37927-29-0Relevant articles and documents
Preparation method of loteprednol etabonate intermediate
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Paragraph 0010; 0031; 0036-0037; 0042, (2021/07/14)
The invention provides a preparation method of a loteprednol etabonate intermediate. The preparation method comprises the following steps: carrying out dehydration reaction on 11 alpha-hydroxyl-ADD and a dehydrating agent in an organic solvent to obtain a compound II; carrying out a first addition reaction on the compound II and a halogenating reagent in an organic solvent in the presence of an acid catalyst, and adding a quenching agent to carry out a quenching reaction after the reaction is finished, so as to obtain a compound III; carrying out reduction reaction on the compound III and a metal reducing agent in an organic solvent in the presence of an acid catalyst to obtain a compound IV; carrying out secondary addition reaction on the compound IV and a cyaniding reagent in an organic solvent in the presence of a basic catalyst to obtain a compound V; and carrying out hydrolysis reaction on thecompound V and an acid reagent in an organic solvent to obtain a compound VI, wherein the compound VI is the loteprednol etabonate intermediate. The preparation method saves energy, reduces consumption, and is easy to operate, high in yield and good in purity.
Synthesis method of loteprednol intermediate
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Paragraph 0012; 0066-0071, (2020/05/08)
The invention provides a preparation method of a loteprednol etabonate intermediate, wherein the method comprises that cheap and accessible 11 alpha-hydroxy-ADD as a starting raw material is subjectedto dehydrating, Grignard reaction, hydrolyzing, oxidizing, bromo-hydroxylating and reducing to obtain 17 beta-carboxylic acid (compound VII). The method has the advantages of easily available initialraw materials, high yield, good purity and stable process.
POTENT SOFT ANTI-INFLAMMATORY CORTICOSTEROID COMPOUNDS AND USES THEROF
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Paragraph 0070; 0071, (2019/01/08)
Potent soft corticosteroid pharmaceutical compositions comprising them and method for use as anti-inflammatory agents. Also, a method for softening fluticasone propionate and similar corticosteroids to arrive at potent but safer alternatives. The compound S-fluoromethyl 17α-dichloroacetoxy-6α,9α-difluoro-11β-hydroxy-16a- methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, which is equally potent to but safer than fluticasone, is among those provided. Another compound of particular interest is 2-hydroxyethyl 17α-dichloroacetoxy-6α,9α-difluoro-11β-hydroxy-16β- methyl-3-oxoandrosta-1,4-diene-17β-carboxylate.
A method for synthesizing loteprednol etabonate and a method for synthesizing intermediate (by machine translation)
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Paragraph 0025; 0027; 0028, (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)
Loteprednol preparation method and ophthalmic composition of loteprednol
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Paragraph 0085-0087; 0100-00102; 0115-0117, (2017/09/01)
The present invention relates to a loteprednol preparation method and an ophthalmic composition of loteprednol, particularly to a loteprednol preparation method, which comprises: dissolving a raw material loteprednol in a first organic solvent to obtain a drug-containing solution, adding a second organic solvent to the obtained solution in a dropwise manner under stirring, continuously stirring, filtering, washing the filter cake by using the second organic solvent, and drying the obtained filter cake in a vacuum oven to obtain the product. The invention further provides a loteprednol bulk drug prepared according to the method, an ophthalmic pharmaceutical composition prepared by using the prepared loteprednol as a bulk drug, and uses of the prepared loteprednol in preparation of drugs for treatment or prevention of ocular inflammations or dry eye. The method of the present invention has excellent pharmaceutical properties, wherein the prepared bulk drug and the preparation have excellent stability.
SELECTIVE GLUCOCORTICOID RECEPTOR LIGANDS
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Page/Page column 34; 38, (2015/06/03)
Described herein are certain steroid derivative compounds, for example of formula (I): wherein X1, X2, X3 L, and Ar are as defined herein, pharmaceutical compositions comprising such compounds, the use of such compounds and compositions to specifically target glucocorticoid action, and the use of such compounds and compositions in the treatment of acute and chronic inflammatory conditions, in particular rheumatoid arthritis, haematological and other malignancies, and for causing immunosuppression in the prevention or treatment of transplant rejection, as well as methods of preparing such compounds.
Macrolactonolides: A novel class of anti-inflammatory compounds
Toma?kovi?, Linda,Komac, Marijana,Makaruha Stegi?, Oresta,Muni?, Vesna,Rali?, Jovica,Stani?, Barbara,Banjanac, Mihailo,Markovi?, Stribor,Hrva?i?, Bo?ka,?ip?i? Paljetak, Hana,Padovan, Jasna,Glojnari?, Ines,Erakovi? Haber, Vesna,Mesi?, Milan,Mer?ep, Mladen
, p. 321 - 332 (2013/02/23)
A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.
Etiprednol dicloacetate, a new soft glucocorticoid drug candidate. Development of chemistry
Csanadi,Horvath,Szekeres,Hasko,Ila,Ivanics,Patthy,Salat,Seres,Pallagi,Toth,Szederkenyi,Konya,Tegdes,Bodor,Zubovics, Zoltan
, p. 349 - 359 (2007/10/03)
During development of chemistry of the soft drug candidate etiprednol dicloacetate (BNP-166) 1) optimization studies on the three-step chemical synthesis resulted in a process that could be scaled-up to the kg level, 2) the impurity profile was determined, 3) synthetic routes were developed for the preparation of the radiolabeled target compound, and 4) a series of hydroxylated metabolites was prepared.
Effect of cyclodextrins on the solubility and stability of a novel soft corticosteroid, loteprednol etabonate
Bodor, Nicholas,Drustrup,Wu
, p. 206 - 209 (2007/10/03)
To increase the aqueous solubility and stability of the soft corticosteroid loteprednol etabonate (LE), drug complexation using various cyclodextrins (CDs), such as γ-cyclodextrin (γ-CD), 2-hydroxypropyl-β- cyclodextrin (HPBCD), maltosyl-β-cyclodextrin (MBCD), mixture of glucosyl/maltosyl-α-, β-, and γ-cyclodextrin (GMCD), and heptakis (2,6-di- O-methyl)-β-cyclodextrin (DMCD), were attempted. The solubilizing and stabilizing effects of CD by itself or combined with various co-solvents were also investigated. Micronized (5 micron) LE was mixed in various aqueous CD or CD with cosolvent solutions. After equilibration and filtration at 23 °C, the solubility of LE was determined by HPLC. Subsequently, the stability of LE in the solutions was also determined by following the LE concentration change in the solution for an appropriate period. CD complexation significantly increased the aqueous solubility and stability of LE. The increase in solubility displayed a concentration dependency on CDs (0-50%). Among the five CDs used, DMCD showed the highest effects on the solubility (4.2-18.3 mg/ml in 10-50% DMCD) and stability (t90 > 4 years at 4 °C, when LE 0.5 mg/ml was dissolved in 10% DMCD solution) of LE. By adding co- solvents, such as glycerol, propylene glycol (PG), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP-10), the solubility of LE in DMCD solutions was further increased. Degradation of LE to the corresponding metabolites, Δ1- cortienic acid etabonate (AE) and Δ1-cortienic acid (A), in aqueous CD solutions appeared to be a predicted, two-step kinetics. Differential Scanning Calorimetry (DSC) was used to assist explaining the solubilizing and stabilizing activity differences between CDs. LE/CD mixture or lyophilized LE/CD complex was scanned at a rate of 20 °C/min. The exothermic peak found in the DSC diagram with LE/DMCD sample, but not with LE/HPBCD samples, suggests a stronger complex formed between LE and DMCD, resulting in higher solubility and stability of LE in DMCD than in HPBCD.
