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Synthesis of novel fluoro analogues of MKC442 as microbicides.

Abstract：

:Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative of compound 5 using propagyl alcohol to afford compound 12 (YML220). The latter compound was selected for further studies since it showed the most potent and selective activity in vitro against wild-type HIV-1 and non-nucleoside reverse transcriptase inhibitor-, nucleoside reverse transcriptase inhibitor-, and protease inhibitor-resistant mutants and a wide range of HIV-1 clinical isolates. 12 also showed microbicidal activity in long-term assays with heavily infected MT-4 cells.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Loksha YM,Pedersen EB,Loddo R,Sanna G,Collu G,Giliberti G,La Colla P

doi

10.1021/jm500139a

subject

Has Abstract

pub_date

2014-06-26 00:00:00

pages

5169-78

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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