4113-98-8Relevant articles and documents
Synthesis and antiviral evaluation of sugar uracil-1-ylmethylhydrazones and their oxadiazoline derivatives
Ali, Omar M.,Amer, Hamada H.,Abdel-Rahman, Adel A.-H.
, p. 2823 - 2828 (2007)
1-Carbethoxymethyluracils have been synthesized and derivatized to the corresponding hydrazides, which were reacted with monosaccharides to afford the corresponding sugar hydrazones. Acetylation of the latter with acetic anhydride in pyridine, afforded the per-O-acetyl derivatives, while heating in acetic anhydride gave the corresponding oxadiazolines. The prepared compounds were tested for antiviral activity against hepatitis B virus and showed moderate activities. Georg Thieme Verlag Stuttgart.
Preliminary SAR and biological evaluation of potent HIV-1 protease inhibitors with pyrimidine bases as novel P2 ligands to enhance activity against DRV-resistant HIV-1 variants
Zhu, Mei,Ma, Ling,Zhou, Huiyu,Dong, Biao,Wang, Yujia,Wang, Zhen,Zhou, Jinming,Zhang, Guoning,Wang, Juxian,Liang, Chen,Cen, Shan,Wang, Yucheng
, (2019/11/28)
Introducing pyrimidine bases, the basic components of nucleic acid, to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2′ ligand, displayed remarkable enzyme inhibitory and antiviral activity, with the IC50 2.53 nM in vitro and a promising inhibition ratio with 68% against wild-type HIV-1 in vivo, with low cytotoxicity. This inhibitor also exhibited appreciable antiviral activity against DRV-resistant HIV-1 variants, which was of great value for further study.
Synthesis and RNA-Binding Properties of Extended Nucleobases for Triplex-Forming Peptide Nucleic Acids
Kumpina, Ilze,Brodyagin, Nikita,Mackay, James A.,Kennedy, Scott D.,Katkevics, Martins,Rozners, Eriks
, p. 13276 - 13298 (2019/10/16)
Triple-helix formation, using Hoogsteen hydrogen bonding of triplex-forming oligonucleotides, represents an attractive method for sequence-specific recognition of double-stranded nucleic acids. However, practical applications using triple-helix-forming oligonucleotides and their analogues are limited to long homopurine sequences. The key problem for recognition of pyrimidines is that they present only one hydrogen-bond acceptor or donor group in the major groove. Herein, we report our first attempt to overcome this problem by using peptide nucleic acids (PNAs) modified with extended nucleobases that form three hydrogen bonds along the entire Hoogsteen edge of the Watson-Crick base pair. New nucleobase triples (five) were designed, and their hydrogen bonding feasibility was confirmed by ab initio calculations. PNA monomers carrying the modified nucleobases were synthesized and incorporated in short model PNA sequences. Isothermal titration calorimetry showed that these nucleobases had a modest binding affinity for their double-stranded RNA (dsRNA) targets. Finally, molecular modeling of the modified triples in PNA-dsRNA helix suggested that the modest binding affinity was caused by subtle structural deviations from ideal hydrogen-bonding arrangements or disrupted π-stacking of the extended nucleobase scaffolds.
