82034-46-6 Usage
Description
Different sources of media describe the Description of 82034-46-6 differently. You can refer to the following data:
1. Loteprednol (as Loteprednol Etabonate) is a topical anti-inflammatory corticosteroid. Loteprednol etabonate (LE) has a 17α-chloromethyl ester, in lieu of a ketone group, and a 17β-etabonate group. LE is highly lipophilic and binds with high affinity to the glucocorticoid receptor. Any unbound LE is metabolized to inactive metabolites.
Loteprednol etabonate is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitis. It is used in ophthalmic ointment for the treatment of post-operative inflammation and pain following ocular surgery. As a nasal spray, it is used for the treatment and management of seasonal allergic rhinitis.
2. 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.
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
Chemical Properties
x
Originator
Pharmos (US)
Uses
Different sources of media describe the Uses of 82034-46-6 differently. You can refer to the following data:
1. An ophthalmic corticosteroid. Used as an anti-inflammatory
2. 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
3. An ophthalmic corticosteroid. Used as an anti-inflammatory.
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.
Brand name
Alrex (Bausch & Lomb); Lotemax
(Bausch & Lomb); Lotemax (Pharmos);Lotemax (0.5%）.
Therapeutic Function
Glucocorticoid
General Description
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).
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)
