1. Academic Validation
  2. Synthesis and Antitumor Activity of C-7-Alkynylated and Arylated Pyrrolotriazine C-Ribonucleosides

Synthesis and Antitumor Activity of C-7-Alkynylated and Arylated Pyrrolotriazine C-Ribonucleosides

  • ACS Med Chem Lett. 2020 Jul 9;11(8):1605-1610. doi: 10.1021/acsmedchemlett.0c00269.
Qingfeng Li 1 Elisabetta Groaz 1 Leentje Persoons 2 Dirk Daelemans 2 Piet Herdewijn 1
Affiliations

Affiliations

  • 1 Medicinal Chemistry, KU Leuven, Rega Institute for Medical Research, Herestraat 49-box 1041, 3000 Leuven, Belgium.
  • 2 Laboratory of Virology and Chemotherapy, KU Leuven, Rega Institute for Medical Research, Herestraat 49-box 1043, 3000 Leuven, Belgium.
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.

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