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Identification
NameNedocromil
Accession NumberDB00716  (APRD01137)
TypeSmall Molecule
GroupsApproved
Description

A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. [PubChem]

Structure
Thumb
Synonyms
9-Ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano(3,2-g)chinolin-2,8-dicarbonsaeure
9-Ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano(3,2-g)quinoline-2,8-dicarboxylic acid
Nedocromil
Nedocromilo
Nedocromilum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alocrilsolution/ drops20 mg/mLophthalmicAllergan, Inc.2000-02-03Not applicableUs
Alocrilliquid2 %ophthalmicAllergan Inc2000-02-29Not applicableCanada
Mirezeliquid2 %ophthalmicAllergan Inc1997-08-062000-03-14Canada
Tilademetered-dose aerosol2 mgoralAventis Pharma Inc1998-12-062006-07-28Canada
Tilade Inhaler 2mg/aemmetered-dose aerosol2 mginhalationFisons Corporation Ltd.1990-12-311999-08-13Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nedocromil Sodiumsolution/ drops20 mg/mLophthalmicAkorn, Inc.2012-09-10Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Nedocromil sodium
ThumbNot applicableDBSALT001179
Categories
UNII0B535E0BN0
CAS number69049-73-6
WeightAverage: 371.3408
Monoisotopic: 371.100501903
Chemical FormulaC19H17NO7
InChI KeyInChIKey=RQTOOFIXOKYGAN-UHFFFAOYSA-N
InChI
InChI=1S/C19H17NO7/c1-3-5-9-16-10(13(21)7-12(18(23)24)20(16)4-2)6-11-14(22)8-15(19(25)26)27-17(9)11/h6-8H,3-5H2,1-2H3,(H,23,24)(H,25,26)
IUPAC Name
9-ethyl-4,6-dioxo-10-propyl-4H,6H,9H-chromeno[7,6-b]pyridine-2,8-dicarboxylic acid
SMILES
CCCC1=C2N(CC)C(=CC(=O)C2=CC2=C1OC(=CC2=O)C(O)=O)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as chromenopyridines. These are aromatic heterocyclic compounds structurally characterized by a pyridine ring fused to a chromene moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrans
Sub Class1-benzopyrans
Direct ParentChromenopyridines
Alternative Parents
Substituents
  • Chromenopyridine
  • Quinoline-2-carboxylic acid
  • Dihydroquinolone
  • Chromone
  • Quinoline
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Pyranone
  • Benzenoid
  • Pyridine
  • Pyran
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Vinylogous amide
  • Oxacycle
  • Azacycle
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of mild to moderate asthma
PharmacodynamicsNedocromil is a anti-inflammatory agent and can be administered directly to the bronchial mucosa. It has significant inhibitory effect on allergen-induced early and late asthmatic reactions and on bronchial hyperresponsiveness.
Mechanism of actionNedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not posess any bronchodilator, antihistamine, or corticosteroid activity.
Related Articles
AbsorptionLow
Volume of distributionNot Available
Protein bindingapproximately 89% protein bound in human plasma over a concentration range of 0.5 to 50 µg/mL
Metabolism

Nedocromil is not metabolized after IV administration and is excreted unchanged.

Route of eliminationIt is not metabolized and is eliminated primarily unchanged in urine (70%) and feces (30%).
Half life~3.3 hours
ClearanceNot Available
ToxicitySide effects include headache, nasal congestion, ocular burning, irritation and stinging, unpleasant taste, cough, difficulty breathing, noisy breathing, shortness of breath, tightness in chest, wheezing, conjunctivitis, blurred vision, change in color vision, difficulty seeing at night, increased sensitivity of eyes to sunlight.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.917
Blood Brain Barrier-0.7048
Caco-2 permeable-0.5125
P-glycoprotein substrateSubstrate0.5954
P-glycoprotein inhibitor INon-inhibitor0.8426
P-glycoprotein inhibitor IINon-inhibitor0.5435
Renal organic cation transporterNon-inhibitor0.8157
CYP450 2C9 substrateNon-substrate0.8194
CYP450 2D6 substrateNon-substrate0.8091
CYP450 3A4 substrateNon-substrate0.5338
CYP450 1A2 substrateInhibitor0.7062
CYP450 2C9 inhibitorNon-inhibitor0.8555
CYP450 2D6 inhibitorNon-inhibitor0.9076
CYP450 2C19 inhibitorNon-inhibitor0.6715
CYP450 3A4 inhibitorNon-inhibitor0.8646
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8278
Ames testNon AMES toxic0.6198
CarcinogenicityNon-carcinogens0.9488
BiodegradationNot ready biodegradable0.9798
Rat acute toxicity2.6400 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9113
hERG inhibition (predictor II)Non-inhibitor0.8385
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Allergan inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
Liquidophthalmic2 %
Solution/ dropsophthalmic20 mg/mL
Metered-dose aerosoloral2 mg
Metered-dose aerosolinhalation2 mg
Prices
Unit descriptionCostUnit
Alocril 2% Solution 5ml Bottle100.57USD bottle
Alocril 2% eye drops19.34USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE38628 No1992-08-222012-08-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point299 dec °CPhysProp
water solubility145 mg/LNot Available
logP2.22SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0459 mg/mLALOGPS
logP2.18ALOGPS
logP2.5ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)2.28ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area121.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity98.09 m3·mol-1ChemAxon
Polarizability36.95 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Andrew R. Clark, “Nedocromil sodium compositions and methods for their preparation.” U.S. Patent US4935244, issued July, 1988.

US4935244
General ReferencesNot Available
External Links
ATC CodesR01AC07R03BC03S01GX04
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (362 KB)
MSDSNot Available
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
suppressor
General Function:
Leukotriene receptor activity
Specific Function:
Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affini...
Gene Name:
CYSLTR1
Uniprot ID:
Q9Y271
Molecular Weight:
38540.55 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Monteseirin J, Chacon P, Vega A, Sanchez-Monteseirin H, Asturias JA, Martinez A, Guardia P, Perez-Cano R, Conde J: L-selectin expression on neutrophils from allergic patients. Clin Exp Allergy. 2005 Sep;35(9):1204-13. [PubMed:16164449 ]
  4. Yazid S, Leoni G, Getting SJ, Cooper D, Solito E, Perretti M, Flower RJ: Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1718-24. doi: 10.1161/ATVBAHA.110.209536. Epub 2010 Jun 17. [PubMed:20558817 ]
  5. Radeau T, Godard P, Chavis C, Michel FB, Descomps B, Damon M: Effect of nedocromil sodium on sulfidopeptide leukotrienes-stimulated human alveolar macrophages in asthma. Pulm Pharmacol. 1993 Mar;6(1):27-31. [PubMed:8386571 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Leukotriene receptor activity
Specific Function:
Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = ...
Gene Name:
CYSLTR2
Uniprot ID:
Q9NS75
Molecular Weight:
39634.815 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Monteseirin J, Chacon P, Vega A, Sanchez-Monteseirin H, Asturias JA, Martinez A, Guardia P, Perez-Cano R, Conde J: L-selectin expression on neutrophils from allergic patients. Clin Exp Allergy. 2005 Sep;35(9):1204-13. [PubMed:16164449 ]
  4. Yazid S, Leoni G, Getting SJ, Cooper D, Solito E, Perretti M, Flower RJ: Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1718-24. doi: 10.1161/ATVBAHA.110.209536. Epub 2010 Jun 17. [PubMed:20558817 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Receptor activity
Specific Function:
High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:2161213, PubMed:2176894, PubMed:10514456, PubMed:15153520). Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release (PubMed:2161213, PubMed:1712023, PubMed:15153520). This response is mediated via a G-protein that activates a...
Gene Name:
FPR1
Uniprot ID:
P21462
Molecular Weight:
38445.115 Da
References
  1. Peroni DG, Melotti P, Piacentini GL, Bonizzato C, Boner AL: Effects of nedocromil sodium on the binding of N-formyl-methionyl-leucyl-phenylalanine in human neutrophils. Agents Actions. 1992 Jul;36(3-4):212-4. [PubMed:1326878 ]
  2. Carolan EJ, Casale TB: Effects of nedocromil sodium and WEB 2086 on chemoattractant-stimulated neutrophil migration through cellular and noncellular barriers. Ann Allergy. 1992 Oct;69(4):323-8. [PubMed:1329582 ]
  3. Warringa RA, Mengelers HJ, Maikoe T, Bruijnzeel PL, Koenderman L: Inhibition of cytokine-primed eosinophil chemotaxis by nedocromil sodium. J Allergy Clin Immunol. 1993 Mar;91(3):802-9. [PubMed:8384226 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
unknown
General Function:
Prostaglandin j receptor activity
Specific Function:
Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate (By similarity).
Gene Name:
PTGDR
Uniprot ID:
Q13258
Molecular Weight:
40270.11 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lane SJ, Lee TH: Mast cell effector mechanisms. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2. [PubMed:8939179 ]
  4. Ahluwalia P, Anderson DF, Wilson SJ, McGill JI, Church MK: Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms. J Allergy Clin Immunol. 2001 Sep;108(3):449-54. [PubMed:11544467 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tpr domain binding
Specific Function:
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with v...
Gene Name:
HSP90AA1
Uniprot ID:
P07900
Molecular Weight:
84659.015 Da
References
  1. Okada M, Itoh H, Hatakeyama T, Tokumitsu H, Kobayashi R: Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox. Biochem J. 2003 Sep 1;374(Pt 2):433-41. [PubMed:12803546 ]
  2. Nishikawa M, Takemoto S, Takakura Y: Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm. 2008 Apr 16;354(1-2):23-7. Epub 2007 Sep 29. [PubMed:17980980 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11