Seven-membered ring compounds as inhibitors of cytidine deaminase.

摘要

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:
<Chemistry id="chema01" num="0001"><Image id="ia01" he="41" wi="88" file="IMGA0001.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry><UnorderedLists id="ula01" listStyle="none"><ListItem>R = H, benzoyl, para-nitrobenzoyl</ListItem><ListItem>X = H, OR</ListItem><ListItem>A = 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>)</ListItem><ListItem>E =H, Na</ListItem></UnorderedLists>

Preferred aglyconies are as follows:
<Chemistry id="chema02" num="0002"><Image id="ia02" he="28" wi="80" file="IMGA0002.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry><UnorderedLists id="ula02" listStyle="none"><ListItem>1a: X = OCH<Sub>2</Sub>CH<Sub>2</Sub>0</ListItem><ListItem>1b: X = SCH<Sub>2</Sub>CH<Sub>2</Sub>S</ListItem><ListItem>1c: X = O</ListItem><ListItem>1d: X = H, OH</ListItem><ListItem>1e: X = 2H</ListItem></UnorderedLists>
Active components utilized against pyrimidine deaminases from mammalian tissues (mouse kidney and human liver) showed optimum advantage when compared with tetrahydrouridine (THU).