Identification

Name
Nedocromil
Accession Number
DB00716  (APRD01137)
Type
Small Molecule
Groups
Approved, Investigational
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 IDs
FPL 59002
Product Ingredients
IngredientUNIICASInChI Key
Nedocromil sodiumET8IF4KS1T69049-74-7JQEKDNLKIVGXAU-UHFFFAOYSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlocrilLiquid2 %OphthalmicAllergan2000-02-29Not applicableCanada
AlocrilSolution / drops20 mg/mLOphthalmicAllergan2000-02-03Not applicableUs
MirezeLiquid2 %OphthalmicAllergan1997-08-062000-03-14Canada
TiladeAerosol, metered2 mgOralAventis Pharma Ltd.1998-12-062006-07-28Canada
Tilade Inhaler 2mg/aemAerosol, metered2 mgRespiratory (inhalation)Fisons1990-12-311999-08-13Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nedocromil SodiumSolution / drops20 mg/mLOphthalmicAkorn2012-09-10Not applicableUs
Categories
UNII
0B535E0BN0
CAS number
69049-73-6
Weight
Average: 371.3408
Monoisotopic: 371.100501903
Chemical Formula
C19H17NO7
InChI Key
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

Pharmacology

Indication

For the treatment of mild to moderate asthma

Structured Indications
Pharmacodynamics

Nedocromil 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 action

Nedocromil 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.

TargetActionsOrganism
ACysteinyl leukotriene receptor 1
suppressor
Human
ACysteinyl leukotriene receptor 2
antagonist
Human
UfMet-Leu-Phe receptor
antagonist
Human
UProstaglandin D2 receptor
unknown
Human
UHeat shock protein HSP 90-alphaNot AvailableHuman
Absorption

Low

Volume of distribution
Not Available
Protein binding

approximately 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 elimination

It is not metabolized and is eliminated primarily unchanged in urine (70%) and feces (30%).

Half life

~3.3 hours

Clearance
Not Available
Toxicity

Side 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

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

US4935244
General References
Not Available
External Links
Human Metabolome Database
HMDB0014854
KEGG Drug
D05129
KEGG Compound
C07255
PubChem Compound
50294
PubChem Substance
46507587
ChemSpider
45608
ChEBI
7492
ChEMBL
CHEMBL746
PharmGKB
PA450601
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nedocromil
ATC Codes
R03BC03 — NedocromilS01GX04 — NedocromilR01AC07 — Nedocromil
AHFS Codes
  • 52:02.00 — Antiallergic Agents
  • 48:92.00 — Respiratory Agents, Miscellaneous
FDA label
Download (362 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAsthma Bronchial1
3CompletedTreatmentAsthma Bronchial / Chronic Lung Diseases1

Pharmacoeconomics

Manufacturers
  • King pharmaceuticals inc
  • Allergan inc
  • Sanofi aventis us llc
Packagers
  • Allergan Inc.
  • Fisons PLC
  • King Pharmaceuticals Inc.
  • Rhone Poulenc Rorer Respiratory
  • Sanofi-Aventis Inc.
Dosage forms
FormRouteStrength
LiquidOphthalmic2 %
Solution / dropsOphthalmic20 mg/mL
Aerosol, meteredOral2 mg
Aerosol, meteredRespiratory (inhalation)2 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)
USRE38628No1992-08-222012-08-22Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)299 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
Chromenopyridines
Alternative Parents
Quinoline carboxylic acids / Chromones / Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Pyranones and derivatives / Benzenoids / Dicarboxylic acids and derivatives / Vinylogous amides / Heteroaromatic compounds
show 8 more
Substituents
Chromenopyridine / Quinoline-2-carboxylic acid / Chromone / Dihydroquinolone / Dihydroquinoline / Quinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Pyranone / Benzenoid
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterotricyclic compound, dicarboxylic acid (CHEBI:7492)

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, e...
Gene Name
CYSLTR1
Uniprot ID
Q9Y271
Uniprot Name
Cysteinyl leukotriene receptor 1
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, ind...
Gene Name
CYSLTR2
Uniprot ID
Q9NS75
Uniprot Name
Cysteinyl leukotriene receptor 2
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 ...
Gene Name
FPR1
Uniprot ID
P21462
Uniprot Name
fMet-Leu-Phe receptor
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 mobiliza...
Gene Name
PTGDR
Uniprot ID
Q13258
Uniprot Name
Prostaglandin D2 receptor
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. Under...
Gene Name
HSP90AA1
Uniprot ID
P07900
Uniprot Name
Heat shock protein HSP 90-alpha
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]

Drug created on June 13, 2005 07:24 / Updated on April 22, 2018 23:40