کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2474726 | 1113159 | 2012 | 7 صفحه PDF | دانلود رایگان |

3-Hydroxymethyl-4-methyl-DCK (3, HMDCK) was discovered previously as a potent HIV non-nucleoside reverse transcriptase inhibitor (NNRTIs) (EC50: 0.004 μM, TI: 6225) with a novel mechanism of action. It exerts anti-HIV activity by inhibiting the production of HIV-1 double-stranded viral DNA from a single-stranded DNA intermediate, rather than blocking the generation of single-stranded DNA from a RNA template, which is the mechanism of action of current HIV-1 RT inhibitors. However, the insufficient metabolic stability of 3 limits its further clinical development. In the current study, a series of ester prodrugs of 3 was designed and synthesized to explore the new drug candidates as NNRTIs. The l-alanine ester prodrug 10 exhibited desirable pharmacokinetic properties in vitro and in vivo and showed improved oral bioavailability of 26% in rat, and would be a potential clinical candidate as a new anti-AIDS drug.
A series of ester prodrugs of 3-hydroxymethyl-4-methyl-DCK (3, HMDCK) was designed and synthesized to explore the new drug candidates as NNRTIs. The l-alanine ester prodrug 10 exhibited desirable pharmacokinetic properties in vitro and in vivo and showed improved oral bioavailability of 26% in rat, and would be a potential clinical candidate as a new anti-AIDS drug.Figure optionsDownload as PowerPoint slide
Journal: Acta Pharmaceutica Sinica B - Volume 2, Issue 2, April 2012, Pages 213–219