10379-73-4

Upstream product

• 471-53-4 enoxolone 
• 108-24-7 acetic anhydride 
• 53402-18-9 3β-acetoxy-11-dioxyglycyrrhetic acid 
• 75-36-5 acetyl chloride 
• 64-19-7 acetic acid 
• 1405-86-3 glycyrrhizin 

Downstream Products

• 471-53-4 enoxolone 
• 182682-55-9 (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-Hydroxy-2-[5-mercapto-4-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-2,4a,6a,6b,9,9,12a-heptamethyl-1,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,14b-octadecahydro-2H-picen-13-one 
• 182682-74-2 C₄₀H₅₇N₃O₅S 
• 1477-44-7 methyl glycyrrhetinate 
• 51298-47-6 N-(L-phenylalanine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-amide 
• 1620133-40-5 N-(L-phenylalanine tert-butyl ester)-3β-acetyl-11-oxo-olean-12-en-18β-H-30-amide 

Relevant academic research and scientific papers

Novel unsaturated glycyrrhetic acids derivatives: Design, synthesis and anti-inflammatory activity

To develop novel anti-inflammatory agents, a series of unsaturated glycyrrhetic acids were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. The structure-activity relationship (SAR) of NO inhibitory activity was analyzed. α,β-Unsaturated glycyrrhetic acids showed better activity, among them, compounds 6k and 6l with piperazine unit exhibited the most potent nitric oxide (NO) and interleukin-6 (IL-6) inhibitory activity (IC50 = 13.3 and 15.5 μM respectively). Furthermore, compound 6k could also significantly suppress LPS-induced iNOS and COX-2 expression and IL-6 production through MAPKs and NF-kB signaling pathway.

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.

Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability

Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80 μM and 3.52 μM, respectively. The enzyme inhibition ratio of nine compounds at 10 μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.

Synthesis and Anti-Microbial Activity of Benzylidenhydrazides of Glycyrrethic Acid

Abstract: New derivatives of glycyrrhetic acid with hydrazide pharmacophore groups were synthesized and their antimicrobial activity was evaluated. Hydrazide of 3-O-acetyl-N'-(4-hydroxybenzylidene) glycyrrhetic acid exhibited the highest antimicrobial activity. This compound had both an antibacterial effect against Escherichia coli, Proteus vulgaris, Klebsiella pneumonia, Staphylococcus aureus, Citrobacter diversus, Enterobacter aerogenes, Pseudomonas aeruginosa, and Enterobacter cloacae and antifungal activity against the Candida albicans fungus. The minimum inhibitory concentrations of this compound and pimafucin were similar for Candida albicans.

Long circulating anionic liposomes for hepatic targeted delivery of cisplatin

In this paper, a receptor-mediated liposomal drug delivery system (DDS) was developed aiming to deliver cisplatin (cis-diaminedichloroplatinum(ii); CDDP) targeting the liver. Acetyl glycyrrhetinic acid (AGA) was chosen as the hepatic targeting ligand and acetyl glycyrrhetinic acid-poly(ethylene glycol)-stearate (AGA-PEG-ST) was synthesized. Anionic 5-cholestene-3-beta-ol-3-hemisuccinate (CHO-HS) was also synthesized. The liposomal CDDPs were prepared by employing these functional moieties with phosphatidylcholine (PC) at various ratios. Meanwhile, methoxypolyethylene glycol-stearate (MPEG-ST) with an analogous structure but without AGA was also prepared as a control. The particle sizes of AGA modified liposomes ranged from 120 nm to 180 nm and the zeta potentials were located between -39.7 mV and -3.18 mV. The liposomes had encapsulation percentages of 51.5-61.7% and a loading capacity of 23.2-26.7% for CDDP. The transmission electron microscopy (TEM) observations showed that the liposomes had spherical morphologies with homogeneous distribution. In vitro cytotoxicity of CDDP-loaded liposomes against HepG2 human liver cancer cells and A549 human lung epithelial carcinoma cells were evaluated by MTT assays. The results demonstrated that the introduction of AGA could enhance the cytotoxicity of liposomal CDDP against HepG2 cells but showed less significant impact on A549 cells. CLSM observation and FCM measurement further confirmed that AGA modified liposomes had a stronger affinity to HepG2 cells than that of liposomes without AGA. The tissue distribution of calcein in mice indicated that AGA modified liposomes resulted in higher accumulation in the liver than that of liposomes without the AGA ligand. These results demonstrated the promise of AGA decorated anionic liposomes for hepatic targeted delivery of cisplatin.

Fluorofunctionalization of C=C Bonds with Selectfluor: Synthesis of β-Fluoropiperazines through a Substrate-Guided Reactivity Switch

The halofunctionalization of alkene substrates remains an essential tool for synthetic chemists. Herein, we report regioselective ammoniofluorination of unactivated alkenes through photochemical means. A one-pot transformation of the ammonium fluoride products into pharmaceutically relevant β-fluoropiperazines is highlighted. Furthermore, a substrate-guided reactivity switch is observed: certain alkenes are shown to react with the same fluorinating reagent to instead give the less-substituted fluoride. We hope that the ammoniofluorination reaction will be of utility in the area of medicinal chemistry, where nitrogen and fluorine are among the most important heteroatoms.

A Simple Aliphatic Diamine Auxiliary for Palladium-Catalyzed Arylation of Unactivated β-C(sp3)-H Bonds

Palladium-catalyzed β-C(sp3)-H arylation of aliphatic acid derivatives was achieved by means of 2-dimethylaminoethylamine auxiliary as a directing group. The β-C(sp3)-H arylation reactions with aryl and heteroaryl iodides efficiently afforded the corresponding arylated hydrocinnamic acid derivatives. Direct β-C(sp3)-H alkynylation, and arene C?H arylation and alkynylation were also realized under the same or slightly modified conditions. The aliphatic diamine auxiliary in the products could be readily removed by methanol in the presence of BF3 ? OEt2. In comparison with the widely used bidentate nitrogen-containing directing groups, 2-dimethylaminoethylamine is a simple, cheap, readily available and removable, and atom-economical directing group for C?H functionalization. (Figure presented.).

Synthesis and self-assembly properties of a glycyrrhetinic acid conjugate containing uracil and 2,6-diaminopyridine units

A novel glycyrrhetinic acid conjugate containing uracil and 2,6-diaminopyridine units was synthesized and the exclusive supramolecular dimeric structure through six intermolecular hydrogen bonds was characterized by NMR spectroscopy and ESI-MS. The supramolecular dimeric structure could recognize the polar molecule in aprotic polar solvents.

Synthesis and biological evaluation of novel hydrogen sulfide releasing glycyrrhetic acid derivatives

A series of hybrids, which are composed of glycyrrhetic acid (GA) and slowly hydrogen sulfide-releasing donor ADT-OH, were designed and synthesized to develop anticancer and anti-inflammatory agents. Most of the compounds, whose inhibitory rates were comparable to or higher than those of GA and aspirin, respectively, significantly inhibited xylene-induced ear edema in mice. Especially, compound V 4 exhibited the most potent inhibitory rate of 60.7%. Furthermore, preliminary structure–activity relationship studies demonstrated that 3-substituted GA derivatives had stronger anti-inflammatory activities than the corresponding 3-unsubstituted GA derivatives. In addition, anti-proliferative activities of compounds V1?9 were evaluated in three different human cancer cell lines. Compound V4 showed the most high potency against all three tumor cell lines with IC50 values ranging from 10.01 μM in Hep G2 cells to 17.8 μM in MDA-MB-231 cells, which were superior to positive GA.

Synthesis and biological evaluation of novel curcuminoid derivatives

Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 μ M /mL against selected medically important Gram-positive cocci (S aureus and S viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 μ M.