Synthesis and antiviral evaluation of novel 2,3-dihydroxypropyl nucleosides from 2- and 4-thiouracils.
Regioselective alkylation of 2-thiouracils 1a-c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-[[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio]pyrimidin-4(1H)-ones 3a-c and 4-[[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio] pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a-c and 9a,b whose deprotection afforded 6a-c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a-c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a-c and 15a,b which were deprotected to give 13a-c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a-c were treated with two equivalents of 2 to give 2,4-bis[[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio] pyrimidines 18a-c. Deprotection of compounds 18a-c gave 2,4-bis[(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.
Abdel-Rahman
Adel A-H
AA
Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt.
El-Etrawy
Abd-Allah Sh
AA
Abdel-Megied
Ahmed E-S
AE
Zeid
Ibrahim F
IF
El Ashry
El Sayed H
el SH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006515:Hepatitis B virus / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013889:Thiouracil / Q000737:chemistry*
D000998:Antiviral Agents; D009705:Nucleosides; D013889:Thiouracil