Antivirales

Alamifovir is an antiviral agent, which is synthetically derived. The mode of action of Alamifovir involves the inhibition of viral replication within host cells by targeting specific viral enzymes crucial for the replication process. This interference with the viral life cycle diminishes the ability of the virus to propagate and spread within the host organism. Alamifovir is primarily used in the treatment of viral infections, potentially offering therapeutic benefits for diseases caused by DNA viruses. Its effectiveness is contingent upon its ability to selectively target viral components with minimal cytotoxic effects on host cells, ensuring a beneficial therapeutic index. The applications of Alamifovir in antiviral therapy highlight its relevance in the continuous search for effective treatments against viral pathogens that pose significant clinical challenges. Research into Alamifovir's pharmacokinetics, safety profile, and resistance patterns is ongoing, with the aim of optimizing its use in clinical settings and expanding its utility across a broader spectrum of viral infections.

Applications Darunavir intermediate. References Ghosh, A., et al.: J. Med. Chem., 39, 3278 (1996), Ghosh, A., et al.: Bioorg. Med. Chem. Lett., 1998, 8, 687 (1998), Richman, D., et al.: Nature, 410, 995 (2001), Koh, Y., et al.: Antimicrob. Agents Chemother., 47, 3123 (2003),

LY2334737 is an orally available prodrug of gemcitabine with antineoplastic activity.

Applications A highly reactive thiol-specific spin-label. A specific conformational probe of thiol site structure by virtue of its minimal rotational freedom and distance from the covalent disulfide linkage to the macromolecule under study.

EIDD 2801 is an orally bioavailable prodrug of β-D-N4-hydroxycytidine and was shown to inhibit SARS-CoV-2 replication in human airway epithelial cells. EIDD 2801 was also tested in mice infected with SARS-CoV and MERS-CoV viruses. EIDD 2801 targets the RNA-dependent RNA polymerase (RdRp) and reduces virus titer and improved pulmonary function in experimental animals when used in prophylactic and therapeutic regime.

Applications Tenofovir (T018500) derivative.

Stability Hygroscopic Applications Cobicistat is a HIV protease inhibitor and has been coadministered with low-dose ritonavir (R535000) as a pharmacoenhancer, significantly increasing their plasma concentrations. References Von, H., Exp. Rev. Clin. Pharmacol., 5, 557 (2012); Lepist, E.I., et al.: Antimicrob. Agent. Chemother., 56, 5409 (2012); Orr, S.T.M., et al.: J. Med. Chem., 55, 4896 (2012);

CMP-5 is a PRMT5 inhibitor with antiviral activity, inhibits PRMT5 methyltransferase activity, and can be used in the study of SARS virus infection.

Azvudine hydrochloride (RO-0622 hydrochloride) is an NRTI inhibitor with antiviral activity, inhibiting HIV, HBV and HCV.

OSS_128167 (SIRT6-IN-1) is a specific SIRT6 inhibitor, and for SIRT6(IC50=89 μM), SIRT1(IC50=1578 μM) and SIRT2(IC50=751 μM).

Applications Atazanavir intermediate. Enantiomer S. References Vassar, R., et al.: Science, 286, 735 (1999), Maillard, M., et al.: J. Med. Chem., 50, 776 (2007), Stauffer, S., et al.: Bioorg. Med. Chem. Lett., 17, 1788 (2007),

Darunavir is a HIV-1 protease inhibitor used orally in the treatment of patients with multi-drug resistant HIV-1 infection (Ghosh, 2007). It has also been shown to be effective against other infectious diseases such as hepatitis C virus and SARS coronavirus. Metabolized by cytochrome P450 3A (CYP3A) isoenzymes, darunavir is often administered together with ritonavir that prolongs its bioavaiability, giving a terminal elimination half-life (t1/2) of 15 hours (Back, 2008). The effect of darunavir on natural compounds such as matrix proteins and toll-like receptor activity has also been studied via high performance liquid chromatography (HPLC) experiments.