کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2474726 1113159 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prodrug design, synthesis and pharmacokinetic evaluation of (3′R, 4′R)-3-hydroxymethyl-4-methyl-3′, 4′-di-O-(S)-camphanoyl-(+)-cis-khellactone
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Prodrug design, synthesis and pharmacokinetic evaluation of (3′R, 4′R)-3-hydroxymethyl-4-methyl-3′, 4′-di-O-(S)-camphanoyl-(+)-cis-khellactone
چکیده انگلیسی

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

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Pharmaceutica Sinica B - Volume 2, Issue 2, April 2012, Pages 213–219
نویسندگان
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