ethyl 4-{13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaen-2-ylidene}piperidine-1-carboxylate

• ChemBase ID: 338
• Molecular Formular: C22H23ClN2O2
• Molecular Mass: 382.88322
• Monoisotopic Mass: 382.14480567
• SMILES: Clc1cc2c(C(=C3CCN(CC3)C(=O)OCC)c3ncccc3CC2)cc1
• Canonical SMILES: CCOC(=O)N1CCC(=C2c3ccc(cc3CCc3c2nccc3)Cl)CC1
• InChI: InChI=1S/C22H23ClN2O2/c1-2-27-22(26)25-12-9-15(10-13-25)20-19-8-7-18(23)14-17(19)6-5-16-4-3-11-24-21(16)20/h3-4,7-8,11,14H,2,5-6,9-10,12-13H2,1H3
• InChIKey: JCCNYMKQOSZNPW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^3,^8]pentadeca-1(15),3(8),4,6,11,13-hexaen-2-ylidene}piperidine-1-carboxylate; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidine-1-carboxylate; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidine-1-carboxylate; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate
• IUPAC Traditional name: loratadine; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidine-1-carboxylate
• Brand Name: Aerotina; Alarin; Alavert; Alerpriv; Allertidin; Bedix Loratadina; Biloina; Bonalerg; Civeran; Claratyne; Clarinase; Clarinase Reperabs; Claritin; Claritin Reditabs; Claritin-D; Claritine; Clarityn; Clarityne; Fristamin; Histaloran; Lergy; Lertamine; Lesidas; Lisino; Loracert; Loradex; Loradif; Loranox; Lorantis; Lorastine; Loratyne; Loraver; Lorfast; Loritine; Lowadina; Nularef; Optimin; Polaratyne; Pylor; Restamine; Rhinase; Rinomex; Sanelor; Sensibit; Sinhistan Dy; Sohotin; Tadine; Talorat Dy; Velodan; Versal; Zeos; Lomilan; Roletra
• Synonyms: 4-(8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene-1-piperidinecarboxylic acid ethyl ester; Loratidine; Loratadine; ethyl 4-(8-chloro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(6H)-ylidene)piperidine-1-carboxylate; Loratadina [Spanish]; Loratadinum [Latin]; Loratadine; 4-(8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylic Acid Ethyl Ester; Claritin, Sch-29851,; Alavert; Claritin; Loratadine; Claritin-D; Claritine; Clarityn; Clarityne; Fristamin; ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate

Database IDs

• CAS Number: 79794-75-5
• MDL Number: MFCD00672869
• PubChem SID: 46507853; 160963801; 24278525
• PubChem CID: 3957

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 4.5269837
• LogD (pH = 7.4): 4.5542197
• Log P: 4.5545793
• Molar Refractivity: 116.9769 cm^3
• Polarizability: 41.254913 Å^3
• Polar Surface Area: 42.43 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.8
• LOG S: -4.46
• Solubility (Water): 1.34e-02 g/l

PROPERTIES

Physical Property

• Solubility: 0.000011 mg/ml; Acetonitrile; Chloroform; DMSO: soluble50 mg/mL; H2O: insoluble; Methanol
• Apperance: white powder; White Solid
• Melting Point: 134-136°C
• Hydrophobicity(logP): 3.8; 5.051

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Histamine receptors
• Gene Information: human ... CYP3A4(1576), HRH1(3269), KCNH1(3756), KCNH2(3757), PTAFR(5724)rat ... Hrh1(24448)
• Mechanism of Action: Histamine H1-receptor antagonist

Product Information

• Purity: ≥98% (HPLC); 95%; 98%
• Salt Data: Free Base
• Application(s): Other pharmacol. mechanisms under investigation; Used in the treatment of rhinitis and skin disorders
• Empirical Formula (Hill Notation): C22H23N2O2Cl

DETAILS

DrugBank - DB00455

• Drug Groups: approved
• Description: Loratadine is a derivative of azatadine and a second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (histamine H1 antagonists) it lacks central nervous system depressing effects such as drowsiness. [PubChem]
• Indication: A self-medication that is used alone or in combination with pseudoephedrine sulfate for the symptomatic relief of seasonal allergic rhinitis. Also used for the symptomatic relief of pruritus, erythema, and urticaria associated with chronic idiopathic urticaria in patients (not for children under 6 unless directed by a clincian).
• Pharmacology: Loratadine is a long acting second generation antihistamine that is similar in structure to cyproheptadine and azatadine. The pharmacology of loratadine is similar to other antihistamines, but unlike other H₁-blockers, loratidine is shown to exhibit competitive, specific, and selective antagonism of H₁ receptors. The exact mechanism of this interaction is unknown, but disposition of the drug suggests that loratadine's prolonged antagonism of histamine may be due to the drug's slow dissociation from the receptor or the formation of the active metabolite, desloratadine. Loratadine does not penetrate the CNS effectively and has a low affinity for CNS H₁-receptors.
• Toxicity: somnolence, tachycardia, and headache LD₅₀=mg/kg (orally in rat)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Rapidly absorbed following oral administration (40% bioavailability)
• Half Life: 8.4 hours
• Protein Binding: 97-99%
• References: See S: Desloratadine for allergic rhinitis. Am Fam Physician. 2003 Nov 15;68(10):2015-6. [Pubmed] ; Menardo JL, Horak F, Danzig MR, Czarlewski W: A review of loratadine in the treatment of patients with allergic bronchial asthma. Clin Ther. 1997 Nov-Dec;19(6):1278-93; discussion 1523-4. [Pubmed] ; Howarth PH: Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy. 1990 Aug;20 Suppl 2:31-41. [Pubmed] ; Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1358

Research Area: Inflammation
Biological Activity:
Loratadine is a selective inverse peripheral histamine H1-receptor agonist with an IC50 of >32 μM. [1] Histamine is responsible for many features of allergic reactions. Loratadine (Alavert, Claritin) is a second-generation antihistamine agent closely structurally related to tricyclic antidepressants such as imipramine, and distantly related to the atypical antipsychotic quetiapine, used to treat allergies. [2]

Sigma Aldrich - L9664

Biochem/physiol Actions
Non-sedating histamine H1-receptor antagonist.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. L9664.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - L469575

A nonsedating-type histamine H1-receptor.

REFERENCES

• See S: Desloratadine for allergic rhinitis. Am Fam Physician. 2003 Nov 15;68(10):2015-6. Pubmed
• Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. Pubmed
• Menardo JL, Horak F, Danzig MR, Czarlewski W: A review of loratadine in the treatment of patients with allergic bronchial asthma. Clin Ther. 1997 Nov-Dec;19(6):1278-93; discussion 1523-4. Pubmed
• Howarth PH: Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy. 1990 Aug;20 Suppl 2:31-41. Pubmed
• http://www.rxlist.com/claritin-drug.htm
• Bruttmann, G., et al.: J. Allergy Clin. Immunol., 83, 411 (1989)
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• Kreutner, W. et al., Allergy (Copenhagen), 1987, 42, 57, (pharmacol)
• Bradley, C.M. et al., Eur. J. Clin. Pharmacol., 1987, 32, 419, (pharmacol)
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• Schumacher, D.P. et al., J.O.C., 1989, 54, 2242, (synth, pmr)
• Piwinski, J.J. et al., J.O.C., 1990, 55, 3341, (metab)
• Piwinski, J.J. et al., J. Med. Chem., 1991, 34, 457, (activity)
• Barnett, A. et al., Chron. Drug Discovery, 1993, 3, 83, (rev)
• Roman, I.J. et al., Clin. Rev. Allergy, 1993, 11, 89, (pharmacol, rev)
• Haria, M. et al., Drugs, 1994, 48, 617, (rev)
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• Johnson, R. et al., J. Chromatogr., B: Biomed. Appl., 1994, 657, 125, (gc)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 8869, (synonyms)
• Caballero, R. et al., Br. J. Pharmacol., 1997, 122, 796-798, (desloratadine, pharmacol)
• Molet, S. et al., Clin. Exp. Allergy, 1997, 27, 1167-1174, (desloratadine, pharmacol)
• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 413
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• Barnett, A. et al., Agents Actions, 1984, 14, 590, (pharmacol)
• Pat. Coop. Treaty (WIPO), 1985, Schering, 85 03 707; CA, 104, 116091a, (desloratadine, synth, pharmacol)
• Villani, F.J. et al., Arzneim.-Forsch., 1986, 36, 1311, (synth)