Levocetirizine

Base Information

• Chemical Name: Levocetirizine
• CAS No.: 130018-77-8
• Molecular Formula: C21H25ClN2O3
• Molecular Weight: 388.894
• Hs Code.: 29335990
• UNII: 6U5EA9RT2O
• DSSTox Substance ID: DTXSID60156294
• Nikkaji Number: J1.370.778B
• Wikipedia: Levocetirizine
• Wikidata: Q421091
• NCI Thesaurus Code: C66008
• RXCUI: 356887
• Pharos Ligand ID: 5XY1M5TZ3VDY
• Metabolomics Workbench ID: 149722
• ChEMBL ID: CHEMBL1201191
• Mol file: 130018-77-8.mol

Synonyms:(2-(4-((R)-(4-chlorophenyl)phenylmethyl)piperazin-1-yl)ethoxy)acetic acid dihydrochloride;(2-(4-((R)-p-chloro-alpha-phenylbenzyl)-1-piperazinyl)ethoxy)acetic acid;acetic acid, (2-(4-((R)-(4-chlorophenyl)phenylmethyl)-1-piperazinyl)ethoxy)-;acetic acid, (2-(4-((R)-(4-chlorophenyl)phenylmethyl)-1-piperazinyl)ethoxy)-, dihydrochloride;cetirizine (R)-form dihydrochloride;levocetirizine;levocetirizine dihydrochloride;levocetirizine hydrochloride;levocetrizine;UCB-28556;Xusal;Xyzal

Chemical Property of Levocetirizine

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 1.39E-12mmHg at 25°C
• Melting Point: 205-208°C (dec.)
• Boiling Point: 542.1 °C at 760 mmHg
• PKA: 3.46±0.10(Predicted)
• Flash Point: 281.6 °C
• PSA: 53.01000
• Density: 1.237 g/cm³
• LogP: 3.02400
• Storage Temp.: -20°C Freezer
• XLogP3: 1.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 388.1553704
• Heavy Atom Count: 27
• Complexity: 443

Purity/Quality:

99% ^*data from raw suppliers

Levocetirizine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CN(CCN1CCOCC(=O)O)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl
• Isomeric SMILES: C1CN(CCN1CCOCC(=O)O)[C@H](C2=CC=CC=C2)C3=CC=C(C=C3)Cl
• Recent ClinicalTrials: A Phase I Study of LY3471851 in Healthy Participants
• Recent EU Clinical Trials: Efficacy and safety of levocetirizine alone or in combination with tranexamic acid in the treatment of spontaneous chronic urticaria. Multicentric controlled randomized study in cross-over, double-blind.
• Recent NIPH Clinical Trials: Research on effect of hay fever drugs on brain functions
• Description: The (R)-enantiomer of the second-generation antihistamine cetirizine, levocetirizine, was first introduced in Germany for seasonal allergic rhinitis (including ocular symptoms), perennial allergic rhinitis and chronic idiopathic urticaria. The dihydrochloride salt can be prepared in four steps from optically active 4-chlorobenzhydrylamine obtained by resolution of its racemate with (+)-tartaric acid. Levocetirizine (eutomer) is a 2-fold more potent H1 antagonist than cetirizine whereas the other enantiomer (distomer) is 10-fold less potent compared to levocetirizine. Pharmacodynamic studies on healthy volunteers showed that compared to cetirizine, half the dose of levocetirizine (5 mg) was necessary to obtain similar inhibitory effects in the skin test of histamine-induced wheal and flare as well as on histamine-induced nasal congestion and nasal resistance. There was no evidence of chiral inversion of levocetirizine in vivo in several species including human. The daily dose of drug is rapidly and extensively absorbed in human. Interestingly, its volume of distribution (0.41 kg/L) is smaller than that of the distomer (0.60 kg/L). The low volume of distribution is considered as favorable for an antihistamine both in terms of efficacy and safety. Due to its high metabolic stability and lack of effect on the activities of the major CYP isoenzymes, levocetirizine is unlikely to cause interactions with other administered drugs. No clinically relevant effect on electrocardiograms of healthy volunteers was detected.
• Uses: A nonsedating type histamine H1-receptor antagonist. A major metabolite of Hydroxyzine. Pharmacological activity resides primarily in the (R)-isomer. Antihystaminic. H1 antihistamine, antiallergic Labeled cetirizine, intended for use as an internal standard for the quantification of cetirizine by GC- or LC-mass spectrometry.

Technology Process of Levocetirizine

There total 23 articles about Levocetirizine 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: 90.0%

C23H29ClN2O3 (246870-46-2) → levocetirizine (130018-77-8)

Guidance literature:

With lithium hydroxide; In tetrahydrofuran; methanol; water; at 65 ℃; for 2h;

Reference yield: 86.5%

(2-chloroethoxy)-acetic acid (14869-41-1) + (R)-1-((4-chlorophenyl)(phenyl)methyl)piperazine (300543-56-0) → levocetirizine (130018-77-8)

Guidance literature:

With tetrabutylammomium bromide; sodium hydride; In N,N-dimethyl-formamide; at 95 ℃; for 5h; Inert atmosphere;

Reference yield: 74.0%

(R)-(2-{4-[(4-chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetic acid methyl ester → levocetirizine (130018-77-8)

Guidance literature:

With hydrogenchloride; In water; enantioselective reaction; Large scale;

DOI:10.1021/op0002951

upstream raw materials:

(R)-2-(2-{4-[(4-chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetamide

(+)-[2-[4-[(4-chlorophenyl)-phenyl methyl]-1-piperazinyl]]ethanol

sodium monochloroacetic acid

(R)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]-1-(S)-[N-(1-phenyIethyl)]acetamide

Downstream raw materials:

(+)-Cetirizine dihydrochloride

levocetirizine dihydrochloride

Refernces

• 1、 Chmielewska, Aleksandra,Konieczna, Lucyna,Baczek, Tomasz. "A novel two-step liquid-liquid extraction procedure combined with stationary phase immobilized human serum albumin for the chiral separation of cetirizine enantiomers along with M and P parabens". . . Retrieved 2016.
• 2、 -. "Preparation method of levocetirizine". Paragraph 0024; 0028. . Retrieved 2020/06/17.