79794-75-5 Usage
Uses
Loratadine is used as an antihistamine for the treatment of allergies. It works by blocking the H1 receptor, preventing the activation of cells by histamine, which is a chemical that causes many of the signs and symptoms of an allergy. This results in the relief of welts, itching, and tissue swelling associated with allergies.
Used in Pharmaceutical Industry:
Loratadine is used as an anti-inflammatory, analgesic, and antipyretic agent. It is also used as a nonsedating-type histamine H1-receptor antagonist, making it suitable for the treatment of allergic conditions without causing drowsiness.
Used in Organic Synthesis, Pharmaceuticals, Agrochemicals, and Dyestuff Industry:
Loratadine is used as a peripheral histamine H1 receptor agonist and as an orally active antiallergic agent. It is an important raw material and intermediate used in various chemical industries, including organic synthesis, pharmaceuticals, agrochemicals, and dyestuff.
Brand names:
Alavert (Wyeth) and Claritin (Schering-Plough) are some of the brand names under which Loratadine is sold.
Antiallergic
Loratadine is a common antiallergic medication, which is a second generation long-acting tricyclic antihistamine, rapid onset of action is strong, does not contain hormones, absorbed by the body metabolism with more active desloratadine, inhibiting histamine H1 receptor by competitively inhibit histamine-induced allergic symptoms, with? no obvious anticholinergic and central inhibition. It is used for the relief of clinical symptoms of allergic rhinitis related, such as sneezing, runny nose and nasal itching, eye itching and burning. It is also used to relieve symptoms of chronic urticaria and other allergic skin diseases.
Drug Interactions
Inhibition of hepatic drug-metabolizing enzyme function drugs can slow the metabolism of the product, such as itraconazole, ketoconazole, Daily with 400 mg ketoconazole suit, can make the product and its active metabolite to carboxyethyl loratadine increased plasma concentrations, but it was not observed in the changes of electrocardiogram (ECG). It can also inhibit the metabolism of loratadine when used with macrolides, cimetidine, theophylline and other drugs together.
Side effects
Common side effects include sleepiness, dry mouth, and headache. Serious side effects are rare and include allergic reactions, seizures, and liver problems. Use during pregnancy appears to be safe but has not been well studied. It is not recommended in children less than two years old. It is in the second-generation antihistamine family of medication.
Preparation
Compound (I) (0.05mo1) was dissolved in toluene (450m1), dropwise addition of ethyl chloroformate (0.15mo1). Canada finished in the sauna heating 2h, and then stirred at room temperature overnight. Added 800ml water. The benzene layer was separated, washed with water, and dried. Decompression concentrated oil, with petroleum ether after impregnation with acetonitrile, recrystallization, the yield of loratadine, 64%.
References
https://en.wikipedia.org/wiki/Loratadine
http://www.medicinenet.com/loratadine/article.htm
Indications
Loratadine (Claritin) is a long-acting, potent peripheral H1 blocker with minimal
sedative effects. It does not appear to have the same adverse cardiac effects as
the other nonsedating H1 antihistamines. It is indicated for allergic rhinitis and
chronic urticaria.
Manufacturing Process
Preparation of Loratadine In a two-liter vessel provided with a thermometer, a reflux condenser and nitrogen atmosphere, dry tetrahydrofuran (343 ml) was placed, and cooled between 0 and -5°C. Titanium tetrachloride (28.5 ml, 49.5 g, 0.255 mol) was slowly added with stirring (17 min.), keeping the temperature in the above indicated range, a yellow suspension being formed. After the addition was finished, stirring was continued for 10 min. Then, zinc dust (34.5 g, 0.524 mol) was added with stirring in approximately 15 min. keeping the temperature in the above cited range, and after addition was finished, stirring was continued at this temperature for 20 min., a blue suspension being formed. Then, pyridine (17 ml, 0.21 mol) was added with stirring, keeping the temperature in the above range, and then, a solution of 8-chloro-5,6- dihydrobenzo[5,6]cyclohepta[1,2-b]pyridin-11-one (30.0 g, 0.123 mol) and ethyl 4-oxopiperidine-1-carboxylate (25.2 g, 0.147 mol) in anhydrous tetrahydrofuran (96 ml) was added in about 20 min., with stirring and keeping the temperature in the above cited range. The, thus obtained, dark brown mixture was stirred for 3 h keeping the temperature in the above cited range, then was allowed to heat to room temperature and kept at this temperature for 2 h and then heated to 40°C for 17 h. The tetrahydrofuran was distilled off
from the reaction mixture to give a black resin that was dissolved in
dichloromethane (300 ml) and acidified by addition of isopropanol/HCl 7.2 N
(97 ml). The mixture was stirred for 10 min, and the phases were separated,
being the aqueous one extracted with dichloromethane (150 ml). The
combined organic phases were washed 6 times with a mixture of water (125
ml) and 35% aqueous HCl (7.5 ml). Then, the organic phase was basified to
pH 7.5-8.0 by addition of 30% aqueous NH3. The mixture was stirred for 10
min and the phases were separated, and then washed 3 times with water
(250 ml). The organic phase was dried with anhydrous sodium sulfate, filtered
and the solvent eliminated in vacuo to give a residue (47.47 g) that was
treated with acetonitrile (97 ml). The solid was filtered and crystallized from
the same solvent to give pure Loratadine, m.p. 132-133°C (18.8 g, 40%
yield).
Biological Activity
Peripheral histamine H 1 receptor antagonist (K i = 35 nM); devoid of central effects. Orally active antiallergic agent.
Biochem/physiol Actions
Non-sedating histamine H1-receptor antagonist.
Pharmacokinetics
Good oral absorption, rapid and extensive metabolism in the liver, and excreted by urine and feces. After taking the medicine, the effect is fast, and some patients show the effect within 30 minutes. Tmax is 1.5 ~ 2 h, and the elimination half-life is 8 ~ 14 h. The half-life of the active metabolite decarboxymethylethoxyloratadine (DCL) is 17 ~ 24h. The half-life of the elderly and patients with liver disease may be longer. The binding rate of loratadine to plasma protein was 97% ~ 99%, and DCL was 73% ~ 76%. After 24 hours, about 27% of loratadine was excreted from urine, about 40% was eliminated from urine and 42% was excreted from stool after 10 days. With less milk secretion, it is safe to use drugs during lactation.
Clinical Use
Loratadine is related to the first-generation tricyclic antihistamines and to
antidepressants. It is nonsedating, and neither it nor its major metabolite, desloratadine
(descarboethoxyloratadine), is associated with the potentially cardiotoxic effects reported for
terfenadine and astemizole. On chronic dosing, the AUC (plasma concentration–time curve)
for the metabolite is greater than that for the parent drug, and its half-life is longer.
Drug interactions
Molecular weight (daltons) 382.9 % Protein binding 97-99 % Excreted unchanged in urine 40 Volume of distribution (L/kg) No data Half-life - normal/ESRF (hrs) 12-15 / Unchanged
Metabolism
Molecular weight (daltons) 382.9 % Protein binding 97-99 % Excreted unchanged in urine 40 Volume of distribution (L/kg) No data Half-life - normal/ESRF (hrs) 12-15 / Unchanged
Dosage forms
10 mg daily. Patients with liver or renal impairment should be
started on a lower dose.
Check Digit Verification of cas no
The CAS Registry Mumber 79794-75-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,9,7,9 and 4 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 79794-75:
(7*7)+(6*9)+(5*7)+(4*9)+(3*4)+(2*7)+(1*5)=205
205 % 10 = 5
So 79794-75-5 is a valid CAS Registry Number.
InChI:InChI=1/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
79794-75-5Relevant articles and documents
Preparation method of loratadine
-
, (2021/02/10)
The invention provides a preparation method of loratadine. The method comprises the following steps: taking 2-cyano-3-methylpyridine as a raw material, and carrying out Ritter reaction, m-chlorobenzylchloride condensation, POCl3 deprotection group, Grignard reaction, cyclization and ethyl chloroformate substitution to obtain 4(8-chlorine-5, 6-dihydro-11H-benzo-[5, 6]cycloheptano[1, 2-b]pyridine-11-subunit)-1-piperidine carboxylic acid ethyl ester. According to the invention, a post-treatment process is innovated, and a new cyclization system is adopted to catalyze the reaction, so that the use of high-cost and high-toxicity strong acid is avoided, and a milder and more economical synthesis method is provided for industrial production.
Non-innocent Radical Ion Intermediates in Photoredox Catalysis: Parallel Reduction Modes Enable Coupling of Diverse Aryl Chlorides
Chernowsky, Colleen P.,Chmiel, Alyah F.,Wickens, Zachary K.,Williams, Oliver P.,Yeung, Charles S.
supporting information, p. 10882 - 10889 (2021/07/31)
We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl radical coupling reactions from abundant but difficult to reduce aryl chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled by a key terminal reductant byproduct, carbon dioxide radical anion.
NEW PROCESS FOR PREPARING LORATADINE FROM A KETONE INTERMEDIATE
-
Page/Page column 9, (2015/06/18)
This application is directed to a last step synthetic process for making loratadine from ketone intermediate.
Loratadine and analogues: Discovery and preliminary structure-activity relationship of inhibitors of the amino acid transporter B0AT2
Cuboni, Serena,Devigny, Christian,Hoogeland, Bastiaan,Strasser, Andrea,Pomplun, Sebastian,Hauger, Barbara,H?fner, Georg,Wanner, Klaus T.,Eder, Matthias,Buschauer, Armin,Holsboer, Florian,Hausch, Felix
supporting information, p. 9473 - 9479 (2015/01/09)
B0AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B0AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family. Reversible inhibition of B0AT2 was confirmed by electrophysiology. A series of loratadine analogues were synthesized to gain insight into the structure-activity relationships. Our studies provide the first chemical tool for B0AT2.
Design and synthesis of thiourea derivatives containing a benzo[5,6]cyclohepta[1,2-b]pyridine moiety as potential antitumor and anti-inflammatory agents
Liu, Wukun,Zhou, Jinpei,Zhang, Tong,Zhu, Haiyang,Qian, Hai,Zhang, Huibin,Huang, Wenlong,Gust, Ronald
, p. 2701 - 2704 (2012/05/20)
Thiourea derivatives (6a-e) were developed and screened for antitumor and anti-inflammatory activity. Most of the compounds exhibited growth inhibitory effects comparable to 5-fluorouracil in vitro against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. They also showed stronger anti-inflammatory activity than ibuprofen in vivo in the xylene-induced ear swelling assay in mice.
PREPARATION OF LORATADINE FORM I
-
Page/Page column 4-5, (2008/12/07)
A process for preparing loratadine crystalline polymorphic Form I.
PROCESS FOR THE PREPARATION OF DESLORATADINE POLYMORPH MIXTURES
-
Page/Page column 4-5, (2008/12/09)
The present application provides a process for the preparation of mixture of polymorphic Form I and Form II of desloratadine in any desired ratio.
A PROCESS FOR THE MANUFACTURING OF LORATADINE AND ITS INTERMEDIATES
-
Page/Page column 17, (2010/02/15)
The process comprises (i) subjecting substituted benzyl halide to cyanation in a biphasic system using water immiscible solvents by any known methods, (ii) condensing in situ the phenyl acetonitrile thus obtained with nicotinic ester in presence of alkali metal alkoxide and water immiscible organic solvent to produce ketonitrile, (iii) hydrolyzing followed by decarboxylating the said ketonitrile in situ to respective ketone in acid environment below 60° C, (iv) subjecting the ketone so obtained to reduction followed by N-oxidation, cyanation, and hydrolysis by any known methods to produce picolinic acid, (v) cyclising the said picolinic acid to tricyclic ketone by conventional methods, (vi) treating the said tricyclic ketone with organometallic compound containing Mg to produce carbinol, (viii) purifying the said carbinol with purifying agent selected from polar water miscible organic solvent followed by dehydrating with neat sulphuric acid at the temperature below 50° C, to get N-methyl product (olefin), and subjecting the said olefin to N-carbethoxylation to produce loratadine. Loratadine can also be prepared by treating cayano compound with organometallic compound containing Mg to produce a ketone by the methods known in the art followed by cyclising in presence of a mixture of sulfuric acid and a source of boric acid to get N-methyl product and converting to loratadine by N-carbethoxylation.
PROCESS FOR THE PREPARATION OF LORATADINE
-
Page 9, (2008/06/13)
A process for the production of loratadine chemically known as 8-chloro-11-(1-ethoxycarbonyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptal[1,2-B]pyridene has been described. The process comprises reacting a tri-cyclic aromatic ketone with an organometallic compound containing Mg in presence of organic solvent then hydrolyzing and isolating loratadine by conventional methods wherein the reaction between cyclic ketone and the said organometallic compound is effected at a glacial temperature.
PROCESS FOR PREPARING TRICYCLIC COMPOUNDS HAVING ANTIHISTAMINIC ACTIVITY
-
, (2008/06/13)
Disclosed is a process for preparing a compound having formula (I) wherein R is selected from the group consisting of: alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, and cycloalkyalkyl, R being optionally substituted by substituents selected from halo, -OH, alkyl, alkoxy, or -CF3, said process comprising the following steps: (a) reacting a ketone having formula (A) with a carbanion having formula (B) wherein R is defined above, and R and R are independently selected from the group consisting of -OR and -R; wherein R is alkyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, or substituted cycloalkylalkyl; (b) treating the reaction mixture from step (a) with a protonating agent to form a beta -hydroxy intermediate having formula (C) wherein R, R and R are as defined above; and (c) thermally decomposing the beta -hydroxy intermediate to form the compound of formula (I). The compounds made by this process have antihistaminic activity, e.g., loratadine. Also disclosed is a process for preparing descarboethoxyloratadine, by carrying out the process above, and converting the product to descarboethoxyloratadine. Also disclosed are novel intermediates having formula (II) and (III) wherein R, R and R are as defined above.
