Nucleotide reverse transcriptase inhibitors NRTIs

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) ... 

Raltegravir, or Isentress (1), is the first FDA-approved inhibitor of HIV integrase. HIV/AIDS drugs are categorized according to their mode of action as nucleoside and nucleotide reverse transcriptase inhibitors [NRTIs, e.g., tenofovir (2)], nonnucleotide reverse transcriptase inhibitors [NNRTIs, e.g., efavirenz (3)] protease inhibitors [Pis, e.g., ritonavir (4)], fusion inhibitors [e.g., enfuvirtide (5)], entry inhibitors... 

The 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 3) encompass a vast group of compounds that have been found active against HIV and HBV, although they have been primarily pursued for the treatment of HIV infections (AIDS). They are targeted at the HIV-associated reverse transcriptase (RT) and therefore also referred to as nucleoside reverse transcriptase inhibitors (NRTIs). They have to be distinguished from the nucleotide reverse transcriptase inhibitors (NtRTIs) such as adefovir (PMEA) and tenofovir (PMPA) (see above) which, like the NRTIs, act as chain... 

Nucleoside reverse transcriptase inhibitor (NRTI)/nucleotide reverse transcriptase inhibitor (NtRI) A modified version of a naturally-occurring nucleoside or nucleotide that prevents human immunodeficiency virus (HIV) replication by interfering with the function of the viral reverse transcriptase enzyme. The nucleoside/nucleotide analog causes early termination of the proviral DNA chain. For activity, an NRTI requires three phosphorylation steps once inside the cell, whereas an NtRI has a phosphate group attached and needs only two phosphorylation steps inside the cell for activity. 

Zidovudine (ZDV or AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) and it was the first anti-HIV agent to be introduced. Other NRTIs include stavudine (d4T), lamivudine (3TC), didano-sine (ddl), abacavir (ABC) and zalcitabine (ddC). Recent additions to this class are emtricitabine (FTC) which has a molecular structure similar to 3TC and tenofovir (TDF) a nucleotide reverse transcriptase inhibitor. 

The replicative cycle of HIV presents many opportunities for the targeting of antiviral agents. The drugs in clinical use are classified as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NTRTIs), and protease inhibitors (PI). 

Nucleoside reverse transcriptase inhibitors NRTIs are substrates for reverse transcriptase, which converts viral RNA into proviral DNA for incorporation into the host cell DNA. NRSIs are phosphorylated by host ceU enzymes to resemble normal nucleotides. When reverse transcriptase uses NRTI triphosphate instead of a nucleoside to form proviral DNA, the necessary chemical bonds cannot form and the DNA chain formed is left incomplete. 

Thumbnail Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Nucleotide Reverse Transcriptase Inhibitors (NtRTIs), NNRTI, Pis ... 

Nucleosides can be analysed by conventional reversed-phase (RP) LC with a buffered mobile phase. The separation of nucleotides is somewhat complicated by the dissociation of the phosphate groups and HINa exchange at these sites. As indicated for the phosphorylated anabolites of nucleoside reverse transcriptase inhibitors (NRTI, Ch. 13.2.4), ion-pair RPLC using 7V,7V-dimethylhexylamine (DMHA) can be applied to both reduce adduct formation and obtain sufficient retention [6-7]. Alternatively, enzymatic dephosphorylation of the nucleotides prior to LC-MS analysis can be performed. 

NRTI nucleoside/nucleotide reverse transcriptase inhibitor... 

Nonnucleoside RTIs that do not require metabolic activation (e.g., delavirdine and nevirapine, efavirenz, which are not myelosuppressants) and a nucleotide reverse-transcriptase inhibitor (adefovir) have been introduced. Resistance emerges rapidly if these drugs are used as individual agents for management of HIV infection. However, they may provide additive or synergistic activity against HIV if used in combination regimens with NRTIs and/or Pis. 

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nucleoside reverse transcriptase inhibitors (NRTIs) Nucleotide reverse transcriptase inhibitors Protease inhibitors... 

Adenine itself was successfully incorporated into a number of pharmaceuticals, Adefovir dipivoxil, also known as bis-POM PMEA, with trade names Preveon and Hepsera, is used for the treatment of hepatitis B and herpes simplex virus infection. It is an orally administered nucleotide analog as a reverse transcriptase inhibitor (NRTI). Reverse transcriptase is an enzyme crucial to viral production. A second NRXI that contains adenine is Tenofovir disoproxil fumarate (TDF), which has been used in the treatment of HIV/AIDS and hepatitis B. TDF is a prodrug of tenofovir (also known as PMPA) designed to improve absorption and cell permeability of the active moiety under the trade name Viread. Both adefovir dipivoxil and TDF are marketed by Gilead Sciences. 

NRTI nucleotide reverse transcriptase inhibitor pdta PE propylenediaminetetraacetic acid propyl ether... 

NRTI Nucleoside (or nucleotide) transcriptase inhibitor NNRTI Non-nucleoside reverse transcriptase inhibitor PI Protease inhibitor... 

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