14663-23-1

Basic information

• Product Name: Dantrolene sodium salt
• Synonyms: 1-[[5-(p-Nitrophenyl)furfurylidene]amino]-hydantoin sodium salt anhydrous;DantroloneSodium;Dantrolene Sodium Salt SODIUM DANTROLENE;DANTRIUM;DANTROLENE NA;DANTROLENE SODIUM SALT;1-[[[5-(4-NITROPHENYL)-2-FURANYL]METHYLENE]AMINO]-2,4-IMIDAZOLINEDIONE SODIUM SALT
• CAS NO: 14663-23-1
• Molecular Formula: C₁₄H₉N₄O₅*Na
• Molecular Weight: 336.23
• EINECS: 238-706-8
• Product Categories: pharmacetical;API's;InsP3/Ryanodine receptor;Cardiovascular APIs
• Mol File: 14663-23-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 85°C 4mm
• Flash Point: 283.1oC
• Appearance: COA
• Storage Temp.: Store at RT
• Solubility: Soluble in DMSO (up to 3 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or DMF/ethanol may be stored at -20°C for up to 1 month.
• Merck: 14,2816
• CAS DataBase Reference: Dantrolene sodium salt(CAS DataBase Reference)
• NIST Chemistry Reference: Dantrolene sodium salt(14663-23-1)
• EPA Substance Registry System: Dantrolene sodium salt(14663-23-1)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 2
• RTECS: MU3875000
• Hazardous Substances Data: 14663-23-1(Hazardous Substances Data)

Usage

Description

Dantrolene is an inhibitor of calcium release from the sarcoplasmic reticulum (IC50 = 0.3 μM). It binds to sarcoplasmic reticulum vesicles isolated from normal and malignant hyperthermia-susceptible (MHS) pigs with Kd values of 0.3 and 0.09 μM, respectively. Dantrolene reduces spontaneous calcium wave frequency and amplitude in the presence of calmodulin in isolated mouse cardiomyocytes with IC50 values of 0.42 and 0.19 μM, respectively. It reduces the magnitude of electrically stimulated twitch tensions in isolated rat extensor digitorum longus and soleus muscles (IC50 = 3 μg/ml) and MHS pigs (ED50 = 0.85 mg/kg). Formulations containing dantrolene have been used in the treatment of malignant hyperthermia.

Chemical Properties

mp 279-280C 3415821

Uses

Different sources of media describe the Uses of 14663-23-1 differently. You can refer to the following data:
1. Skeletal muscle relaxant;Blocker of Ca2+ release
2. Dantrolene Sodium Salt is a skeletal muscle relaxant, which inhibits intracellular Ca 2+release from the sarcoplasmic reticulum.

Definition

ChEBI: The anhydrous sodium salt of dantrolene.

Brand name

Dantrium (Procter & Gamble).

Biological Activity

Inhibits release of Ca 2+ from sarcoplasmic reticulum via inhibition of ryanodine receptor (RYR) channels. Displays selectivity for RYR1 and RYR3 over RYR2. Protective against the effects of a variety of conditions and agents, including excitatory amino acids. Skeletal muscle relaxant and neuroprotectant.

References

1) Zhao?et al.?(2001),?Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity; J. Biol. Chem.,?276?13810 2) Frandsen and Schousboe (1992),?Mobilization of dantrolene-sensitive intracellular calcium pools is involved in the cytotoxicity induced by quisqualate and N-methyl-D-aspartate but not by 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate and kainite in cultured cerebral cortical neurons; Proc. Natl. Acad. Sci. USA,?89?2590 3) Muehlschlegel and Sims (2009),?Dantrolene: mechanisms of neuroprotection and possible clinical applications in the neurointensive care unit; Neuro. Crit. Care,?10?103 4) Lu?et al.?(2014),?A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome; Proc. Natl. Acad. Sci. USA,?111?E5292

InChI:InChI=1/C14H10N4O5.Na/c19-13-8-17(14(20)16-13)15-7-11-5-6-12(23-11)9-1-3-10(4-2-9)18(21)22;/h1-7H,8H2,(H,16,19,20);/b15-7+;

Synthetic route

dantrolene (7261-97-4) → 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 3h;	100%

5-(4-nitrophenyl)-2-furaldehyde (7147-77-5) → 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / H2O; dimethylformamide 2: 100 percent / CH3ONa / methanol / 3 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → dantrolene (7261-97-4)

Conditions	Yield
With acetic acid In N,N-dimethyl-formamide at 20℃;	98%

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) + tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate (89151-46-2) → 3-{[(1-tert-butoxycarbonyl)piperidin-4-yl]ethyl}-1-{[5-(4-nitrophenyl)furfurylidene]amino}imidazolidine-2,4-dione

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	96.4%

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) + tert-butyl 4-(iodomethyl)piperidine-1-carboxylate (145508-94-7) → 3-{[(1-tert-butoxycarbonyl)piperidin-4-yl]methyl}-1-{[5-(4-nitrophenyl)furfurylidene]amino}imidazolidine-2,4-dione

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	51.6%

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) + di-tert-butyl chloromethyl phosphate (229625-50-7) → C23H29N4O9P

Conditions	Yield
With sodium iodide In N,N-dimethyl-formamide at 0 - 20℃; for 64h; Temperature;	45%

N-[(1,1-dimethylethoxy)carbonyl]glycine chloromethyl ester (34573-36-9) + 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C22H23N5O9

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 110h;	27%

tert-butyl chloromethyl butanedioate (432037-43-9) + 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C23H24N4O9

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 20h;	20%

1-benzyl-4-(2-hydroxyethyl)piperazine (3221-20-3) + 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → 3-[(4-benzylpiperizin-1-yl)ethyl]-1-{[5-(4-nitrophenyl)furfurylidene]amino}imidazolidine-2,4-dione

Conditions	Yield
Stage #1: 1-benzyl-4-(2-hydroxyethyl)piperazine With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 0.333333h; Mitsunobu Displacement; Stage #2: 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt In tetrahydrofuran at 60℃;	5.7%

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) + 2-bromoethanol (540-51-2) → (2-(2-hydroxyethoxy)-1-(((5-(4-nitrophenyl)furan-2-yl)methylene)amino)-1,5-dihydro-4H-imidazole-4-one)

Conditions	Yield
Stage #1: 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt With potassium carbonate In tetrahydrofuran; water for 0.5h; Stage #2: 2-bromoethanol In tetrahydrofuran; water at 20℃; for 24h;

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → 3-[(1-benzylpiperidin-4-yl)ethyl]-1-{[5-(4-nitrophenyl)furfurylidene]amino}imidazolidine-2,4-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 3 h / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C20H21N5O5

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 3 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C21H23N5O5

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 3 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → 3-[(1-benzylpiperidin-4-yl)methyl]-1-{[5-(4-nitrophenyl)furfurylidene]amino}imidazolidine-2,4-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / dichloromethane; 1,4-dioxane / 3 h / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C15H12N4O6

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C15H11ClN4O5

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: phosphorus trichloride / N,N-dimethyl-formamide; acetone / 2.16 h / 0 - 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C21H21N5O8

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 60 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C21H21N5O8*ClH

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 60 °C 4: hydrogenchloride / water; 1,4-dioxane / 2 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C29H33N5O8Si

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C23H19N5O8

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: toluene-4-sulfonic acid / 1,4-dioxane; methanol / 16 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C27H23N5O11

Conditions	Yield
Multi-step reaction with 5 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: toluene-4-sulfonic acid / 1,4-dioxane; methanol / 16 h / 20 °C 5: toluene-4-sulfonic acid / 1,4-dioxane; m-xylene / 16 h / Molecular sieve; Reflux View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C27H23N5O11*C4H11NO3

Conditions	Yield
Multi-step reaction with 6 steps 1: acetic acid / N,N-dimethyl-formamide / 20 °C 2: potassium carbonate / water / 24 h / 20 °C 3: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 4: toluene-4-sulfonic acid / 1,4-dioxane; methanol / 16 h / 20 °C 5: toluene-4-sulfonic acid / 1,4-dioxane; m-xylene / 16 h / Molecular sieve; Reflux 6: water / 3 h / 20 °C View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → C15H11N4O9P(2-)*2Na(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium iodide / N,N-dimethyl-formamide / 64 h / 0 - 20 °C 2.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 2.2: 20 °C / pH 8.5 View Scheme

1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidine-dione sodium salt (14663-23-1) → dantrolene sodium trihemihydrate

Conditions	Yield
With water In methanol at 20 - 30℃; for 6h;

Upstream product

• 7147-77-5 5-(4-nitrophenyl)-2-furaldehyde 
• 7261-97-4 dantrolene 

Downstream Products

• 7261-97-4 dantrolene 

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SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF DANTROLENE AND SODIUM DANTROLENE

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