Antiviral and Cytostatic Evaluation of 5-(1-Halo-2-sulfonylvinyl)- and 5-(2-Furyl)uracil Nucleosides
Archiv der Pharmazie, 2017, 350(3-4): e1700023.
Transition metal-catalyzed halosulfonylation of 5-ethynyl uracil nucleosides provided (E)-5-(1-chloro-2-tosylvinyl)uridines. Tetrabutylammonium fluoride-mediated direct CH arylation of 5-iodouracil nucleosides with furan or 2-heptylfuran gave 5-furyl-substituted nucleosides without the necessity of using the organometallic substrates. These two classes of 5-substituted uracil nucleosides as well their corresponding ester derivatives were tested against a broad range of DNA and RNA viruses and the human immunodeficiency virus (HIV). The 3,5-di-O-acetyl-5-(E)-(1-chloro-2-tosylvinyl)-2-deoxyuridine (24) inhibited the growth of L1210, CEM and HeLa cancer cells in the lower micromolar range. The (-chloro)vinyl sulfone 24 and 5-(5-heptylfur-2-yl)-2-deoxyuridine (10) displayed micromolar activity against varicella zoster virus (VZV). The 5-(5-heptylfur-2-yl) analog 10 and its 3,5-di-O-acetyl-protected derivative showed similar activity against the cytomegalovirus (CMV). The 5-(fur-2-yl) derivatives of 2-deoxyuridine and arabino-uridine inhibited the replication of herpes simplex virus (HSV) TK strains while the 5-(5-heptylfur-2-yl) derivative 10 displayed antiviral activity against the parainfluenza virus.
Anticancer agents; Antiviral agents; Prodrugs; Pyrimidine nucleosides; Vinyl sulfones