Abstract:
:A number of biologically active nucleoside analogues contain the adenine isostere 4-amino-pyrrolo[2,1-f][1,2,4]triazine connected to various sugar moieties through a C-C anomeric linkage. We employed palladium-catalyzed cross-coupling chemistry to promptly functionalize the 7-position of such a heterocyclic scaffold with various alkynyl and aryl groups starting from a common 7-iodo-pyrrolotriazine C-ribonucleoside intermediate. Analogues bearing a 7-cyclopropyl-, 7-propyl-, and 7-butylacetylene moiety displayed potent cytotoxic activity, with the latest being the most selective of this series toward cancer cells. Further insights revealed that such C-nucleosides could exert their antiproliferative action by causing dose-dependent DNA damage.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Li Q,Groaz E,Persoons L,Daelemans D,Herdewijn Pdoi
10.1021/acsmedchemlett.0c00269subject
Has Abstractpub_date
2020-07-09 00:00:00pages
1605-1610issue
8issn
1948-5875journal_volume
11pub_type
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