Desloratadine (T3D4557)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-08-30 21:04:00 UTC
Update Date2014-12-24 20:26:52 UTC
Accession NumberT3D4557
Identification
Common NameDesloratadine
ClassSmall Molecule
DescriptionDesloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.
Compound Type
  • Amine
  • Cholinergic Antagonist
  • Drug
  • Histamine Antagonist
  • Histamine H1 Antagonist, Non-Sedating
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
8-Chloro-11-piperidin-4-ylidene-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
8-chloro-6,11-dihydro-11-(4-Piperidinylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridine
Aerius
Claramax
Clarinex
Descarboethoxyloratadine
DESLORATADINE
NeoClarityn
Chemical FormulaC19H19ClN2
Average Molecular Mass310.821 g/mol
Monoisotopic Mass310.124 g/mol
CAS Registry Number100643-71-8
IUPAC Name13-chloro-2-(piperidin-4-ylidene)-4-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaene
Traditional Nameclarinex
SMILESClC1=CC=C2C(CCC3=C(N=CC=C3)C2=C2CCNCC2)=C1
InChI IdentifierInChI=1S/C19H19ClN2/c20-16-5-6-17-15(12-16)4-3-14-2-1-9-22-19(14)18(17)13-7-10-21-11-8-13/h1-2,5-6,9,12,21H,3-4,7-8,10-11H2
InChI KeyInChIKey=JAUOIFJMECXRGI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzocycloheptapyridines
Sub ClassNot Available
Direct ParentBenzocycloheptapyridines
Alternative Parents
Substituents
  • Benzocycloheptapyridine
  • Aryl chloride
  • Aryl halide
  • Piperidine
  • Pyridine
  • Benzenoid
  • Heteroaromatic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Azacycle
  • Amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogP3.2
Predicted Properties
PropertyValueSource
Water Solubility0.004 g/LALOGPS
logP3.48ALOGPS
logP3.97ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)9.73ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area24.92 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.04 m³·mol⁻¹ChemAxon
Polarizability34.35 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00pm-1090000000-22109c83f6d7364ec27f2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-08fr-0095000000-2816aba50d0b94d568cf2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-08fr-0095000000-5b3f7555b72461661fa12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0940000000-d20368a648c20c37e1a02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-08fr-0095000000-2816aba50d0b94d568cf2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0940000000-9a0f5f4d81f4c42c85bb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-08fr-0095000000-5b3f7555b72461661fa12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0bt9-0094000000-536b5a1d05f7479c2b042017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-4cdd75cfb5b6a95978ee2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0a4i-0091000000-702ea1b0afc5802588fe2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-08fr-0094000000-5d18c689b0d8db209b612021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0a4i-0090000000-0a46374188b55ae72bbb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0bt9-0094000000-c7895278fdf48ea14ae72021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0090000000-8a8858c86845b74e96f32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-0a4l-0090000000-fe6da9796038e735965f2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0019000000-1fb53cf6a1a948b666162016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-5098000000-08255511bea5c886b9102016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9040000000-e8c991ebd37a0b0c25442016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-3a9994f7ccd4384824612016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-1029000000-5f479948c9e9c3620d412016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-007p-5190000000-6fbaf13ffa17c703d90d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-c678c7bde266b8b7c5612021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0009000000-40e78516a505b8e5b66e2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6s-0190000000-d26af4a5ad57450875ac2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-3adde6a718d7e97498aa2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-053r-9005000000-07072a7bbfb51b9420542021-10-11View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityLike other H1-blockers, Desloratadine competes with free histamine for binding at H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.
Metabolism Route of Elimination: Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. Approximately 87% of a 14C-desloratadine dose was equally recovered in urine and feces. Half Life: 50 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the relief of symptoms of seasonal allergic rhinitis, perennial (non-seasonal) allergic rhinitis. Desloratidine is also used for the sympomatic treatment of pruritus and urticaria (hives) associated with chronic idiopathic urticaria.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00967
HMDB IDNot Available
PubChem Compound ID124087
ChEMBL IDCHEMBL1172
ChemSpider ID110575
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID291342
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDesloratadine
References
Synthesis Reference

Zoltan Toth, “Processes for preparation of polymorphic forms of desloratadine.” U.S. Patent US20040242619, issued December 02, 2004.

MSDST3D4557.pdf
General References
  1. Mann RD, Pearce GL, Dunn N, Shakir S: Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice. BMJ. 2000 Apr 29;320(7243):1184-6. [10784544 ]
  2. Glass DJ, Harper AS: Assessing satisfaction with desloratadine and fexofenadine in allergy patients who report dissatisfaction with loratadine. BMC Fam Pract. 2003 Aug 13;4:10. Epub 2003 Aug 13. [12917016 ]
  3. See S: Desloratadine for allergic rhinitis. Am Fam Physician. 2003 Nov 15;68(10):2015-6. [14655812 ]
  4. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. [18336052 ]
  5. Bachert C: A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis. Clin Ther. 2009 May;31(5):921-44. doi: 10.1016/j.clinthera.2009.05.017. [19539095 ]
  6. DuBuske L: Desloratadine for chronic idiopathic urticaria: a review of clinical efficacy. Am J Clin Dermatol. 2007;8(5):271-83. [17902729 ]
  7. Bachert C, Maurer M: Safety and efficacy of desloratadine in subjects with seasonal allergic rhinitis or chronic urticaria: results of four postmarketing surveillance studies. Clin Drug Investig. 2010;30(2):109-22. doi: 10.2165/11530930-000000000-00000. [20067329 ]
  8. Simons FE, Prenner BM, Finn A Jr: Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2003 Mar;111(3):617-22. [12642846 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histamine H1 receptor
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00097 uMNot AvailableBindingDB 50073179
References
  1. Wu RL, Anthes JC, Kreutner W, Harris AG, West RE Jr: Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor. Int Arch Allergy Immunol. 2004 Dec;135(4):313-8. Epub 2004 Nov 24. [15564772 ]
  2. Cieslewicz G, Gondorowicz K, Grzelewska-Rzymowska I, Rozniecki J: [Effect of loratadine, selective antagonist of histamine H1 receptors, on histamine-induced bronchoconstriction]. Pneumonol Alergol Pol. 1995;63(5-6):281-5. [7581058 ]
  3. Letari O, Miozzo A, Folco G, Belloni PA, Sala A, Rovati GE, Nicosia S: Effects of loratadine on cytosolic Ca2+ levels and leukotriene release: novel mechanisms of action independent of the anti-histamine activity. Eur J Pharmacol. 1994 Feb 15;266(3):219-27. [8174605 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  5. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. [18336052 ]
  6. DuBuske L: Desloratadine for chronic idiopathic urticaria: a review of clinical efficacy. Am J Clin Dermatol. 2007;8(5):271-83. [17902729 ]
  7. Simons FE, Prenner BM, Finn A Jr: Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2003 Mar;111(3):617-22. [12642846 ]
  8. Dhanya NB, Thasleem Z, Rai R, Srinivas CR: Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug;74(4):361-3. [18797058 ]
  9. Lewis TA, Young MA, Arrington MP, Bayless L, Cai X, Collart P, Eckman JB, Ellis JL, Ene DG, Libertine L, Nicolas JM, Scannell RT, Wels BF, Wenberg K, Wypij DM: Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4. [15482930 ]
Target Details
2. Multidrug resistance protein 1
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5043 uMNot AvailableBindingDB 50073179
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Evaluation of the interaction of loratadine and desloratadine with P-glycoprotein. Drug Metab Dispos. 2001 Aug;29(8):1080-3. [11454724 ]
Target Details
3. Protein farnesyltransferase subunit beta
General Function:
Zinc ion binding
Specific Function:
Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
Gene Name:
FNTB
Uniprot ID:
P49356
Molecular Weight:
48773.2 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>65 uMNot AvailableBindingDB 50073179
References
  1. Cooper AB, Strickland CL, Wang J, Desai J, Kirschmeier P, Patton R, Bishop WR, Weber PC, Girijavallabhan V: Synthesis of 5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidine-N-cy anoguanidine derivatives as inhibitors of ras farnesyl protein transferase. Bioorg Med Chem Lett. 2002 Feb 25;12(4):601-5. [11844681 ]