Liu, Bin; Hu, Longqin published the artcile< 5'-(2-Nitrophenylalkanoyl)-2'-deoxy-5-fluorouridines as potential prodrugs of FUDR for reductive activation>, COA of Formula: C9H9NO4, the main research area is FUDR nitro containing prodrug preparation reduction cyclization; aminophenylalkanoate ester FUDR prodrug preparation reduction cyclization.
Four 5′-(2-nitrophenylalkanoyl)-2′-deoxy-5-fluorouridines (1a-d) were designed and synthesized as potential prodrugs of FUDR for reductive activation. Two Me groups were introduced α to the ester carbonyl to increase both the rate of cyclization activation and the stability of the conjugates towards serum esterases. Chem. reduction of the nitro group into an amino leads to cyclization and release of the active FUDR. Kinetic anal. of the cyclization activation process indicates that the two Me groups α to the ester carbonyl restrict the rotational freedom of ground state mol. and promote the cyclization reaction. However, the two Me groups also were found to render the conjugates as poor substrates of E. coli B nitroreductase. Conjugate 1c, without the two Me groups, was reduced by E. coli B nitroreductase (t1/2 = 8 h) to give two products, a N-hydroxyl lactam and the drug FUDR, suggesting that the enzymic reduction and subsequent cyclization activation proceeded through the hydroxylamine intermediate. These results indicate that cyclization activation will occur once the nitro group is reduced either to an amino or to a hydroxylamino group. The fact that the amino intermediates cyclized easily to release the incorporated drug FUDR suggests the feasibility of using peptide-linked acyl 2-aminophenylalkanoic acid esters as potential prodrugs for proteolytic activation.
Bioorganic & Medicinal Chemistry published new progress about Blood serum (prodrugs stability in human blood serum). 30095-98-8 belongs to class esters-buliding-blocks, and the molecular formula is C9H9NO4, COA of Formula: C9H9NO4.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics