82034-46-6 Usage
Description
Loteprednol etabonate is a potent topical anti-inflammatory corticosteroid, specifically designed for ophthalmic use. It features a 17α-chloromethyl ester and a 17β-etabonate group, which contribute to its high lipophilicity and strong affinity for the glucocorticoid receptor. Loteprednol etabonate is rapidly metabolized into inactive metabolites, ensuring a favorable safety profile.
Used in Ophthalmology:
Loteprednol etabonate is used as an ophthalmic corticosteroid for the treatment of steroid-responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitis. It is also used in ophthalmic ointment form for post-operative inflammation and pain relief following ocular surgery.
Used in Allergy Management:
As a nasal spray, loteprednol etabonate is used for the treatment and management of seasonal allergic rhinitis, providing relief from inflammation and associated symptoms.
Used in Combination Therapy:
A combination of Lotemax (loteprednol etabonate ophthalmic suspension at 0.5%) with the antibiotic Tobramycin is currently under development, aiming to provide a synergistic effect for the treatment of various ocular conditions.
Loteprednol etabonate, introduced in the US as Lotemax and Alrex, demonstrates superior efficacy and an improved safety profile compared to prior ophthalmic steroids due to its metabolic lability and fast enzymatic transformation to inactive metabolites.
References
[1] http://www.webmd.com
[2] https://www.drugbank.ca
[3] http://www.bausch.com
[4] Timothy L. Comstock, Heleen H. DeCory (2012) Advances in Corticosteroid Therapy for Ocular Inflammation: Loteprednol Etabonate, International Journal of Inflammation, 2012, 789623
[5] N. Krug, JM. Hohlfeld, H. Geldmacher, M Larbig, R. Heermann, N. Lavallee, DT. Nguyen, U. Petzold, R. Hermann (2005) Effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an environmental exposure unit, Allergy, 60, 354-359
Originator
Pharmos (US)
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.
Therapeutic Function
Glucocorticoid
Biochem/physiol Actions
Loteprednol Etabonate is an anti-inflammatory corticosteroid (ophthalmology).
Check Digit Verification of cas no
The CAS Registry Mumber 82034-46-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,0,3 and 4 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 82034-46:
(7*8)+(6*2)+(5*0)+(4*3)+(3*4)+(2*4)+(1*6)=106
106 % 10 = 6
So 82034-46-6 is a valid CAS Registry Number.
InChI:InChI=1/C24H31ClO7/c1-4-30-21(29)32-24(20(28)31-13-25)10-8-17-16-6-5-14-11-15(26)7-9-22(14,2)19(16)18(27)12-23(17,24)3/h7,9,11,16-19,27H,4-6,8,10,12-13H2,1-3H3/t16-,17-,18-,19+,22-,23-,24-/m0/s1
82034-46-6Relevant articles and documents
Preparation method of loteprednol etabonate
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, (2020/07/24)
The invention provides a preparation method of loteprednol etabonate. The preparation method comprises the following steps: (1) N-arylation reaction: carrying out a reaction on a compound I with an iodobenzene analogue under an alkaline condition to obtain a compound shown as a formula II; 2) elimination reaction: carrying out a reaction on the compound shown in the formula II with an ethylene oxide analogue in methanol under an alkaline condition to obtain a compound shown in a formula III; 3) esterification reaction: carrying out a reaction on the compound shown in the formula III with ethylchloroformate under an organic alkaline condition to obtain a compound shown in a formula IV; and 4) chlorination reaction: carrying out chlorination reaction on the compound in the formula IV underthe action of potassium persulfate to obtain the loteprednol etabonate. In the reaction route, the cheap and readily available compound I is used as a starting raw material, so that the process conditions are mild, the synthesis steps are simplified, the dosage of toxic reagents is reduced, and the yield is relatively high.
A method for synthesizing loteprednol etabonate and a method for synthesizing intermediate (by machine translation)
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Paragraph 0025; 0031; 0032, (2017/05/05)
The present invention provides a method of synthesizing loteprednol etabonate, comprises the following steps: step 1: to prednisolone as raw material preparation 11 β, 17 α - dihydroxy - 3 - oxo male steroid - 1, 4 - diene - 17 β - carboxylic acid; step 2: adopts the 11 β, 17 α - dihydroxy - 3 - oxo male steroid - 1, 4 - diene - 17 β - carboxylic acid preparation 17 α - ((ethoxy-formyl) oxy) - 11 β - hydroxy - 3 - oxo male steroid - 1, 4 - diene - 17 β - carboxylic acid ethyl carbonic anhydride; step 3: the 17 α - ((ethoxy-formyl) oxy) - 11 β - hydroxy - 3 - oxo male steroid - 1, 4 - diene - 17 β - carboxylic acid ethyl carbonic anhydride adding ethanol into sodium after a period of time by adding chlorine iodine methane then will be chlorine iodine methane. In step 3 can avoid the influence of the introduction of water to the intermediate. (by machine translation)