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AB - INK-20, a synthetic phosphocholine lipid-AZT conjugate, was evaluated for antiviral activity against wild-type HIV-1, a matched pair of pre-AZT and post-AZT and multidrug resistant clinical isolates. In addition, it was tested for activity against viruses resistant to nucleoside (AZT, 3TC) and nonnucleoside (nevirapine) reverse transcriptase and protease (saquinavir) inhibitors using the syncytial plaque reduction assay for infectious virus multiplication. The EC50 values were 0.004, and 0.005 μM against wild-type HIV-1 for INK-20 and AZT, respectively. INK-20 showed little or no cytotoxicity when assayed in CEM-SS cells and four other cell types including PBMC. This resulted in a selective index of > 25,000 and > 20,000 for INK-20 and AZT, respectively. When tested against a matched pair of pre-AZT and post-AZT clinical isolates, the EC50 values were 0.01 and 0.03 μM for INK-20 and 0.0005 and 0.33 μM for AZT, respectively. INK-20 had moderate to good activity against two other AZT resistant variants and very good activity against a multi-drug resistant clinical isolate compared to marked resistance of these viruses to AZT alone. INK-20 retained significant activity against viruses resistant to 3TC, nevirapine, and saquinavir. The synthetic phosphocholine lipid-AZT conjugate INK-20 represents a novel class of anti-HIV compounds, which may provide new strategies for the treatment of HIV drug-resistant variants.

Design and Synthesis of a Conformationally Restricted Trans Peptide Isostere Based on the Bioactive Conformations of Saquinavir and Nelfinavir.

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As part of HIV reproduction in an infected cell, newly synthesized viral proteins must be cut by a specific viral-induced HIV protease to form shorter proteins. An intensive research effort was made to design drugs that specifically inhibited this proteolytic enzyme, without affecting the proteolytic enzymes (like trypsin) that are needed by the host. In December 1995, saquinavir (brand names Invirase and Fortovase) was approved for the treatment of AIDS. This drug represented a new class of drugs known as protease inhibitors. Other protease inhibitors soon gained Food and Drug Administration (FDA) approval: ritonavir (Norvir), indinavir (Crixivan), and nelfinavir (Viracept).

ChemInform Abstract: Synthesis of the HIV-Proteinase Inhibitor Saquinavir: A Challenge for Process Research

Mutagenicity and genotoxicity studies, with and without metabolic activation where appropriate, have shown that saquinavir has no mutagenic activity in vitro in either bacterial (Ames test) or mammalian cells (Chinese hamster lung V79/HPRT test). Saquinavir does not induce chromosomal damage in vivo in the mouse micronucleus assay or in vitro in human peripheral blood lymphocytes, and does not induce primary DNA damage in vitro in the unscheduled DNA synthesis test.

synthesis essay Saquinavir. Valid point. I go there with my essay. Using it just to be there, without consideration of context or diction is lazy.