Novel α-glucosidase inhibitors with a tetrachlorophthalimide skeleton

Thalidomide as a Multi‐Template for Development of Biologically Active Compounds

“…6) indicated that CP0P 2 inhibits the enzyme non-competitively (the inhibition curve crosses the horizontal axis), while CP4P 3 inhibits it competitively (the inhibition curve crosses the vertical axis), as dNM does. The results suggest that CP4P 3 (and possibly other methylene-spacered tetrachlorophthalimide derivatives 11 -15) inhibits a-glucosidase by binding to its catalytic site in a mutually competitive manner with the cognate substrate, which implies that the methylene-spacered tetrachlorophthalimide group could be a sugar mimic [16].…”

“…Some derivatives of dNM have been shown to be effective against AIDS and B-and C-type viral hepatitis. Our structural development studies based on a-glucosidase-inhibiting activity yielded tetrachlorophthalimide derivatives (Table 2) [16]. As shown in Table 2, all of the tetrachlorophthalimide derivatives (2, 3, 11 -15) showed more potent a-glucosidase-inhibiting activity (IC 50 of 2.0 -10.9 lM) than dNM (IC 50 = 47.6 lM).…”

“…As mentioned above, we have developed a series of potent a-glucosidase inhibitors, including CP0P 2 and CP4P 3 (Fig. 2, Table 2) [16]. CP0P 2 is a non-competitive inhibitor of a-glucosidase, whereas CP4P 3 is a competitive inhibitor.…”

Synthesis of N-substituted-3,4,5,6-tetrachlorophthalimide using trichloroacetimidate C-C bond formation method

“…1,2 Considerable attention was directed to the design and synthesis of α-glucosidase inhibitors. Phthalimides, 3 tetrachlorophthalimides, and N-substituted phthalimides [4][5][6] are well known α-glucosidase inhibitors. Inhibition of this enzyme retard the uptake of dietary carbohydrates to absorbable monosaccharides, 4 and due to that tetrachlorophthalimides can be potentially valuable for various diseases treatment as antiviral, 5 diabetes, certain forms of hyperlipoteinemia, and obesity.…”

“…Inhibition of this enzyme retard the uptake of dietary carbohydrates to absorbable monosaccharides, 4 and due to that tetrachlorophthalimides can be potentially valuable for various diseases treatment as antiviral, 5 diabetes, certain forms of hyperlipoteinemia, and obesity. 6,7 Structural development studies showed that the hydrophobic groups at the N atom are of crucial effect. 8 Thus, N-Phenyl- 3,4,5,6-tetrachlorophthalimide (I) and N-(4-phenylbutyl)-3,4,5,6-tetrachloro-phthalimide (II) showed very potent α-Glucosidase inhibitory activity, being more potent than 1-deoxynojirimycin.…”