlabeled parent compound to inform analytical targeting; it should not be construed as a property claim for this item.

• Parent target classes (literature): Multikinase inhibitor activity has been reported for regorafenib against receptor tyrosine kinases (e.g., VEGFR family, PDGFR) and serine/threonine kinases (e.g., RAF isoforms). These interactions motivate its monitoring in biological matrices.
• Analytical relevance: Because the parent is lipophilic, extensively protein-bound, and may form multiple oxidative and conjugative metabolites, a stable isotope–labeled internal standard aids in accurate quantification in plasma, tissue, and formulation matrices.
• Isotopic substitution: Deuteration by three mass units preserves the parent’s chemical connectivity and chromatographic behavior; any kinetic isotope effects on biotransformation are generally minimal at analytical spike levels and are not relied upon for biological modulation.

Use limitations:

• This product is designated For research use only and is intended for laboratory analytical workflows. It is not for use in humans or animals, and no biological performance or potency is claimed or implied for this item.

Buffer Applications

This product is a hydrophobic small-molecule analytical standard rather than a buffering reagent. It does not form a defined conjugate acid/base pair suitable for pH control, and therefore it is not used to prepare biological or analytical buffers.

Practical notes relevant to buffers in analytical workflows:

• When spiking into aqueous buffers (e.g., LC mobile phases, enzyme incubation media), prepare concentrated stocks in DMSO or acetonitrile and dilute to a low final organic percentage (typically ≤1% v/v) to avoid precipitation and to maintain chromatographic performance.
• Avoid surfactants or ion-pairing reagents unless validated for the assay, as these can alter ionization efficiency in LC–MS/MS.
• Maintain consistent buffer composition (salt type, pH, organic content) between calibration standards, QCs, and study samples to ensure stable internal standard response.

Item-specific buffer-related specifications (pH stability ranges, solubility limits): Not specified for this item; refer to CoA/Spec Sheet for any additional guidance provided with the lot.

Green Alternatives

As an isotopically labeled reference standard, regorafenib‑d3 has no direct “green substitute” for its analytical role. However, greener practices can be adopted in its use and handling.

Greener practice considerations (general):

• Solvent selection: Prefer acetonitrile/water over chlorinated solvents for sample prep when compatible with recovery and stability. DMSO is acceptable for concentrated stocks; minimize volume in final injections to reduce viscosity and ESI suppression.
• Miniaturization: Use microextraction (e.g., µSPE, SPME) and 96-well low-volume workflows to cut solvent waste and sample consumption.
• Waste management: Segregate halogenated and non-halogenated waste; employ solvent recycling for ACN where facility permits.
• Energy: Store at −20°C as required, but batch analytical runs to reduce freezer door-open frequency; consolidate shipping with other cold-chain items to reduce packaging waste.

Comparison (process choices, general):

• Protein precipitation: ACN or MeOH; ACN often provides cleaner extracts and is more amenable to recovery/recycling. MeOH is less toxic but may co-precipitate differently; validate based on matrix.
• SPE vs LLE: SPE typically uses less solvent and can be automated; choose water-wettable reversed-phase cartridges to reduce chlorinated solvent use.

Note: No material substitution can replicate the mass-labeling function of the d3 analog; the greener approach focuses on solvent and workflow optimization rather than replacing the standard itself.

Pharmaceutical Uses

No excipient role, pharmacopeial monograph, or formulation grade is specified for this item. This product is supplied For research use only.

Relevant research/industrial contexts (non-clinical, non-therapeutic):

• Bioanalytical method development: Used as a stable isotope–labeled internal standard for quantitative determination of the parent compound in preclinical samples, in-process controls, and stability studies.
• Manufacturing support analytics: May be used to track API carryover, cleaning validation residues, or to validate extraction efficiency in complex matrices.
• Reference standard qualification: In regulated environments, lot-specific characterization (purity, isotopic distribution, water/residual solvents) should be recorded as part of method validation documentation, but no pharmacopeial status is implied by this listing.

Do not use this product for therapeutic, diagnostic, or clinical purposes. It is not approved as a drug substance, excipient, or clinical reference standard.

Physical Properties

Item-specific physicochemical specifications are not provided for this catalog entry. Where helpful, general/literature information on the parent compound is summarized for context. Do not treat literature values as specifications for this lot.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (exact, d3): Not specified for this item; refer to CoA/Spec Sheet. (Literature expectation: parent regorafenib ~482.8 g/mol; d3 analog typically ~+3.0 Da.)
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item. (Literature, parent: high-melting solid; exact value varies by form/polymorph.)
• Boiling point: Not applicable (decomposes before boiling; literature/general for polyaromatic ureas).
• Density: Not specified for this item.
• pKa: Not specified for this item. (Literature, parent: weakly basic/neutral; urea NHs not appreciably ionizing in water.)
• logP/logD: Not specified for this item. (Literature, parent: lipophilic, high logP.)
• Solubility: Not specified for this item. Practical guidance (general):
  • Sparingly soluble in water/buffers; readily soluble in polar aprotic organic solvents such as DMSO and DMF; soluble to moderate in dichloromethane and acetonitrile; limited in alcohols depending on conditions.
• UV-Vis: Not specified for this item. (Literature, parent: strong aromatic absorption in UV range.)

Note: For quantitative applications (e.g., LC–MS internal standardization), always rely on the CoA for exact concentration, purity, and solvent recommendations specific to the supplied lot.

Quality and Grades

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

Interpretation and implications (general guidance):

• Isotopically labeled standards such as regorafenib‑d3 are commonly provided at high chemical purity with defined isotopic enrichment and positional labeling; however, exact assay, isotopic purity (%D incorporation), residual solvents, and counterions (if any) must be confirmed on the lot-specific CoA.
• For quantitative LC–MS/MS assays, purity and isotopic enrichment directly impact accuracy (isotopic overlap with analyte) and should be verified. Even trace unlabeled parent (d0) content can bias quantitation in high-sensitivity methods.
• If HPLC or LC–MS grade is claimed, that typically indicates low UV background, low nonvolatile residue, and suitability for trace analysis. Because this entry does not state a grade, users should qualify the material in their own method (system suitability, response factors) and consult the CoA for chromatographic purity and isotopic distribution.
• Stabilizers: Not specified for this item. If a stabilizer were present, it would be disclosed on the CoA; stabilizers can affect UV/LC baselines and mass spectra.

Recommendation: Prior to use as an internal standard, document retention time match with the analyte, confirm isotope spacing (+3.0 Da cluster), and evaluate potential in-source fragmentation or adduct formation under your method conditions.

Reaction and Applications

Primary use case (research): isotopically labeled internal standard for analytical chemistry.

• LC–MS/MS quantitation: Regorafenib‑d3 provides a +3 Da mass shift relative to the analyte, co-elutes with the parent, and compensates for extraction recovery and ionization variability. Typical use includes spiking a fixed concentration into plasma, tissue homogenates, or formulation samples for calibration curves and QC samples.
• Metabolism and stability studies: Employed to distinguish analyte from labeled control in microsomal/S9/hepatocyte incubations and to probe matrix effects or track degradation pathways without ambiguity from in-source fragments.
• Recovery and matrix-effect assessment: Evaluate SPE or protein precipitation protocols by comparing d3/internal standard response across matrices.
• Isotope-dilution workflows: Supports absolute quantification when calibration standards are prepared with matched analyte/IS ratios.

Synthetic/chemical reaction applications: Limited; deuteration is used for mechanistic kinetic isotope effect (KIE) studies, but for this specific labeled drug analog, the primary role is analytical rather than as a reactive substrate.

Practical tips:

• Verify isotopic purity and exact labeled positions (CoA). Label scrambling is not expected under normal conditions but confirm by HRMS if critical.
• Optimize MRM transitions to avoid overlap between d0 fragments and d3 parent; choose fragment ions that retain the labeled positions when possible.
• Match retention by ensuring identical mobile phase and gradient for analyte and IS; confirm absence of isotopologue interferences in high-abundance regimes.

Reaction Conditions

This product is not primarily intended for use as a reagent in chemical transformations; therefore, no item-specific reaction condition guidance is provided. The following notes are oriented to analytical use and literature-based stability considerations.

Analytical preparation (general guidance):

• Stock solutions: Prepare at 1–10 mM in anhydrous DMSO or DMF. Filter through 0.2 µm PTFE if particulate is observed. Store aliquots at −20°C to minimize freeze–thaw cycles.
• Working solutions: Dilute into acetonitrile or acetonitrile/water with 0.1% formic acid for LC–MS/MS; keep organic content sufficient to avoid precipitation (>20% v/v during intermediate dilutions).
• Stability: Protect from light and moisture. Avoid prolonged exposure to strong acids/bases or elevated temperature that could hydrolyze urea/amide linkages (literature, parent behavior).

LC–MS/MS method pointers (general):

• Source: ESI positive mode commonly provides robust ionization for urea-containing kinase inhibitors; assess negative mode as needed for confirmatory ions.
• Transitions: Choose quantifier/qualifier ions that retain the deuterated moiety to preserve the +3 Da separation from d0.
• Chromatography: Reversed-phase C18 with gradient elution (water + 0.1% FA / acetonitrile + 0.1% FA) is typical. Column temperature 30–45°C can improve peak shape for lipophilic analytes.

Item-specific kinetic/thermodynamic data, rate constants, or degradation half-lives: Not specified for this item; consult your method validation and the CoA.

Safety and Handling

Item-specific GHS classifications for this product are not provided below. Always consult the product SDS for authoritative hazard, precautionary, and emergency information.

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

General laboratory precautions (appropriate for small-molecule research chemicals):

• PPE: Wear lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use a certified chemical fume hood to avoid inhalation of dust or aerosols.
• Handling: Avoid breathing dust; minimize skin/eye contact. Use dedicated tools for weighing microgram–milligram quantities, especially for bioactive kinase inhibitor analogs.
• Incompatibilities: Avoid strong oxidizers and strong acids/bases that may promote hydrolysis of urea/amide functionalities (general guidance). Keep away from ignition sources when using organic solvents.
• First aid (general):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with plenty of water for at least 15 minutes; remove contaminated clothing; obtain medical advice if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Environmental: Prevent release to the environment; collect spills with inert absorbent and dispose of according to institutional and regulatory requirements.
• Special risks: Fine powders of lipophilic aromatics can be nuisance dusts; for isotopically labeled bioactive analogs, treat as potentially potent and handle with containment.

Storage: See the Storage & Reconstitution tab; per Product Data, store at −20°C. Shipments are supplied cold (ice chest + ice pads).

Solvent Selection

This compound is a lipophilic, polyaromatic urea derivative; the d3 label does not materially change solubility relative to the parent. Item-specific solubility is not provided; the following guidance is literature/general for regorafenib-like scaffolds.

• Polarity/miscibility class (general): Low aqueous solubility; soluble in polar aprotic organics. Typical stock solutions are prepared in DMSO or DMF.
• Recommended solvents for stocks:
  • DMSO: Common for 1–10 mM analytical standards; miscible with aqueous mobile phases after dilution.
  • DMF: Alternative to DMSO with similar solubilizing power.
  • ACN: May dissolve at lower concentrations; useful for LC–MS sample prep; consider small DMSO co-solvent.
  • Dichloromethane/ethyl acetate: Useful for preparative workup but less common for analytical stocks.
• Aqueous media: Poor solubility; if needed, use minimal DMSO co-solvent (e.g., 0.1–1% v/v) and surfactant-free buffers to avoid ion suppression in LC–MS.

Small comparison (general):

• DMSO vs ACN: DMSO affords higher solubility and long-term stability for concentrated stocks; ACN is preferable for direct LC–MS injection at low % organic without excessive viscosity.

Practical notes:

• Filter organic working solutions (0.2 µm PTFE) before LC–MS.
• Avoid strong bases/acids in solution that may degrade urea/amide motifs.
• Record exact solvent lot and water content for regulated bioanalytical workflows.

Item-specific solubility/UV-cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Storage and Reconstitution

Item-specific conditions from Product Data:

• Storage conditions: Store at −20°C.
• Shipped in: Ice chest + ice pads.

General guidance for reconstitution and handling of isotopically labeled small-molecule standards:

• Upon receipt: Allow the sealed container to equilibrate to room temperature in a desiccator before opening to avoid moisture condensation.
• Reconstitution solvent: Use anhydrous DMSO or DMF to prepare concentrated stocks. If provided as a solution, verify solvent, concentration, and stabilizers on the CoA/label before further dilution.
• Working solutions: Dilute into acetonitrile or acetonitrile/water immediately prior to use. Maintain low final DMSO content (≤1% v/v) in LC–MS injections to ensure consistent chromatography.
• Aliquoting: Prepare single-use aliquots to minimize freeze–thaw cycles and isotopic dilution from moisture ingress.
• Light and moisture protection: Store in amber vials with PTFE-lined caps; use desiccant. Purge headspace with inert gas if prolonged storage is anticipated.
• Stability: Not specified for this item; refer to CoA/Spec Sheet for shelf life, in-solution stability, and recommended retest intervals.

Disposal: Follow institutional procedures for small quantities of organic, halogenated/lipophilic compound waste. Avoid drain disposal.

Structure and Identity

Brief overview: Regorafenib‑d3 is a deuterium-labeled analog of regorafenib intended for research use (e.g., analytical/internal standard applications). Item-specific structure descriptors are largely not specified for this catalog entry; literature descriptions of the parent scaffold are provided for contextual understanding.

• SKU: R646852
• Product name: Regorafenib‑d3
• CAS: 1255386-16-3 (literature identifier for the d3 analog)
• PubChem CID: 49822400 (literature)
• InChIKey: 87171 (as provided; truncated/incomplete — refer to CoA/SDS for the authoritative identifier)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (literature, parent regorafenib):

• Polyfunctional small molecule with a diphenylurea core linking two aryl systems.
• One aryl bears halogen substituents (commonly F/Cl) and a heteroaryl or substituted phenyl ring; the other aryl connects through a urea to a carbonyl-containing side chain.
• Regorafenib‑d3 incorporates three deuterium atoms at defined positions relative to the parent, preserving chemical identity while providing a +3.0 Da mass shift for MS workflows.

2D structure description (literature):

• Central urea (–NH–CO–NH–) flanked by two substituted phenyl rings; one ring further substituted with halogens; the other ring tethered to an amide/oxo functionality. No stereogenic centers in the parent scaffold. Deuterium substitution does not change connectivity, only isotopic composition.

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Synthetic Utility

As a deuterated analog tailored for analytical use, regorafenib‑d3 is not typically employed as a building block in multistep synthesis. Nevertheless, understanding the functional group landscape of the parent scaffold can guide handling or limited derivatization studies.

Functional group context (literature, parent):

• Diphenylurea linkage (–NH–CO–NH–): susceptible to strong-base or strong-acid hydrolysis under forcing conditions; stable under neutral to mildly basic/acidic analytical conditions.
• Amide/carbonyl substituents on an aryl ring: can participate in hydrogen bonding; relatively inert under mild conditions.
• Halo/fluoroaryl motifs: enable cross-coupling at activated positions in synthetic campaigns (not typically altered in the finished labeled standard).

Potential niche uses:

• Isotope tracing: In mechanistic studies, d3 positional labels can help confirm fragmentation pathways in MS/MS or assess minimal KIE in specific C–H(D) sites.
• Conjugation studies: While uncommon, the scaffold could be appended to tags or surfaces for binding assays, using carbamate/urea chemistry, provided labeling positions do not scramble.

Caveats:

• Any transformation risks loss or redistribution of deuterium; maintain anhydrous, non-exchange conditions if labels are on exchangeable positions. Consult the CoA for precise labeling sites before attempting any derivatization.

Target Specificity

Not applicable to this product’s format. Regorafenib‑d3 is a small-molecule isotopically labeled standard, not an antibody, enzyme, or affinity reagent. No clone, isotype, antigen, or species reactivity applies.

Context (literature, parent compound): The unlabeled parent is reported to interact with multiple kinase targets (e.g., VEGFRs, PDGFRs, RAF kinases). This information is provided solely to rationalize its monitoring in analytical assays; it does not imply any biological targeting specification for this item.

For target-binding assays, use validated biological reagents (antibodies, proteins) and employ this product only as a chemical standard when needed.

자주 묻는 질문

What is the purity of this product?

This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1255386-16-3, the molecular formula is C21H12D3ClF4N4O3, and the molecular weight is 485.83 g/mol. InChIKey FNHKPVJBJVTLMP-FIBGUPNXSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.