abstract |
Seven-membered heterocyclic nucleosides used to inhibit the deamination enzyme responsible for the inactivation of arabinosylcytosine (ara-C). Preferred nucleosides containing a seven-member aglycone are as follows:R = H, benzoyl, para-nitrobenzoylX = H, ORA = R, mono-, di- and tri-phosphates (P0<sub>3</sub>E<sub>2</sub>, P<sub>2</sub>0<sub>6</sub>E<sub>3</sub>, P<sub>3</sub>O<sub>9</sub>E<sub>4</sub>)E =H, NaPreferred aglyconies are as follows:1a: X = OCH<sub>2</sub>CH<sub>2</sub>01b: X = SCH<sub>2</sub>CH<sub>2</sub>S1c: X = O1d: X = H, OH1e: X = 2HActive components utilized against pyrimidine deaminases from mammalian tissues (mouse kidney and human liver) showed optimum advantage when compared with tetrahydrouridine (THU). |