Ambrose Amalraj, Zemlicka Jiri, Kern Earl R, Drach John C, Gullen Elizabeth, Cheng Yung-Chi
Department of Chemistry, Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201-1379, USA.
Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1763-74. doi: 10.1080/15257770500266867.
The Z- and E-thymine and cytosine pronucleotides 3d, 4d, 3e, and 4e of methylenecyclopropane nucleosides analogues were synthesized, evaluated for their antiviral activity against human cytomegalovirus (HCMV), herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human immunodeficiency virus type 1 (HSV-1), and hepatitis B virus (HBV) and their potency was compared with the parent compounds 1d, 2d, 1e, and 2e. Prodrugs 3d and 4d were obtained by phosphorylation of parent analogues 1d or 2d with reagent 8. A similar phosphorylation of N4-benzoylcytosine methylenecyclopropanes 9a and 9b gave intermediates 11a and 11b. Deprotection with hydrazine in pyridine-acetic acid gave pronucleotides 3e and 4e. The Z-cytosine analogue 3e was active against HCMV and EBV The cytosine E-isomer 4e was moderately effective against EBV.
合成了亚甲基环丙烷核苷类似物的Z-和E-胸腺嘧啶及胞嘧啶前体核苷酸3d、4d、3e和4e，评估了它们对人巨细胞病毒（HCMV）、单纯疱疹病毒1型和2型（HSV-1和HSV-2）、水痘带状疱疹病毒（VZV）、爱泼斯坦-巴尔病毒（EBV）、人类免疫缺陷病毒1型（HSV-1）和乙型肝炎病毒（HBV）的抗病毒活性，并将它们的效力与母体化合物1d、2d、1e和2e进行了比较。前体药物3d和4d通过母体类似物1d或2d与试剂8磷酸化得到。N4-苯甲酰胞嘧啶亚甲基环丙烷9a和9b的类似磷酸化反应得到中间体11a和11b。在吡啶-乙酸中用肼脱保护得到前体核苷酸3e和4e。Z-胞嘧啶类似物3e对HCMV和EBV有活性。胞嘧啶E-异构体4e对EBV有中等效力。
