Nedocromil CAS 69049-73-6
Introduction：Basic information about Nedocromil CAS 69049-73-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Nedocromil Basic information
| Product Name: | Nedocromil |
| Synonyms: | NEDOCROMIL;FPL-59002;FPL-59002KP;Rapitil;Tilarin：Tilade;4H-Pyrano(3,2-G)quinoline-2,8-dicarboxylic acid, 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-;9-Ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano(3,2-G)chinolin-2,8-dicarbonsaeure;Nedocromilo |
| CAS: | 69049-73-6 |
| MF: | C19H17NO7 |
| MW: | 371.34 |
| EINECS: | |
| Product Categories: | |
| Mol File: | 69049-73-6.mol |
Nedocromil Chemical Properties
| Melting point | 298-300° (dec) |
| Boiling point | 645.5±55.0 °C(Predicted) |
| density | 1.472±0.06 g/cm3(Predicted) |
| storage temp. | Sealed in dry,2-8°C |
| solubility | DMSO: soluble2mg/mL, clear (warmed) |
| pka | 2.19±0.40(Predicted) |
| form | Solid |
| color | white to beige |
Safety Information
| Hazard Codes | Xi |
| Risk Statements | 36 |
| Safety Statements | 26 |
| Description | Nedocromil sodium acts mainly by inhibitingthe release of inflammatory mediators. It has astabilizing action on mast cells similar to thatof DSCG. Nedocromil is capable of inhibitingchloride ion flux in mast cells, epithelial cells,and neurons. This feature may explain why it canprevent responses such as mast cell degranulationand neuronal activation . Nedocromil isgiven by inhalation in the prophylactic controlof asthma and rhinitis . |
| Chemical Properties | Yellow crystalline powder. Melting point 298-300°C (decomposition). Nedocromil disodium salt (Nedocromil sodium, Nedocromil Disodium): C19H15NO7Na2.[69049-74-7]. Light yellow crystalline powder. |
| Originator | Alocril,Allergan,USA |
| Uses | Antiallergic (prophylactic). |
| Definition | ChEBI: Nedocromil is a dicarboxylic acid and an organic heterotricyclic compound. It has a role as a non-steroidal anti-inflammatory drug, an anti-asthmatic drug and an anti-allergic agent. It is a conjugate acid of a nedocromil(2-). |
| Manufacturing Process | 4,6-Dioxo-10-propyl-4H,6H-pyrano[3,2-]quinoline-2,8-dicarbxylic aciddisodium salt was prepared in 8 steps 1. 4-Acetamido-2-allylacetophenone 4-Acetamido-2-hydroxyacetophenone (19.3 g), allyl bromide (12.1 ml) andhydrous potassium carbonate (21.5 g) were stirred in dry dimethylformamide(250 ml) at room temperature for 24 hours. The reaction mixture was pouredinto water and the product was extracted with ethyl acetate. The organicsolution was then washed well with water dried over magnesium sulphate andevaporated to dryness. The sub-title product was obtained as buff colouredsolid (20.5 g). The structure of the product was confirmed by NMR and massspectroscopy. 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 ofthe 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 andhydrogenated in the presence of Adams catalyst until hydrogen uptake hadceased. The catalyst was filtered off through a keiselguhr filter and the filtratewas evaporated to leave 13.0 g of almost colorless solid. The mass and NMRspectra 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 step3 (12.4 g) in dry ethanol (100 ml) was added to a stirred solution of sodiumethoxide 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 intodilute hydrochloric acid and chloroform. The chloroform layer was separated,washed with water and dried. The solvent was evaporated to leave a brownsolid which was dissolved in ethanol (300 ml) containing concentratedhydrochloric acid (3 ml) and the whole was refluxed for 1 hour. The reactionmixture was poured into water and the product was extracted into ethylacetate which was washed with water and dried. The solvent was evaporatedto leave 10 g of a sticky solid which had mass and NMR spectra consistentwith 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), containingconcentrated hydrochloric acid (5 ml), was refluxed for 8 hours. The reactionmixture was diluted with water and extracted into ethyl acetate. The extractwas washed with water, dried and the solvent was evaporated to leave a darkbrown semi-solid. This was chromatographed on a silica gel column, usingether as eluant to give 4.8 g of the required product whose structure wasconfirmed 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 reactionmixture was cooled to 0°C and the insoluble yellow-brown solid was collectedby filtration and washed with a little ethanol and dried to give 2.0 g of aproduct which was a mixture of maleic and fumaric esters obtained by Michaeladdition of the amine to the acetylene. This mixture of esters (2.0 g) wastreated with polyphosphoric acid (30 ml) and heated on the steam bath withstirring for 20 minutes. The reaction mixture was then poured onto ice andstirred with ethyl acetate. The organic layer was separated, washed withwater and dried. The solvent was evaporated to leave 1.6 g of a yellow orangesolid. Recrystallisation of this solid from ethyl acetate gave the requiredproduct 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) inethanol (100 ml) and water (50 ml) for 1.5 hours. The whole was poured intowater and acidified to precipitate a gelatinous solid. This was collected byfiltration, refluxed with ethanol and the product was separated bycentrifugation (1.4 g), mp 303°-304°C dec. The structure of the product wasconfirmed 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. Thissolution was filtered and the filtrate was freeze dried to give 1.43 g of therequired disodium salt. |
| Therapeutic Function | Antiallergic, Anti-asthmatic |
| Clinical Use | Nedocromil is a chromone analogue also used by inhalation as an aerosol, primarily in theprophylaxis of asthma and reversible obstructive airway disease. It inhibits release of allergicmediators, and it is effective in a broad range of patients. An ophthalmic solution is availablefor the treatment of seasonal and perennial allergic conjunctivitis. Other structurally relatedcompounds are not currently available in the United States but are available in other markets. |
Nedocromil Preparation Products And Raw materials
| Raw materials | Sodium bicarbonate-->Diethyl oxalate-->Polyphosphoric acid-->3-Aminophenol-->Allyl bromide-->Dimethyl acetylenedicarboxylate-->Allyl ether-->6-Hydroxy-2(1H)-3,4-dihydroquinolinone-->N1-(4-ACETYL-3-HYDROXYPHENYL)ACETAMIDE-->Sodium ethoxide |
