Desloratadine

Base Information

• Chemical Name: Desloratadine
• CAS No.: 100643-71-8
• Molecular Formula: C19H19ClN2
• Molecular Weight: 310.826
• Hs Code.: 2933399090
• European Community (EC) Number: 638-878-8
• NSC Number: 759824,675447
• UNII: FVF865388R
• DSSTox Substance ID: DTXSID1044196
• Nikkaji Number: J574.133E
• Wikipedia: Desloratadine
• Wikidata: Q418060
• NCI Thesaurus Code: C47474
• RXCUI: 275635
• Pharos Ligand ID: 55ATZ86HBSQJ
• Metabolomics Workbench ID: 43222
• ChEMBL ID: CHEMBL1172
• Mol file: 100643-71-8.mol

Synonyms:Neoclarityn;Opulis;Sch 34117;5H-Benzo[5,6]cyclohepta[1,2-b]pyridine,8-chloro-6,11-dihydro-11-(4-piperidinylidene)-;8-Chloro-11-(4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine;Aerius;Allex;Azomyr;Clarinex;Descarboethoxyloratadine;NSC675447;8-Chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine;

Chemical Property of Desloratadine

Chemical Property:

• Appearance/Colour: Beige solid
• Vapor Pressure: 6.25E-09mmHg at 25°C
• Melting Point: 150-151 °C
• Refractive Index: 1.625
• Boiling Point: 467.9 °C at 760 mmHg
• PKA: 10.27±0.20(Predicted)
• Flash Point: 236.8 °C
• PSA: 24.92000
• Density: 1.221 g/cm³
• LogP: 4.34770
• Storage Temp.: 2-8°C
• Solubility.: DMSO: >10mg/mL
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 310.1236763
• Heavy Atom Count: 22
• Complexity: 425

Purity/Quality:

99% ^*data from raw suppliers

Desloratadine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: C1CC2=C(C=CC(=C2)Cl)C(=C3CCNCC3)C4=C1C=CC=N4
• Recent ClinicalTrials: Fixed Dose Combination of DESloratadine / PREDnisolone in the Treat. of Moderate - Severe Allergic Rhinitis in Children
• Recent EU Clinical Trials: A prospective, multicenter, double-blind, placebo-controlled randomized study to assess efficacy and safety of LAIS? Grass pollen tablets in patients with seasonal grass pollen-induced allergic rhinoconjunctivitis
• Recent NIPH Clinical Trials: The effect of desloratadine on the urticariaresponse to the thermal stimuli.
• Description: Desloratadine is a second generation of tricyclic antihistamine. It is a H1-receptor antagonist which has anti-inflammatory activity. Its affinity to the H1 receptor is higher than most other H1-receptor antagonists. Desloratadine works by blocking a certain natural substance (histamine) which is produced during an allergic reaction. Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system. Desloratadine is used to treat nasal and non-nasal symptoms (watery eyes, runny nose, itching eyes/nose, sneezing, and itching) of seasonal allergic rhinitis. It is also used to relieve chronic itching caused by hives.
• Uses: Desloratadine has been used to test its effect on embryoid body development in in vitro gastrulation model of P19C5 stem cells. It has also been used as an antihistamine mimic in rats and to treat lung cancer (A549) and glioblastoma (U87) cells in various cellular studies. A histamine H1-receptor antagonist. An active metabolite of Loratadine Nonsedating-type histamine H1-receptor antagonist. An active metabolite of Loratadine. Also inhibits generation and release of inflammatory mediators from basophils and mast cells. antiinflammatory For 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.
• Indications: Desloratadine (Clarinex) is an active metabolite of loratadine. A 5 mg daily dose has been shown to be effective. There is no evidence that it offers any advantage over loratadine. Fexofenadine (like its parent compound terfenadine) may rarely promote cardiac arrhythmias (24). No significant difference in efficacy has been noted in the nonsedating H1 blockers. Combinations of nonsedating antihistamines in the morning and sedating antihistamines in the evening may be more cost effective than increasing doses of the nonsedating agent.
• Therapeutic Function: Antiallergic
• Clinical Use: Desloratadine was launched as an improved version of Schering-Plough's Claritin? (Loratadine), for the treatment of nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR). Desloratadine can be prepared by a 7-step synthesis starting with a Ritter reaction on 2-cyano-3-picoline and involving successively alkylation with 3- chlorobenzyl chloride, dehydration, Grignard reaction with the piperidine magnesium chloride, intramolecular cyclization in strong acidic medium, and finally demethylation of the piperidine. Desloratadine (the descarboethoxyloratadine) is a biologically active metabolite of the second-generation antihistamine Ioratadine. Desloratadine is a nonsedating competitive histamine H1 receptor antagonist with increased potency and improved safety as compared to Ioratadine. When compared with other H1 antagonists as an inhibitor of histamine-induced calcium flux in CHO cells, desloratadine was found to be more potent than most H1 antagonists (such as the widely used terfenadine, fexofenadine, cetirizine, Ioratadine and astemizole) in this assay. Desloratadine is also a potent antagonist of muscarinic M1 and M3 receptors (not M2) indicating anticholinergic activity. These effects may be the explanation for the unexpected decongestant effects of desloratadine reported in clinical trials. Desloratadine appears to be devoid of significant effects on potassium channels and does not appear to suffer from adverse interaction with cytochrome P450 inhibitors. Clinical studies have shown that it does not induce sedation or cardiac arrhythmias and does not potentiate the effects of alcohol. Apparent total body clearance is in the range of 114-201 l/h and the mean elimination half life is 19-34.6 h in human. Desloratadine is available as 5-mg tablets, which is the once-daily recommended dose for adults and children above 12 years. It may be taken without regard to food. The treatment not only improved symptoms of SAR but also improved patient ratings of nasal congestion. The FDA also has issued an "approvable" letter for this agent for the treatment of chronic idiopathic urticaria (ClU).

Technology Process of Desloratadine

There total 16 articles about Desloratadine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.4%

loratadine (79794-75-5) → descarboethoxyloratadine (100643-71-8)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; diethylamine; In tetrahydrofuran; at 50 ℃; for 4h; Temperature; Time; Concentration;

Reference yield: 63.0%

8-chloro-6,11-dihydro-11-(4-piperidinylydene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine carbon dioxide adduct → descarboethoxyloratadine (100643-71-8)

Guidance literature:

8-chloro-6,11-dihydro-11-(4-piperidinylydene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine carbon dioxide adduct; In ethanol; for 1h; Heating / reflux;

In methanol; acetone; Heating / reflux;

Reference yield:

N-methyldesloratadine (38092-89-6) → descarboethoxyloratadine (100643-71-8)

Guidance literature:

Multi-step reaction with 2 steps

1: Et₃N / toluene / Heating

2: aq. KOH / Heating

With potassium hydroxide; triethylamine; In toluene;

DOI:10.1021/jm00105a069

upstream raw materials:

loratadine

N-tert-butyl-3-methylpyridine-2-carboxamide

3-[2-(3-chlorophenyl)ethyl]-2-pyridine-carbonitrile

3-<2-(3-chlorophenyl)ethyl>-N-(1,1-dimethylethyl)-2-pyridinecarboxamide

Downstream raw materials:

[(R)-2-[4-(8-Chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidin-1-yl]-1-(4-methoxy-benzylsulfanylmethyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Refernces

• 1、 Mezei, Tibor,Volk, Balazs,Kiraly, Imre,Simig, Gyula. "A new addition compound of desloratadine with carbon dioxide". . p. 855 - 859. Retrieved 2008.
• 2、 -. "Desloratadine preparation method". Paragraph 0003. . Retrieved 2021/06/23.
• 3、 Lall, Manjinder S.,Bassyouni, Asser,Bradow, James,Brown, Maria,Bundesmann, Mark,Chen, Jinshan,Ciszewski, Gregory,Hagen, Anne E.,Hyek, Dennis,Jenkinson, Stephen,Liu, Bo,Obach, R. Scott,Pan, Senliang,Reilly, Usa,Sach, Neal,Smaltz, Daniel J.,Spracklin, Douglas K.,Starr, Jeremy,Wagenaar, Melissa,Walker, Gregory S.. "Late-Stage Lead Diversification Coupled with Quantitative Nuclear Magnetic Resonance Spectroscopy to Identify New Structure-Activity Relationship Vectors at Nanomole-Scale Synthesis: Application to Loratadine, a Human Histamine H1Receptor Inverse Agonist". . p. 7268 - 7292. Retrieved 2020/08/19.