5697-56-3

Usage

Originator

Biogastrone,Winthrop,UK,1963

Uses

Glucocorticoid.

Manufacturing Process

23.5 g of glycyrrhetinic acid were dissolved in 50 cc of dry pyridine. A solution of 6.0 g of succinic anhydride in 30 cc of dry pyridine was added, followed by 30 cc of dry triethylamine and then, for washing purposes, 5 cc of dry pyridine. The solution was heated on a boiling water bath for ten hours and then poured into excess of dilute hydrochloric acid and ice. The fine gray precipitate formed was filtered off, washed with water, dissolved in chloroform, and the solution repeatedly extracted with dilute hydrochloric acid and later with water. It was dried over sodium sulfate and evaporated to dryness. Crystallization from methanol, using charcoal to effect decolorization, gave the hydrogen succinate as cream-colored crystals, MP 291° to 294°C, with previous softening.One molecular proportion of glycyrrhetinic acid hydrogen succinate was ground with a dilute (5%) aqueous solution containing two molecular proportions of sodium hydroxide. The solution was filtered and evaporated in vacuum over concentrated sulfuric acid. The sodium salt is then obtained as a creamy white water-soluble solid. Glycyrrhetinic acid is obtainable from licorice root.

Therapeutic Function

Antiinflammatory (gastric)

Safety Profile

Poison by intravenous andintraperitoneal routes. Moderately toxic by ingestion andsubcutaneous routes. Human systemic effects byingestion: muscle weakness and flaccid paralysis. Whenheated to decomposition it emits acrid smoke and fumes.

InChI:InChI=1/C34H50O7.2Na/c1-29(2)23-10-13-34(7)27(32(23,5)12-11-24(29)41-26(38)9-8-25(36)37)22(35)18-20-21-19-31(4,28(39)40)15-14-30(21,3)16-17-33(20,34)6;;/h18,21,23-24,27H,8-17,19H2,1-7H3,(H,36,37)(H,39,40);;/q;2*+1/p-2/t21-,23?,24-,27?,30+,31-,32-,33+,34+;;/m0../s1

Upstream product

• 471-53-4 enoxolone 
• 45160-42-7 succinic anhydride 
• 108-30-5 succinic acid anhydride 

Relevant academic research and scientific papers

Glycyrrhetinic acid derivative ASBT as well as preparation method and application thereof

The invention discloses a glycyrrhetinic acid derivative ASBT as well as a preparation method and application thereof, and the glycyrrhetinic acid derivative ASBT disclosed by the invention has a structure shown as a general formula I. The preparation method has the beneficial effects that the synthesis is simple, the reaction conditions are mild, and the like.

Glycyrrhetinic acid derivative LGT as well as preparation method and application thereof

The invention discloses a glycyrrhetinic acid derivative LGT as well as a preparation method and application thereof, and the glycyrrhetinic acid derivative LGT has a structure as shown in a general formula I. The glycyrrhetinic acid derivative LGT has the characteristics of simple synthesis method, mild reaction conditions and the like.

Glycyrrhetinic acid derivative BGU as well as preparation method and application thereof

The invention discloses a glycyrrhetinic acid derivative BGU as well as a preparation method and application thereof, and the glycyrrhetinic acid derivative BGU has a structure as shown in a general formula I. The preparation method has the beneficial effects that the synthesis is simple, the reaction conditions are mild, and the like.

Enhanced delivery of doxorubicin to the liver through self-assembled nanoparticles formed via conjugation of glycyrrhetinic acid to the hydroxyl group of hyaluronic acid

Liver-targeted nanoparticles is highly desired for better therapy of liver cancer. In this study, enhanced delivery of doxorubicin (DOX) to the liver cells through self-assembled nanoparticles formed via conjugation of glycyrrhetinic acid (GA) to the hydroxyl group of hyaluronic acid (HA) was investigated. The DOX loaded hyaluronic acid-glycyrrhetinic acid succinate (HSG) conjugates based nanoparticles (HSG/DOX nanoparticles) were sub-spherical in shape with particle size in the range of 180–280 nm, the drug loading was drug-to-carrier ratio and GA graft ratio dependent. In vitro release study suggested that the release of DOX from HSG nanoparticles was sustained and the release rate was pH and GA graft ratio dependent. MTT assay indicated the HSG/DOX nanoparticles presented a GA-dependent cytotoxicity to HepG2 cells. Pharmacokinetics study demonstrated the HSG/DOX nanoparticles could prolong blood circulation time of DOX and had a higher AUC value than that of DOX solution. Furthermore, tissue distribution study revealed the HSG/DOX nanoparticles significantly increased the accumulation of DOX in the liver and meanwhile decreased the cardiotoxicity and nephrotoxicity of DOX. Moreover, the liver targeting enhancing capacity was HSG conjugate structure dependent. The accumulation of HSG-20/DOX, HSG-12/DOX, and HSG-6/DOX nanoparticles in the liver was 4.0-, 3.1-, and 2.6-fold higher than that of DOX solution. In vivo imaging analysis further demonstrated HSG nanoparticles not only had better liver targeting effect, but also presented superior tumor targeting efficiency, and the tumor targeting capacity was also GA-dependent. These results indicated that HSG conjugates prepared via modifying the hydroxyl groups of HA have promising potential as a liver-targeting nanocarrier for the delivery of hydrophobic anti-tumor drugs.

Glycyrrhetinic acid-modified PEG-PCL copolymeric micelles for the delivery of curcumin

In this study, glycyrrhetinic acid (GA) was conjugated with mono amino poly (ethylene glycol)-b-poly (ε-caprolactone) (H2N-PEG-PCL) with succinate linker to obtain the GA-modified PEG-PCL (GA-PEG-PCL). By way of thin film hydration method, curcumin was encapsulated into GA-PEG-PCL copolymer to form stable micelles with 93.76% of encapsulation efficiency and 11.93% of drug loading capacity. The micelles enhanced curcumin's water-solubility to 1.87 mg/ml, being 1.70 × 105 times higher than free curcumin. X-ray diffraction and FT-IR analysis confirmed the encapsulation of CUR into copolymeic micelles with an amorphous state. Hemolysis datum of blank micelles showed its biocompatibility. Compared with GA-unconjugated micelles, curcumin-loaded GA-PEG-PCL micelles showed slower in vitro release of drug, but they displayed better in vitro cytotoxicity against HepG2 at about 40 μM because of its selective accumulation in HepG2 cells induced by GA. The results showed that GA-PEG-PCL copolymer could be a promising drug carrier for liver targeted drug delivery.

Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid

Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6–260.7?nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.

Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic saponin, through a molecular simplification of the carbohydrate moiety

Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural products found in the Liquorice (Glycyrrhiza glabra L.) root extract. This saponin is known for its in vitro and in vivo thrombin inhibitory activity. The design and synthesis of five glycyrrhizin derivatives were carried out to improve the natural product activity. Compound 3b, a phthalic ester derivative of glycyrrhizin, presented a more pronounced thrombin inhibition (IC 50 = 114.4 ± 1.3 μm) than the saponin (IC50 = 235.7 ± 1.4 μm). Molecular docking simulations performed to investigate the molecular interaction between compound 3b and the enzyme indicate that this product is, as previously determined for glycyrrhizin, an allosteric thrombin inhibitor. We report in this article the semisynthesis and the in vitro thrombin inhibitory activity of the glycyrrhetinic acid hemiphthalic ester 3b. This activity was found to be more pronounced than of the saponin glycyrrhizin.

Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases

The effect of glycyrrhetinic acid (GA) and GA-derivatives towards 11β-hydroxysteroid dehydrogenase (11β-HSD) was investigated. Novel compounds with modifications at positions C-3, C-11 and C-29 of the GA skeleton were prepared. Single crystal X-ray diffraction data of selected substances are reported and discussed.

Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives

This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3 μM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC50 of 0.22 μM, which was approximately 100-fold more potent than glycyrrhetinic acid.