1334318-82-9

Upstream product

• 1360816-01-8 1-(2-aminoethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea 
• 471-53-4 enoxolone 
• 912541-99-2 N-(2-aminoethyl)-3β-hydroxy-11-oxo-olean-12-en-30-amide 
• 16588-74-2 3,5-ditrifluoromethylisocyanate 
• 1334318-59-0 N-[2-(tert-butoxycarbonylamino)ethyl]glycyrrhetinamide 

Relevant academic research and scientific papers

Synthesis and plasma pharmacokinetics in CD-1 mice of a 18β-glycyrrhetinic acid derivative displaying anti-cancer activity

Objectives The plasma pharmacokinetic profile in CD-1 mice of a novel 18β-glycyrrhetinic acid (GA) derivative, which displays in vitro anti-cancer activity, was assessed. Methods This study involved an original one-step synthesis of N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)- glycyrrhetinamide, (2) a compound that displays marked anti-proteasome and anti-kinase activity. The bioselectivity profile of 2 on human normal NHDF fibroblasts vs human U373 glioblastoma cells was assessed. Maximal tolerated dose (MTD) profiling of 2 was carried out in CD1 mice, and its serum pharmacokinetics were profiled using an acute intravenous administration of 40 mg/kg body weight. Key findings Compound 2 displayed IC50 in vitro growth inhibitory concentrations of 29 and 8 μm on NHDF fibroblasts and U373 glioblastoma cells, respectively, thus a bioselectivity index of ～4. The intravenous pharmacokinetic parameters revealed that 2 was rapidly distributed (t1/2dist of ～3 min) but slowly eliminated (t1/2elim = ～77 min). Conclusions This study describes an original and reliable nanoemulsion of a GA derivative with both anti-proteasome and anti-kinase properties and that should be further tested in vivo using various human xenograft or murine syngeneic tumour models with both single and chronic intravenous administration.

Utilization of [11C]phosgene for radiosynthesis of N-(2-{3-[3,5-bis(trifluoromethyl)]phenyl[11C]ureido}ethyl) glycyrrhetinamide, an inhibitory agent for proteasome and kinase in tumors

N-(2-{3-[3,5-Bis(trifluoromethyl)]phenylureido}ethyl)glycyrrhetinamide (2), an ureido-substituted derivative of glycyrrhetinic acid (1), has been reported to display potent inhibitory activity for proteasome and kinase, which are overexpressed in tumors. In this study, we labeled this unsymmetrical urea 2 using [11C]phosgene ([11C]COCl2) as a labeling agent with the expectation that [11C]2 could become a positron emission tomography ligand for the imaging of proteasome and kinase in tumors. The strategy for the radiosynthesis of [11C]2 was to react hydrochloride of 3,5-bis(trifluoromethyl)aniline (4·HCl) with [ 11C]COCl2 to possibly give isocyanate [11C]6, followed by the reaction of [11C]6 with N-(2-aminoethyl) glycyrrhetinamide (3).

18-BETA-GLYCYRRHETINIC ACID DERIVATIVES WITH ANTI-TUMOR ACTIVITY

The invention relates to the medical and cosmetic field, more precisely the field of anticancer treatment and treatment of inflammatory diseases and diabetes and the field of anti-aging or anti-wrinkling agents using newly synthesized 18β-glycyrrhetinic acid derivatives and there use in the treatment of said disorders or symptoms.

N -(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b): A novel anticancer glycyrrhetinic acid derivative that targets the proteasome and displays anti-kinase activity

18-β-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in cancer cells. The current study aims to characterize the anticancer effects of 17 novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be the most potent compound, with IC50in vitro growth inhibitory concentrations in single-digit micromolarity in a panel of 8 cancer cell lines. Compound 6b is cytostatic and displays similar efficiency in apoptosis-sensitive versus apoptosis-resistant cancer cell lines through, at least partly, the inhibition of the activity of a cluster of a dozen kinases that are implicated in cancer cell proliferation and in the control of the actin cytoskeleton organization. Compound 6b also inhibits the activity of the 3 proteolytic units of the proteasome. Compound 6b thus represents an interesting hit from which future compounds could be derived to improve chemotherapeutic regimens that aim to combat cancers associated with poor prognoses.