Protease inhibitors amprenavir

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

Protease inhibitors (amprenavir, Increase or decrease serum levels of estrogen Decrease efficacy of COCs or increase... 

Protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir) Rifampin... 

Azalides azithromycin Azoles fluconazole, itraconazole, ketoconazole, and voriconazole Macrolides erythromycin, clarithromycin Protease inhibitors amprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, and saquinavir Quinolones ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin. 

E. J. Corey, E-Y. Zhang, re and si-Face-Selective Nitroal-dol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478) , Angew. Chern. Int. Ed 1999, 38,1931-1934. 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

Protease inhibitors amprenavir indinavir sulfate nelfinavir ritonavir... 

Furfine, E. S., Baker, C. T., Hale, M. R., Reynolds, D. J., Salisbury, J. A., Searle, A. D., Studenberg, S. D., Todd, D., Tung, R. D., and Spaltenstein, A. (2004). Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob. Agents Chemother. 48 791-798. 

Use of an organocatalyst in a highly diastereoselective nitroaldol reaction was reported by the Corey group in the synthesis of 123 [128]. This compound is a key building block in the synthesis of the HIV-protease inhibitor amprenavir. The alkaloid-based fluoride salt, 122, was used as an efficient chiral phase-transfer catalyst (this type of catalyst was developed by the same group [129-131]) and led to formation of the (2R,3S) diastereomer (2H,3S)-123 in 86% yield and with a diastereo-meric ratio of d.r. = 17 1 (Scheme 6.53) [128], It is worthy of note that a much... 

BMECs have been used to study various aspects of the P-gp-mediated efflux of compounds from the endothelial cells that comprise the BBB. Several examples have demonstrated the usefulness of this system to study polarized efflux via P-gp. For example, the influence of P-gp expressed in brain capillary endothelial cells on the transport of cyclosporin A (388,389), vincristine (381), protease inhibitors (amprenavir, saquinavir, and indinavir) (245,390), rhodamine 123 (211,383), opioid peptides (211,391,392), and the (1-blocking agent bunitrolol (393) have all been determined using this system. 

Amprenavir [am PREN a veer] Like other protease inhibitors, amprenavir is used in combination with a least two nucleoside reverse transcriptase inhibitors. Its long plasma half-life permits twice daily dosing, but the large size and number of capsules per day (16) day may reduce patient compliance. The drug may be less well tolerated than some other protease inhibitors and it is unclear whether amprenavir offers any clinical advantages over other protease inhibitors. 

FLECAINIDE ANTIVIRALS - PROTEASE INHIBITORS Amprenavir, ritonavir and possibly saquinavir and tipranavir with ritonavir t flecainide levels, with risk of ventricular arrhythmias Uncertain possibly inhibition of CYP3A4- and CYP2D6-mediated metabolism of flecainide Manufacturers recommend avoiding co-administration of flecainide with amprenavir, ritonavir and saquinavir... 

The micelle-forming molecule TPGS is an effective vehicle for lipid-based drug delivery, and is also a water-soluble source of the water-insoluble oil Vitamin [16] jjjY protease inhibitor, amprenavir,... 

Sadler BM, Gillotin C, Lou Y, Stein DS. Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing. Antimicrob Agents Chemother 2001 45(l) 30-7. 

L. Dickinson, L. Robinson, J. Tjia, S. Khoo, D. Back, Simultaneous determination of HIV protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir in human plasma by LC—AdS dS, J. Chromatogr. B, 829... 

In a study in 18 healthy subjects, the pharmacokinetics of hoth indinavir 800 mg three times daily and voriconazole 200 mg twice daily were unaffected hy at least a week of concurrent use. However, in vitro studies suggest that the metaholism of HfV-protease inhihitors may he inhihited hy voriconazole, and the metaholism of voriconazole may he inhihited hy HTV-protease inhibitors. The manufacturer therefore suggests that patients should be carefully monitored for evidence of drug toxicity and/or loss of efficacy during concurrent use of other HIV-protease inhibitors (amprenavir, neliinavir and saquinavir are specifically mentioned). ... 

Fosampienavir is an oral prodrug of the protease inhibitor amprenavir, with a reduced daily dose. Since this is a prodrag, any analysis in biological fluids would be measuring amprenavir. Therefore, HPLC methods as described for amprenavir would apply... 

Combination of 16 ARVs seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfmavir, ritonavir, and saquinavir), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine), and two nonnucleoside reverse transcriptase inhibitors (efavirenz and nevirapine)... 

Chiral (S)-3-formyl-tetrahydrofuran can be converted into (S)-3-hydroxyfuran via Baeyer-VUliger oxidation (Scheme 4.92). The latter is a key intermediate for the synthesis of the HIV protease inhibitor amprenavir (GlaxoSmithKline). 

Scheme 4.92 Possible synthesis of the HIV protease inhibitor amprenavir starting from (S)-3-formyl-tetrahydrofuran.

DaiUy, E. Thomas, L. Kergueris, M.F. JolUet, P. Bourin, M. High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelflnavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction, J.Chromatogr.B, 2001, 758, 129-135. 

Poirier, J.-M. Radembino, N. Robidou, P. JaUlon, P. Simultaneous determination of the five HIV-protease inhibitors Amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir in human plasma by sohd-phase extraction and column liquid chromatography, Ther.Drug Monit., 2000,22, 465-473. 

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