Loteprednol etabonate

Bezeichnung:Loteprednol etabonate

CAS-Nr82034-46-6

Englisch Name:Loteprednol etabonate

CBNumberCB9396463

SummenformelC24H31ClO7

Molgewicht466.95

MOL-Datei82034-46-6.mol

Loteprednol etabonate physikalisch-chemischer Eigenschaften

Schmelzpunkt	220.5-223.5
Siedepunkt	600.1±55.0 °C(Predicted)
Dichte	1.31±0.1 g/cm3(Predicted)
storage temp.	-20°C
Löslichkeit	DMSO: soluble5mg/mL, clear (warmed)
Aggregatzustand	powder
pka	14.06±0.70(Predicted)
Farbe	white to beige
Wasserlöslichkeit	<1mg/L(23 ºC)
Stabilität	Hygroscopic
InChIKey	DMKSVUSAATWOCU-ICASLIHPSA-N

Sicherheit

WGK Germany	3
HS Code	2937.22.0000

Gefahreninformationscode (GHS)

Loteprednol etabonate Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Loteprednol etabonate was introduced in the US as Lotemax (opththalmic suspension at 0.5%) for the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the ocular globe, and as Alrex (opththalmic suspension at 0.2%) for the symptomatic treatment of seasonal allergic conjunctivitis. Loteprednol etabonate is a novel soft corticosteroid with a superior efficacy and an improved safety profile compared to prior ophthalmic steroids due to its metabolic lability and a fast enzymatic transformation to inactive metabolite. A combination of Lotemax with the antibiotic Tobramycin is currently under development.
Chemische Eigenschaften
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Originator
Pharmos (US)
Verwenden
An ophthalmic corticosteroid. Used as an anti-inflammatory.
Verwenden
Biological Activity Chemical Information Tech Support & FAQs Biological Activity Loteprednol etabonate is an anti-inflammatory corticosteroid used in ophthalmology. It is used for the treatment of steroid responsive inflammatory conditions of the eye su
Definition
ChEBI: Loteprednol etabonate is an etabonate ester, an 11beta-hydroxy steroid, a steroid ester, an organochlorine compound, a steroid acid ester and a 3-oxo-Delta(1),Delta(4)-steroid. It has a role as an anti-inflammatory drug. It is functionally related to a loteprednol.
Manufacturing Process
To a solution of hydrocortisone (15 g, 0.04 mol) in 120 ml of THF and 30 ml of methanol at room temperature is added a warm solution of sodium metaperiodate (25.7 g, 0.12 mol) in 100 ml of water. The reaction mixture is stirred at room temperature for 2 hours, then is concentrated under reduced pressure to remove the tetrahydrofuran and methanol. The solid is triturated with 50 ml of water, separated by filtration, washed with water and dried in vacuo at 50°C for 3 hours. The product, 11β,17α-dihydroxyandrost-4-en-3- one-17β-carboxylic acid (i.e., cortienic acid), is obtained in approximately 96% yield (13.76 g); melting point 231-234°C.
To a cold solution of 11β,17α-dihydroxyandrost-4-en-3-one-17β-carboxylic acid (5% weight/volume; 1 mol) and triethylamine (4 mol) in dichloromethane is added a 50% (weight/volume) solution of ethyl chloroformate (3.9 mol) in dichloromethane. The reaction mixture is allowed to warm to room temperature over a 2 hour period. The triethylamine hydrochloride precipitate which forms is removed by filtration and the filtration is washed successively with 3% sodium bicarbonate, 1% hydrochloric acid and water. The organic layer is separated, dried with magnesium sulfate, and filtered. The filtrate is concentrated in vacuo to a foam.
The foam is used in the next step below or chromatographed and crystallized for analysis. The product 17α-ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3- one-17β-carboxylic acid, melting at 192-195°C C after chromatography and crystallization.
17α-Ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylic acid is combined with an equivalent amount of 1 N sodium hydroxide in methanol and that solution is diluted to 100 times the original volume with ethyl ether. The suspension which results is refrigerated for 1 hour. Then, the crystals which form are removed by filtration, dried in an evacuated desiccator, and dissolved in hexamethylphosphoramide (10% weight/volume). A portion of the resultant solution containing 1 mole of the acid salt, i.e. of sodium 17αethoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylate, is combined with 4 moles of chloromethyl iodide. The reaction mixture is maintained at room temperature for 3 hours, then is diluted to 10 times the original volume with ethyl acetate. The diluted reaction mixture is washed successively with 5% sodium thiosulfate, 3% sodium bicarbonate, and water. The organic layer is separated, dried with magnesium sulfate and filtered. The filtrate is concentrated in vacuo to a foam. The foam is purified by crystallization from ethyl ether or tetrahydrofuran/hexane. There is thus obtained chloromethyl-17α-ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3- one-17β-carboxylate, melting at 197-200°C after crystallization.
Trademarks
Alrex (Bausch & Lomb); Lotemax (Bausch & Lomb); Lotemax (Pharmos);Lotemax (0.5%）.
Therapeutic Function
Glucocorticoid
Allgemeine Beschreibung
Loteprednol etabonate,chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17-carboxylate (Alrex,Lotemax), has a modified carboxylate at the C17 positionrather than the typical ketone functionality. This modificationmaintains affinity for the GR but allows facile metabolismto inactive metabolites. This limits the systemic actionof the drug. Loteprednol etabonate is used as anophthalmic suspension that has greatly reduced systemicaction because of rapid metabolism to the inactive carboxylate.
Biochem/physiol Actions
Loteprednol Etabonate is an anti-inflammatory corticosteroid (ophthalmology).

Loteprednol etabonate Upstream-Materialien And Downstream Produkte

Loteprednol etabonate Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

82034-46-6, Loteprednol etabonate Verwandte Suche:

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