4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• , we report the synthesis of 4-(1-methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones via a reversible transimination reaction between Schiff’ base (C=N) linkage-containing pyrrolidine-2,3-dione derivatives and methylamine with yields of 80 to 92%. In addition to nuclear magnetic resonance

• derivatives; iNOS; pyrrolidine-2,3-dione derivatives; pyrrolidine-2,3-diones; pyrrolidine-2,3-diones targeting reversible transimination reaction; Introduction Nitric oxide (NO) is an important signaling molecule in numerous physiological processes such as neuronal tranmission, immue response, inflammatory

• pyrrolidine-2,3-dione derivatives could inhibit biomacromolecules (DNA, BSA, mPGES-1 or CDKs) and consequently, enable them to be candidates for Alzheimer's disease [11], anti-inflammatory [12][13][14][15][16][17], and antitumor drug discovery [12]. Furthermore, pyrrolidine-2,3-diones are also important

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was

• between the amino proton and the carbon of the methyl group separated by three σ-bonds. Thus, the reaction between 2-pyrrolidinone derivatives 4a–c and nucleophilic amines 9a–d is confirmed to occur at the carbonyl group of the acetyl moiety to achieve 1,4,5-trisubstituted pyrrolidine-2,3-dione

• derivatives present in the enamine form and stabilized by intramolecular hydrogen bonds (Table 5). Single-crystal X-ray diffraction confirmed the structure of 10aa (Figure 3) as well as the presence of the intramolecular N15–H15···O13 hydrogen bond [N15–H15: 0.92(3) Å, H15···O13: 1.90(3) Å, N15···O13: 2.699(3