Acyclic Nucleotide Analogues and Related Compounds

Abstract

Acyclic nuclwtide analogues bearing amino-and N-substituted amino groups in the side chain were prepared by alkylation of the bases with corresponding oxiranes and subsequent introduction of phosphonomethyl ether function. Novel enantiomeric synthons for the preparation of HPMP-compounds were prepared from a common intermediate and applied to syntheses of novel compounds (e.g. 8-azaguanine derivatives).

Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems

“…[14][15][16][17][18][19] On the other hand, modifications a purine unit were accomplished in several ways, for example, by construction of 8-azapurine analogs [1,2,3triazolo [4,5-d]pyrimidines] via replacement of C8 with the nitrogen atom. [20][21][22][23][24] Various 1-, 3-, or 7-deazapurine analogs were obtained by substitution of the respective nitrogen atoms of purine moiety by the methine group without changes of the steric demands in the newly formed systems (Figure 3). [25][26][27] For example, compound 1 exhibited inhibitory effect on the DNA viruses herpes simplex virus 1 (HSV-1), HSV-2, cytomegalovirus (CMV) (IC 50 ¼ 0.4-3.5 mg/mL), varicella zoster virus (VZV) (IC 50 ¼ 0.01-0.06 mg/ mL), vaccinia virus (IC 50 ¼ 0.7-2.0 mg/mL), and against the retroviruses Moloney murine sarcoma virus (MSV) (IC 50 ¼ 0.57-0.03 mg/mL), human immunodeficiency virus type 1 (HIV-1) and HIV-2 (IC 50 >0.8 mg/mL).…”