79794-75-5 Usage
Description
Loratadine is a non-sedating antihistamine indicated for use in allergic rhinitis and chronic urticaria. It is a white crystalline solid that is insoluble in water but very soluble in acetone, alcohols, and chlorform. Loratadine is structurally related to the antihistamines azatadine and cyproheptadine, and to some tricyclic antidepressants. It is a selective peripheral H1-antihistamine with a receptor-binding profile like that of the other members of this series, except that it has more antiserotonergic activity. Thus, it produces no substantial CNS or autonomic side effects or cardiac toxicity. Loratadine is indicated for the relief of nasal and nonnasal symptoms of seasonal allergic rhinitis and is claimed not to cross the blood-brain barrier.
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
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Paragraph 0029; 0058-0064, (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.
NEW PROCESS FOR PREPARING LORATADINE FROM A KETONE INTERMEDIATE
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Page/Page column 9, (2015/06/18)
This application is directed to a last step synthetic process for making loratadine from ketone intermediate.
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
experimental part, 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.