The treatment of viral infectious diseases such as AIDS and Hepatitis C has witnessed spectacular progress in the recent past. By exploiting similar modes of pharmaceutical action (Scheme 1), various new nucleotide analogs (e.g. Tenofovir and Sofosbuvir) have been added to a growing list of antiviral and cytostatic drugs. It is our aim to provide you with antiviral and cytostatic nucleotide derivatives suitable for
Scheme 1: Metabolism and pharmaceutical effects of antiviral and cytostatic nucleoside derivatives follow similar mechanisms[5,6]. Nucleosides or their corresponding prodrugs enter the cytosol by active transport through the cell membrane where they undergo phosphorylation and/or further modification by cellular enzymes. The triphosphorylated products are incorporated into nucleic acids during replication or transcription, resulting in chain termination or mutagenesis.
Please refer to the following list of new lead compounds. In most cases custom-made derivatizations such as (poly)phosphorylation will be accessible.
|Tenofovir / Tenofovir diphosphate||Human Immunodeficiency Virus (HIV)-1/ Hepatitis B Virus (HBV)|
|Emtricitabine* / Emtricitabine-5′-O-triphosphate*||HIV-1/-2|
(Sofosbuvir* nucleoside and corresponding phosphates)
|Hepatitis C Virus (HCV)|
|Penciclovir*||Herpes Simplex Virus (HSV)|
|Famciclovir*||Varicella Zoster Virus (VZV)|
| Kulkarni et al. (2016) A Complex Network of Interactions between S282 and G283 of Hepatitis C Virus Nonstructural Protein 5B and the Template Strand Affects Susceptibility to Sofosbuvir and Ribavirin. Antimicrob. Agents Chemother. 60 (4):2018.|
Incorporation of Ribavirin-TP by RNA-dependent RNA-polymerase NS5B of HCV
| Rawson et al. (2016) 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2'-Deoxycytidine. Antimicrob. Agents Chemother. 60 (4):2318.|
Elucidation of the molecular mechanism of 5-azacytidine in HIV-1 mutagenesis.
| Hollenbaugh et al. (2017) Substrates and Inhibitors of SAMHD1. PLoS One. 12 (1):e0169052.|
Kinetic characterization of SAMHD1 as a pontential drug target
| Huang et al. (2018) Clofarabine exerts antileukemic activity against cytarabine-resistant B-cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression. Cancer Med. 7 (4):1297.|
Description of a resistance mechanism against cytarabine in B‐cell precursor ALL (BCP‐ALL) treatment
 Jordheim et al. (2013) Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug. Discov. 12 (6):447.
 Cavaliere et al. (2017) Fluorinated nucleosides as an important class of anticancer and antiviral agents. Future Med. Chem. 9 (15):1809.