1. Product Overview
Capadenoson (CAS 544417-40-5), also known as BAY 68-4986, is a potent, selective, and orally bioactive partial agonist of the adenosine A1 receptor (A1AR). With the molecular formula C₂₅H₁₈ClN₅O₂S₂ and a molecular weight of 520.03 g/mol, this complex heterocyclic compound features a 2-aminopyridine-3,5-dicarbonitrile core linked via a methylthio bridge to a 2-(4-chlorophenyl)thiazole, with a 4-(2-hydroxyethoxy)phenyl substituent. Capadenoson exhibits GTPγS binding EC₅₀ = 0.1 nM (74% efficacy vs. full agonist CCPA) and demonstrates biased agonism toward cAMP signal transduction (pEC₅₀ = 8.94 for cAMP vs. 6.20 for Ca²⁺/pERK), while maintaining minimal A2A and A3 receptor activity. It provides cardioprotection in ischemia-reperfusion injury models (25–28% infarct size reduction at 0.1–0.3 mg/kg i.v.) without the risk of atrioventricular (AV) block associated with full A1 agonists.
2. Key Features and Benefits
• Ultra-High A1R Potency & Selectivity: Binds A1R with EC₅₀ = 0.1 nM (GTPγS) with >1000-fold selectivity over A2A and A3 receptors, ensuring clean mechanistic studies of A1R-specific pathways.
• Biased Agonism Profile: Preferentially couples to cAMP inhibition (Gαᵢ pathway) over Ca²⁺ mobilization and ERK phosphorylation, making it a valuable tool for dissecting A1R signal transduction bias.
• Cardioprotection Without AV Block: At concentrations up to 10 μM, maintains 100% heart rate in isolated perfused rat hearts (whereas full agonist CCPA reduces rate to 90%), enabling safe cardiovascular research.
• Orally Bioavailable: Suitable for in vivo administration via oral gavage or i.v. injection, with demonstrated efficacy in rat ischemia-reperfusion models.
• Well-Characterized: >50 peer-reviewed publications validate its pharmacology, PK/PD profile, and cardioprotective efficacy across multiple species and model systems.
3. Major Applications
• Cardiovascular Research: Used to study A1R-mediated cardioprotection in myocardial ischemia-reperfusion injury, preconditioning, and postconditioning protocols in rat, mouse, and porcine models.
• Adenosine Receptor Pharmacology: Employed to dissect A1R vs. A2A/A2B/A3 signaling bias, G-protein coupling preferences, and receptor internalization mechanisms.
• Kidney & Renal Research: Investigated for A1R-mediated effects on renal blood flow, glomerular filtration, and sodium handling in physiological and pathological states.
• CNS & Neuroprotection Studies: Applied in models of cerebral ischemia, neuroinflammation, and neurodegenerative diseases where A1R activation confers neuroprotection.
• Drug Discovery & Lead Optimization: Serves as a lead compound for designing next-generation A1R-selective agonists with improved therapeutic windows for heart failure, arrhythmias, and neuroprotection.
• In Vivo PK/PD Studies: Administered in rats and dogs to evaluate pharmacokinetics, receptor occupancy, and dose-response relationships for cardiovascular endpoints.
4. Technical Specifications
Item Description
Product Name Capadenoson (BAY 68-4986)
Synonyms BAY 68-4986; 2-Amino-6-[[[2-(4-chlorophenyl)-4-thiazolyl]methyl]thio]-4-[4-(2-hydroxyethoxy)phenyl]-3,5-pyridinedicarbonitrile; CS-1666
CAS Number 544417-40-5
Molecular Formula C₂₅H₁₈ClN₅O₂S₂
Molecular Weight 520.03 g/mol
MDL Number MFCD09954113
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance Light yellow to yellow crystalline solid or powder
Boiling Point ~787.9 °C (Predicted)
Density ~1.51 g/cm³ (Predicted)
Refractive Index ~1.735 (Predicted)
pKa (Predicted) ~13.98 ± 0.10 (Pyridine N protonation)
Calculated LogP ~6.1
Polar Surface Area (PSA) ~182.4 Ų
Hydrogen Bond Donors 2 (NH₂ + OH)
Hydrogen Bond Acceptors 9
Rotatable Bonds 9
Solubility Soluble: DMSO (≥2 mg/mL, clear solution), DMF, Methanol (slightly), Ethanol (slightly).
Practically Insoluble:Water (high LogP); the hydroxyethoxy side chain provides limited aqueous solubility.
Note:Sonication recommended for DMSO stock preparation.
Spectral Data ¹H NMR (DMSO‑d₆, 400 MHz): δ 3.55 (t, J≈5.0 Hz, 2H, OCH₂CH₂), 3.85 (t, J≈5.0 Hz, 2H, OCH₂), 4.55 (s, 2H, SCH₂), 6.80–7.55 (m, 8H, aromatic H), 7.85 (br s, 1H, Ar-OH), 8.20 (br s, 2H, NH₂).
¹³C NMR (DMSO‑d₆):δ 35.0 (SCH₂), 60.5 (OCH₂), 69.0 (OCH₂), 110–165 (aromatic + heteroaromatic Cs + C≡N), 165.0 (C=N).
SMILES N#CC1=C(C#N)C(=C(N)N=C1SCC2=CSC(=N2)C3=CC=C(Cl)C=C3)OC4=CC=C(OCCO)C=C4
InChI Key CITWCLNVRIKQAF-UHFFFAOYSA-N
Storage (Powder) -20°C (preferred) or 2–8°C, sealed, protected from light & moisture; stable ≥18–24 months
Solution Stability DMSO stocks stable at -20°C for 1–3 months; avoid repeated freeze-thaw; working dilutions should be used within 24 h
HS Code 2934.99.90 / 3822.90.00 (Research Tool)
5. Storage and Handling
• Powder Storage: Store sealed vial at -20°C (or 2–8°C for short-term), protected from light in a desiccated environment. Stable for at least 18–24 months from date of manufacture.
• Stock Solution: Dissolve in anhydrous DMSO to 2–10 mM (1–5 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. Protect from light.
• Working Dilution: Dilute into assay buffer or cell culture medium immediately before use. Final DMSO concentration in assays should not exceed 0.1% (v/v). For in vivo studies, prepare fresh suspension in vehicle (e.g., 5% DMSO + 95% saline with 0.5% CMC, or 10% cyclodextrin solution).
• Freeze-Thaw: Aliquot DMSO stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H361: Suspected of damaging fertility or the unborn child (Reproductive toxicity, Category 2).
• H370: Causes damage to organs (Specific target organ toxicity, Category 1).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P202: Do not handle until all safety precautions have been read and understood.
• P260: Do not breathe dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.
• P308+P311: IF exposed: Call a POISON CENTER or physician.
• P321: Specific treatment (see label).
• P330: Rinse mouth if swallowed.
• P405: Store locked up.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air immediately. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water for at least 15 minutes. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention immediately.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Call a POISON CENTER immediately.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce highly toxic fumes including HCl (hydrogen chloride), HCN (hydrogen cyanide from nitriles), Cl₂ (chlorine gas), SOₓ, CO, and NOₓ. Hydrogen chloride, hydrogen cyanide, and chlorine are extremely toxic and corrosive.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do NOT use combustible materials for cleanup. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood ONLY. Keep container closed when not in use. Store at -20°C (or 2–8°C short-term), protected from light and moisture. Keep away from strong oxidizers, strong acids/bases, and heat sources.
• Hazardous Decomposition Products: Hydrogen chloride (HCl), hydrogen cyanide (HCN), chlorine gas (Cl₂), sulfur oxides (SOₓ), nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially bioactive and reproductively toxic compound.
