Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety and structurally similar ester derivatives were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound 3j exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound 3j exerted a moderate inhibiting effect on the ALK. The results of molecular docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biological data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures 4d, 4g, 4h, 4j, and 4n were studied by X-ray crystallographic analyses.

In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.

C₉H₇ClN₂OS, monoclinic, P2₁/n (no. 14), a = 8.3507(3) Å, b = 12.3768(4) Å, c = 10.2340(4) Å, β = 96.857(4)°, V = 1050.17(7) ų, Z = 4, R_gt (F) = 0.0673, wR_ref (F ²) = 0.2013, T = 296(2) K.

Ethyl 2-ethylimidazo[1,2-a]pyridine-3-carboxylate is an important intermediate for the synthesis of imidazo[1,2-a]pyridine compounds with imidazo ring. In this article, the title compound is obtained by a three-step reaction. The molecular structure is further calculated using density functional theory (DFT), which was compared with the x-ray diffraction value. The results of the conformational analysis indicate that the molecular structure optimized by DFT is consistent with the crystal structure determined by single crystal x-ray diffraction. In addition, the molecular electrostatic potential and frontier molecular orbitals of the title compound are further investigated by DFT, and some physicochemical properties of the compound are revealed.