1141397-80-9

Cedazuridine (E7727) (Compound 7a) is an orally active cytidine deaminase (CDA) inhibitor with an IC50 value of 0.4 μM. Cedazuridine can be used for cancer research[1].

Cedazuridine increases the half-life of decitabine by inhibiting cytosine deaminase, thereby improving the efficacy of combination therapy and having a better therapeutic effect than decitabine alone.

The synthesis began with the readily available protected gemcitabine precursor 244. The 6-aminopyridine was converted to the corresponding dihydrouracil 245 in 97% yield via acid-mediated transfer hydrogenation. Reduction under Luche conditions followed by treatment with methanolic ammonia reduced the amide carbonyl group and removed the two phenoxyester protecting groups to afford dihydrouracil 246 as a mixture of two diastereoisomers. Treatment of 246 with a catalytic amount of DBU in aqueous acetonitrile afforded a diastereomeric mixture in which cedaruridine and its cyclic amino alcohol 247 were present in a 9:1 ratio. Reconstitution of the undesired diastereomer 247 in a cold acetonitrile/water mixture (5:1) afforded cedaruridine in 86% yield.

4°C, protect from light

[1] Ferraris D, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem. 2014 Mar 27; 57(6):2582-8. DOI:10.1021/jm401856k
[2] Ramsey H E, et al. Oral azacitidine and cedazuridine approximate parenteral azacitidine efficacy in murine model. Targeted Oncology, 2020, 15(2): 231-240.