Han, Xinya published the artcileBiological evaluation and SAR analysis of novel covalent inhibitors against fructose-1,6-bisphosphatase, Formula: C9H6N2O2, the publication is Bioorganic & Medicinal Chemistry (2020), 28(18), 115624, database is CAplus and MEDLINE.
Herein, a series of nitrostyrene derivatives I (R1 = H, F, Me, etc.; R2 = H, Cl, Me, etc.; R3 = H, Cl, Br, Me) were synthesized, and their inhibitory activities against Fructose-1,6-bisphosphatase (FBPase) were investigated in vitro. Most of the prepared compounds exhibit potent FBPase inhibition (IC50 < 10μM). Specifically, when the substituents of F, Cl, OMe, CF3, OH, CO2H, or 2-nitrovinyl were installed at the R2 (meta-) position of the benzene ring, the FBPase inhibitory activities of the resulting compounds increased 4.5-55 folds compared to those compounds with the same groups at the R1 (para-) position. In addition, the preferred substituents at the R3 position were Cl or Br, thus compound I (R1 = NO2; R2 = H; R3 = Cl) exhibited the most potent inhibitory activity (IC50 = 0.15μM). The mol. docking and site-directed mutation suggest that C128 and N125 are essential for the binding of I (R1 = NO2; R2 = H; R3 = Cl) and FBPase, which is consistent with the C128-N125-S123 allosteric inhibition mechanism. The reaction enthalpy calculations show that the order of the reactions of compounds with thiol groups at the R3 position is Cl > H > CH3. CoMSIA anal. is consistent with proposed binding mode. The effect of compounds I (R1 = 1,2,4-triazol-1-yl; R2 = H; R3 = H) and I (R1 = NO2; R2 = H; R3 = Cl) on glucose production in primary mouse hepatocytes were further evaluated, showing that the inhibition was 71% and 41% at 100μM, resp.
Bioorganic & Medicinal Chemistry published new progress about 5153-73-1. 5153-73-1 belongs to nitriles-buliding-blocks, auxiliary class Nitrile,Alkenyl,Nitro Compound,Benzene, name is (E)-4-(2-Nitrovinyl)benzonitrile, and the molecular formula is C9H6N2O2, Formula: C9H6N2O2.
Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts