کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1356741 | 981151 | 2008 | 9 صفحه PDF | دانلود رایگان |
Synthesis, in vitro anti-HIV activity, stability studies as well as potential for oral absorption of some novel phenyl S-acyl-2-thioethyl (SATE) phosphotriester derivatives of AZT (zidovudine; 3′-azido-2′,3′-dideoxythymidine) are described herein. These pronucleotides are characterized by the presence of polar functions on the SATE biolabile phosphate protections. Whereas derivatives incorporating an amino residue in the vicinity of the thioester functionality display low chemical stability, the introduction of one or two hydroxyl groups on the SATE moieties confers high resistance of the resulting prodrugs towards esterase hydrolysis. Thus, one of these pronucleotides, the monohydroxylated SATE derivative of AZT 2, is able to cross a Caco-2 cell monolayer mainly in intact form, probing that further development is warranted as a possible HIV-pronucleotide candidate.
A step further in the SATE mononucleotide prodrug approach.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 15, 1 August 2008, Pages 7321–7329