2-Hydroxy-N-(4-hydroxyphenyl)-benzamide

Uses

Osalmid is a ribonucleotide reductase small subunit M2 (RRM2) targeting compound; suppresses ribonucleotide reductase activity with an IC50 of 8.23 μM.

Definition

ChEBI: Osalmid is an organic molecular entity.

Biochem/physiol Actions

Osalmid is a potent inhibitor of ribonucleotide reductase small subunit M2 (RRM2) that potently inhibits HBV DNA and cccDNA synthesis in HepG2.2.15 cells. Osalmid inhibits RR (ribonucleotide reductase) activity in vivo, and exhibits synergistic effect with lamivudine on inactivation mutant HBV strain. Osalmid is a biliation activator (choleretic agent), but a mechanism of this activity remains unknown.

Synthesis

To the reaction vessel, 0.07 mol 4-aminophenol, 0.076 mol salicylamide and 80 mL ethyl acetate were added and the stirring speed was controlled to be 150 rpm. 0.031 mol stannous chloride was added slowly and a gradual darkening of the color of the solution was observed. After the addition was completed, the temperature was slowly raised to 170 °C and the reaction was maintained for 6 h. The reaction was carried out at 2.1 °C. After completion of the reaction, vacuum distillation was carried out at 2.1 kPa to remove some of the ethyl acetate. The solution was cooled to 38 °C and subsequently the reaction mixture was poured into 500 mL of sodium bisulfite solution with a mass fraction of 23%. The pH was adjusted to 4 with 33% oxalic acid solution to induce precipitation of the solid. The solid product was separated by filtration and purified by recrystallization with 87% ethylenediamine solution to give 13.47 g of white solid 2-hydroxy-N-(4-hydroxyphenyl)benzamide in 84% yield.

in vivo

References

[1] Liu X, et al. Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein. Biochem Pharmacol. 2016 Mar 1;103:118-28. DOI:10.1016/j.bcp.2016.01.003