Loratadine

Bezeichnung:Loratadine

CAS-Nr79794-75-5

Englisch Name:Loratadine

CBNumberCB5283770

SummenformelC22H23ClN2O2

Molgewicht382.88

MOL-Datei79794-75-5.mol

Loratadine physikalisch-chemischer Eigenschaften

Schmelzpunkt	134-136°C
Siedepunkt	531.3±50.0 °C(Predicted)
Dichte	1.261±0.06 g/cm3(Predicted)
RTECS-Nr.	TM6129200
storage temp.	2-8°C
Löslichkeit	DMSO: 26 mg/mL, soluble
Aggregatzustand	powder
pka	4.27±0.20(Predicted)
Farbe	white
Wasserlöslichkeit	It is soluble in DMSO (50 mg/ml), ethanol (77 mg/ml at 25°C), water (<1 mg/ml at 25°C), chloroform, and methanol.
Merck	14,5578
BCS Class	2
Stabilität	Stable, but may be heat sensitive - refrigerate. Incompatible with strong oxidizing agents.
InChIKey	JCCNYMKQOSZNPW-UHFFFAOYSA-N
CAS Datenbank	79794-75-5(CAS DataBase Reference)
EPA chemische Informationen	1-Piperidinecarboxylic acid, 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-, ethyl ester (79794-75-5)

Sicherheit

Kennzeichnung gefährlicher	Xi
R-Sätze:	36/37/38
S-Sätze:	22-24/25-36-26
RIDADR	3077
WGK Germany	2
HS Code	29333990
Giftige Stoffe Daten	79794-75-5(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Loratadine Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S24/25:Berührung mit den Augen und der Haut vermeiden.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
Loratadine is a non-sedating antihistamine indicated for use in allergic rhinitis and chronic urticaria. Its major advantage over other non-sedating antihistamines such as astemizole and terfenadine is its very fast onset of action. Loratadine is claimed not to cross the blood-brain barrier.
Chemische Eigenschaften
White Crystalline Solid
Originator
Schering Plough (USA)
Verwenden
Histamine H1 receptor antagonist; antihistamine.
Verwenden
antinflammatory, analgesic, antipyretic
Verwenden
A nonsedating-type histamine H1-receptor
Verwenden
Loratadine, is used as a peripheral histamine H1 receptor agonist. It is also used as an orally active antiallergic agent. It is an important raw material and intermediate used in Organic Synthesis, Pharmaceuticals, Agrochemicals and Dyestuff.
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.
Definition
ChEBI: Loratadine is a benzocycloheptapyridine that is 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine substituted by a chloro group at position 8 and a 1-(ethoxycarbonyl)piperidin-4-ylidene group at position 11. It is a H1-receptor antagonist commonly employed in the treatment of allergic disorders. It has a role as a geroprotector, a H1-receptor antagonist, an anti-allergic agent and a cholinergic antagonist. It is an ethyl ester, a N-acylpiperidine, a tertiary carboxamide, an organochlorine compound and a benzocycloheptapyridine. It is functionally related to a desloratadine.
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).
Trademarks
Alavert (Wyeth); Claritin (Schering-Plough).
Therapeutic Function
Antihistaminic, Antiallergic
Allgemeine Beschreibung
Loratadine, 4-(8-chloro-5,6-dihydro-11Hbenzo[5,6]-cyclohepta[1,2-b]pyridin-l 1-ylidene-1-carboxylic acid ethyl ester, is a white to off-white powder insoluble in water but very soluble in acetone, alcohols, and chloroform. Loratadine is structurally related to the antihistamines azatadine and cyproheptadine, and to some tricyclic antidepressants. It differs from azatadine, in that a neutral carbamate group has replaced the basic tertiary amino moiety, and a phenyl ring has been substituted with a chlorine atom. Loratadine 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 displays potency comparable with that of astemizole and greater than that of terfenadine. Loratadine is indicated for the relief of nasal and nonnasal symptoms of seasonal allergic rhinitis. In the presence of a CYP3A4 inhibitor ketoconazole, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6.
Biologische Aktivität
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.
Pharmakokinetik
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.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly increased by erythromycin.
Antifungals: concentration of loratadine possibly increased by ketoconazole – avoid concomitant use.
Antivirals: concentration possibly increased by ritonavir.
Stoffwechsel
Loratadine undergoes an extensive first pass metabolism, mainly by CYP3A4 and CYP2D6. The major metabolite-desloratadine is pharmacologically active and responsible for a large part of the clinical effect. Approximately 40% of the dose is excreted in the urine and 42% in the faeces over a 10 day period and mainly in the form of conjugated metabolites. Approximately 27% of the dose is eliminated in the urine during the first 24 hours. Less than 1% of the active substance is excreted unchanged in the active form, as loratadine or desloratadine.
Lager
Store at RT
Dosage forms
10 mg daily. Patients with liver or renal impairment should be started on a lower dose.

Loratadine Upstream-Materialien And Downstream Produkte

Loratadine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

79794-75-5, Loratadine Verwandte Suche:

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