| 論文名 |
9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: optimized preparation, including identification of by-products formed, and antiviral evaluation in vitro. |
| 著者 |
Marcela Kre?merov?
Petr Jansa
Martin Dra??nsk?
Petra S?zelov?
V?clav Ka?i?ka
Johan Neyts
Joeri Auwerx
Eleon?ra Kiss
Nesya Goris
George Stepan
Zlatko Janeba
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Bioorg Med Chem. 2013 Mar 1;21(5):1199-208. |
| WEBサイト |
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| 論文概要（和文） |
9- [2-（R）-（ホスホノメトキシ）プロピル] -2,6-ジアミノプリン（R）-PMPDAPとそのプロドラッグ：生成された副産物の同定とin Vitroでの抗ウイルス評価を含む最適化された準備。 |
| 論文概要（英文） |
New large-scale synthetic approach to antiretroviral agent 9-[2-(R)-(phosphonomethoxy)propyl]-2,6-diaminopurine, (R)-PMPDAP, was developed. Reaction of (R)-propanediol carbonate with 2,6-diaminopurine afforded exclusively (R)-9-(2-hydroxypropyl)-2,6-diaminopurine which was subsequently used for introduction of a phosphonomethyl residue using TsOCH(2)P(O)(OiPr)(2) or BrCH(2)P(O)(OiPr)(2) followed by deprotection of ester groups. All minor ingredients and by-products formed during the process were identified and further studied. The final product was obtained in high yield and its high enantiomeric purity (>99%) was confirmed by chiral capillary electrophoretic analysis using β-cyclodextrin as a chiral selector. Antiretroviral activity data of (R)-PMPDAP and its diverse prodrugs against HIV and FIV were investigated. Akin to (R)-PMPDAP, both prodrugs inhibit FIV replication in a selective manner. Compared to the parent molecule, the amidate prodrug was 10-fold less active against FIV in cell culture, whereas the alkoxyalkyl ester prodrug was 200-fold more potent in inhibiting FIV replication in vitro. |
