ChemicalBook >> CAS DataBase List >>NEDOCROMIL SODIUM

NEDOCROMIL SODIUM

CAS No.
69049-74-7
Chemical Name:
NEDOCROMIL SODIUM
Synonyms
Tayled;Tilade;Alocril;Tilarin;Unii-et8if4ks1t;Nedocromil sodium;NEDOCROMIL DISODIUM SALT;NEDOCROMIL SODIUM###Nedocromil;Sodium 9-ethyl-4,6-dioxo-10-propyl-6,9-dihydro-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate;4H-Pyrano[3,2-g]quinoline-2,8-dicarboxylicacid, 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-, sodium salt
CBNumber:
CB81011490
Molecular Formula:
C19H18NNaO7
Molecular Weight:
395.34
MDL Number:
MFCD00941388
MOL File:
69049-74-7.mol
MSDS File:
SDS
Last updated:2023-06-08 09:02:09

NEDOCROMIL SODIUM Properties

storage temp. Inert atmosphere,2-8°C
solubility H2O: soluble20mg/mL, clear
form powder
color , white to beige to brown
FDA UNII ET8IF4KS1T

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H319
Precautionary statements  P264-P280-P305+P351+P338-P337+P313P
WGK Germany  3
NFPA 704
0
2 0

NEDOCROMIL SODIUM price More Price(24)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich SML1101 Nedocromil sodium ≥98% (HPLC) 69049-74-7 10mg $92.2 2024-03-01 Buy
Sigma-Aldrich SML1101 Nedocromil sodium ≥98% (HPLC) 69049-74-7 50mg $357 2024-03-01 Buy
Cayman Chemical 24005 Nedocromil (sodium salt) ≥98% 69049-74-7 5mg $44 2024-03-01 Buy
Cayman Chemical 24005 Nedocromil (sodium salt) ≥98% 69049-74-7 10mg $84 2024-03-01 Buy
Cayman Chemical 24005 Nedocromil (sodium salt) ≥98% 69049-74-7 25mg $193 2024-03-01 Buy
Product number Packaging Price Buy
SML1101 10mg $92.2 Buy
SML1101 50mg $357 Buy
24005 5mg $44 Buy
24005 10mg $84 Buy
24005 25mg $193 Buy

NEDOCROMIL SODIUM Chemical Properties,Uses,Production

Description

Nedocromil sodium is an antiallergic agent with broader mast cell stabilizing properties than related cromolyn sodium. Administered as an aerosol, it is useful in the treatment of bronchial asthma and related diseases.

Description

Nedocromil is a mast cell stabilizer. It inhibits IgE-induced histamine release from rat peritoneal mast cells cocultured with 3T3 cells (MC/3T3) and preincubated with IL-2 when used at a concentration of 10 μM in acute (1 hour) and chronic (5 days) assays. Nedocromil prevents early- and late-phase bronchoconstriction in a guinea pig model of asthma induced by ovalbumin. It also prevents conjunctival edema and erythema and reduces mast cell degranulation in a rat model of conjunctivitis when administered intravenously at a dose of 2 mg/kg. Formulations containing nedocromil have been used in the treatment of allergic conjunctivitis and asthma.

Originator

Fisons (United Kingdom)

Uses

Anti-allergic (prophylactic.

Uses

Nedocromil Sodium (Technical Grade) is a medication considered as mast cell stabilizer which act to prevent wheezing, shortness of breath, and other breathing problems caused by asthma.

Indications

nedocromil sodium(Tilade) is chemically related drugs called chromones that is used for the prophylaxis of mild or moderate asthma. It is administered by inhalation and has very good safety profiles, making them particularly useful in treating children.

Definition

ChEBI: Nedocromil sodium is an organic sodium salt. It contains a nedocromil(2-).

Manufacturing Process

4,6-Dioxo-10-propyl-4H,6H-pyrano[3,2-]quinoline-2,8-dicarbxylic acid disodium salt was prepared in 8 steps
1. 4-Acetamido-2-allylacetophenone
4-Acetamido-2-hydroxyacetophenone (19.3 g), allyl bromide (12.1 ml) and hydrous potassium carbonate (21.5 g) were stirred in dry dimethylformamide (250 ml) at room temperature for 24 hours. The reaction mixture was poured into water and the product was extracted with ethyl acetate. The organic solution was then washed well with water dried over magnesium sulphate and evaporated to dryness. The sub-title product was obtained as buff coloured solid (20.5 g). The structure of the product was confirmed by NMR and mass spectroscopy.
2. 4-Acetamido-3-allyl-2-hydroxyacetophenone
The above allyl ether (18.4 g) was heated at 200-210°C for 4 hours. 17.1 g of the thermally rearranged sub- title product was obtained as a brown solid. Again the structure was confirmed by NMR and mass spectroscopy.
3. 4-Acetamido-2-hydroxy-3-propyl acetophenone
The product of step 2 (17 g) was dissolved in glacial acetic acid and hydrogenated in the presence of Adams catalyst until hydrogen uptake had ceased. The catalyst was filtered off through a keiselguhr filter and the filtrate was evaporated to leave 13.0 g of almost colorless solid. The mass and NMR spectra confirmed the structure of product.
4. Ethyl-7-acetamido-4-oxo-8-propyl-4H-l-benzopyran-2-carboxylate
A mixture of diethyl oxalate (19.3 g; 17.9 ml) and the above product of step 3 (12.4 g) in dry ethanol (100 ml) was added to a stirred solution of sodium ethoxide in ethanol (prepared by dissolving sodium (6.1 g) in dry ethanol (200 ml)). The reaction mixture was refluxed for 3 hours and then poured into dilute hydrochloric acid and chloroform. The chloroform layer was separated, washed with water and dried. The solvent was evaporated to leave a brown solid which was dissolved in ethanol (300 ml) containing concentrated hydrochloric acid (3 ml) and the whole was refluxed for 1 hour. The reaction mixture was poured into water and the product was extracted into ethyl acetate which was washed with water and dried. The solvent was evaporated to leave 10 g of a sticky solid which had mass and NMR spectra consistent with the expected product.
5. Ethyl 7-amino-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate
A solution of the amide of step 4 (10 g) in ethanol (300 ml), containing concentrated hydrochloric acid (5 ml), was refluxed for 8 hours. The reaction mixture was diluted with water and extracted into ethyl acetate. The extract was washed with water, dried and the solvent was evaporated to leave a dark brown semi-solid. This was chromatographed on a silica gel column, using ether as eluant to give 4.8 g of the required product whose structure was confirmed by mass and NMR spectral evidence; mp 84-87°C.
6.8-Ethoxycarbonyl-2-methoxycarbonyl-4,6-dioxo-10-propyl-4H,6Hpyrano[3.2-g]quinoline
The amino benzopyran of step 5 (2.0 g) and dimethyl acetylene dicarboxylate (1.24 g; 1.01 ml) were refluxed in ethanol (30 ml) for 26 hours. The reaction mixture was cooled to 0°C and the insoluble yellow-brown solid was collected by filtration and washed with a little ethanol and dried to give 2.0 g of a product which was a mixture of maleic and fumaric esters obtained by Michael addition of the amine to the acetylene. This mixture of esters (2.0 g) was treated with polyphosphoric acid (30 ml) and heated on the steam bath with stirring for 20 minutes. The reaction mixture was then poured onto ice and stirred with ethyl acetate. The organic layer was separated, washed with water and dried. The solvent was evaporated to leave 1.6 g of a yellow orange solid. Recrystallisation of this solid from ethyl acetate gave the required product as fluffy orange needles, mp 187°-188°C.
7. 4,6-Dioxo-10-propyl-4H,6H-pyrano[3.2-g]quinoline-2,8-dicarboxylic acid
The above bis ester (2.5 g) was refluxed with sodium bicarbonate (1.64 g) in ethanol (100 ml) and water (50 ml) for 1.5 hours. The whole was poured into water and acidified to precipitate a gelatinous solid. This was collected by filtration, refluxed with ethanol and the product was separated by centrifugation (1.4 g), mp 303°-304°C dec. The structure of the product was confirmed by mass and NMR evidence.
8. Disodium 4,6-dioxo-10-propyl-4H,6H-pyrano[3,2-g]quinoline-2,8- dicarboxylate
The bis acid from step 6 (1.35 g) and sodium bicarbonate (0.661 g) in water (150 ml) were warmed and stirred until a clear solution was obtained. This solution was filtered and the filtrate was freeze dried to give 1.43 g of the required disodium salt.

brand name

Alocril (Allergan); Tilade (King); Tilade (Sanofi Aventis).

Therapeutic Function

Antiallergic, Anti-asthmatic

General Description

Nedocromil sodium, disodium9-ethyl-6, 9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3, 2-g]quinoline-2,8-dicarboxylate (Tilade), is structurally relatedto cromolyn and displays similar, but broader, pharmacologicalactions. It was available as an aerosol in ametered-dose inhaler for asthma treatment, and currently remainsavailable as ophthalmic solution for the treatmentof itching associated with allergic conjunctivitis. The inhalationformulation was marketed for maintenance therapyin the management of patients with mild-to-moderatebronchial asthma, but since has been withdrawn.

Pharmacokinetics

Nedocromil sodium was developed by changing the furan ring of khellin to a piperidinone ring. In vitro, nedocromil sodium inhibits the release of inflammatory response mediators from a variety of cells, including neutrophils, mast cells, macrophages, and platelets. Inhaled nedocromil sodium is poorly absorbed into the systemic circulation, with approximately 3% of an inhaled dose excreted in the urine during the first 6 hours after administration. Only 2% of orally dosed nedocromil sodium is bioavailable, 89% of which is protein bound. When administered IV, nedocromil sodium is not metabolized and is excreted unchanged in the bile and the urine. Nedocromil sodium is available in aerosol canisters for oral inhalation via a mouthpiece.

Clinical Use

nedocromil sodium is used almost exclusively for the prophylactic treatment of mild to moderate asthma and should not be used for the control of acute bronchospasm. This agent is effective in about 60 to 70% of children and adolescents with asthma. Unfortunately, there is no reliable means to predict which patients will respond.It is less effective in older patients and in patients with severe asthma. It may take up to 4 to 6 weeks of treatment for cromolyn sodium to be effective in chronic asthma, but it is effective after a single dose in exercise-induced asthma. With respect to clinical efficacy, cromolyn sodium and nedocromil sodium do not differ in a substantial way.

Side effects

nedocromil sodium is the least toxic of available therapies for asthma. Adverse reactions are rare and generally minor. Those occurring in fewer than 1 in 10,000 patients include transient bronchospasm, cough or wheezing, dryness of throat, laryngeal edema, swollen parotid gland, angioedema, joint swelling and pain, dizziness, dysuria, nausea, headache, nasal congestion, rash, and urticaria.

NEDOCROMIL SODIUM Preparation Products And Raw materials

Global( 46)Suppliers
Supplier Tel Email Country ProdList Advantage
BOC Sciences
+1-631-485-4226 inquiry@bocsci.com United States 19553 58
CONIER CHEM AND PHARMA LIMITED
+8618523575427 sales@conier.com China 47465 58
Hebei Bonster Technology Co.,Limited
+8613315996897 bsterltd.wendy@gmail.com China 796 58
TargetMol Chemicals Inc.
+1-781-999-5354 +1-00000000000 marketing@targetmol.com United States 19892 58
AFINE CHEMICALS LIMITED
0571-85134551 info@afinechem.com CHINA 15377 58
Dayang Chem (Hangzhou) Co.,Ltd.
571-88938639 +8617705817739 info@dycnchem.com CHINA 52867 58
LEAP CHEM CO., LTD.
+86-852-30606658 market18@leapchem.com China 24738 58
GIHI CHEMICALS CO.,LIMITED
+8618058761490 info@gihichemicals.com China 50001 58
Shanghai Acmec Biochemical Technology Co., Ltd.
+undefined18621343501 product@acmec-e.com China 33349 58
Amadis Chemical Company Limited
571-89925085 sales@amadischem.com China 132020 58
NEDOCROMIL DISODIUM SALT [9-Ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3,2-g]quinoline]-2,8-dicarboxylic acid disodium salt Nedocromil sodium 4H-Pyrano(3,2-G)quinoline-2,8-dicarboxylic acid, 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-, disodium salt Alocril Tilade Unii-et8if4ks1t Tayled Tilarin 4H-Pyrano[3,2-g]quinoline-2,8-dicarboxylicacid, 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-, sodium salt 4H-Pyrano[3,2-g]quinoline-2,8-dicarboxylicacid, 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-, sodium salt (1:2) NEDOCROMIL SODIUM###Nedocromil Sodium 9-ethyl-4,6-dioxo-10-propyl-6,9-dihydro-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate 69049-74-7 C19H15NNa2O7 C19H15NO72Na API