New Isoxazolidine-Conjugates of QuinazolinonesSynthesis, Antiviral and Cytostatic Activity

作者：Piotrowska Dorota G^*; Andrei Graciela; Schols Dominique; Snoeck Robert; Grabkowska Druzyc Magdalena

来源：Molecules, 2016, 21(7): 959.

DOI：10.3390/molecules21070959

• phosphonate
• isoxazolidine
• quinazolinones
• antiviral
• cytostatic

A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC50 = 6.84, 15.29 and 9.44 M) toward VZV (TK+ strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC50 = 27-45 M). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC50 in the 21-102 M range.

• 出版日期2016-7
• 单位河北医科大学