Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. vicriviroc binds specifically to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1 isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity against genetically diverse and drug-resistant HIV-1 isolates and was consistently more active than SCH-C in inhibiting viral replication. This compound demonstrated synergistic anti-HIV activity in combination with drugs from all other classes of approved antiretrovirals. Competition binding assays revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C. Functional assays, including inhibition of calcium flux, guanosine 5'-[35S]triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally, vicriviroc demonstrated diminished affinity for the human ether a-go-go related gene transcript ion channel compared to SCH-C, suggesting a reduced potential for cardiac effects. Vicriviroc represented a promising new candidate for the treatment of HIV-1 infection. Vicriviroc for HIV treatment was previously in Phase III studies but has since been discontinued.

Mimbane was developed by Parke-Davis as an analgesic. Information about the current use of the drug is not available.

Lodenosine is the experimental HIV reverse transcriptase inhibitor. It was designed as a chemically and enzymatically stable anti-AIDS drug. A phase II trial of the nucleoside analog lodenosine was suspended after one participant died and others showed signs of liver or kidney damage.

Tivirapine, also known as R-86183, is a HIV-1 specific reverse transcriptase inhibitor. It inhibits the replication of HIV-1, but not HIV-2, in a variety of CD4+ T-cell lines and peripheral blood lymphocytes. Whereas an HIV-1 strain containing the Leu-100-->Ile mutation in the RT gene is about 400-fold less susceptible, R86183 still inhibits the replication of an HIV-1 strain containing the Tyr-181-->Cys RT mutation by 50% at a concentration of 130 nM. Tivirapine had been in phase I clinical trial for the treatment of HIV-1 infection. However, this development was discontinued.

Ancriviroc (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. Ancriviroc is an orally bioavailable small molecule inhibitor of HIV-1 entry via CCR5 coreceptor interaction. Ancriviroc has potent activity against RANTES binding (K(i) = 2 nM), possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Ancriviroc had been in phase I clinical trials by Schering-Plough (subsidiary of Merck Sharp & Dohme) for the treatment of HIV infection. However, this research has been discontinued.

MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil) is a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Emivirine structurally is a nucleoside analog (NRTI) molecule, but it functions as a non-nucleoside reverse transcriptase inhibitor (NNRTI). Emivirine had reached phase 3 clinical trials for the treatment of HIV-1 infections before its further development was stopped.

Navuridine (AzddU) is a nucleoside analogue which demonstrated significant anti-HIV activity and low toxicity in preclinical studies. The drug was originally developed by University of Georgia. Navuridine is a dideoxyuridine inhibitor of HIV reverse transcriptase that is related to zidovudine. Navuridine exhibits a relatively short half-life and incomplete oral bioavailability and has not been developed into a clinical drug.

Didox is a simple, synthetic antioxidant and a ribonucleotide reductase inhibitor with activity against retroviruses. Didox inhibits retrovirus replication by depleting the deoxynucleotides obligatory for the synthesis of the proviral DNA intermediate of retrovirus replication. It also increases the radiosensitivity of cancer cells by inhibition of ribonucleotide reductase, resulting in a reduction of BCL-2 mediated resistance to apoptosis. Didox has been found to reduce the levels of oxidative injury markers in the brains of HIV patients with dementia. Didox has been evaluated in various phase I and phase II trials but Didox did not demonstrate any efficacy response in patients.

Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. Telbivudine is a synthetic thymidine nucleoside analogue; it is the L-isomer of thymidine. It is taken orally in a dose of 600 mg once daily with or without food. TYZEKA is the trade name for telbivudine, a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). The chemical name for telbivudine is 1-((2S,4R,5S)-4-hydroxy-5-hydroxymethyltetrahydrofuran-2-y1)-5-methyl-1H-pyrimidine-2,4-dione, or 1-(2-deoxy-β-L-ribofuranosyl)-5-methyluracil. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It is phosphorylated by cellular kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. Telbivudine 5'-triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'-triphosphate. Incorporation of telbivudine 5'-triphosphate into viral DNA causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine is an inhibitor of both HBV first strand (EC50 value = 1.3 ± 1.6 µM) and second strand synthesis (EC50 value = 0.2 ± 0.2 µM). Telbivudine 5'-triphosphate at concentrations up to 100 µM did not inhibit human cellular DNA polymerases α, β, or γ. No appreciable mitochondrial toxicity was observed in HepG2 cells treated with telbivudine at concentrations up to 10 µM.

Delavirdine is a nonnucleoside reverse transcriptase inhibitor (NNRTI). Delavirdine binds directly to reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DNA polymerase activities. Delavirdine does not compete with template:primer or deoxynucleoside triphosphates. HIV-2 RT and human cellular DNA polymerases alfa, gamma, or delta are not inhibited by delavirdine. In addition, HIV-1 group O, a group of highly divergent strains that are uncommon in North America, may not be inhibited by delavirdine. Delavirdine is marketed under the trade name Rescriptor, indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. .