Protease inhibitors human immunodeficiency virus

Fitzsimmons, M. E., Collins, J. M., Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4 potential contribution to high first-pass metabolism, Drug. Metab. Dispos. 1997, 25, 256-266. 

Leonard, S., Van Schepdael, A., Ivanyi, T., Lazar, L, Rosier, J., Vanstockem, M., Vermeersch, H., and Hoogmartens, J. (2005). Development of a capillary electrophoretic method for the separation of diastereoisomers of a new human immunodeficiency virus protease inhibitor. Electrophoresis 26, 627-632. 

Chiba M, Hensleigh M, Nishime JA, Balani SK, Lin JH. Role of C5dochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos 1996 24(3) 307-314. 

Koudriakova T, latsimirskaia E, Utkin I, et al. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5 mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos 1998 26(6) 552-561. 

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. 

Since the discovery of cis-1 -amino-2-indanol as a ligand for human immunodeficiency virus protease inhibitors and the development of a practical industrial process for the synthesis of either ris-isomers in enantiopure form, the remarkable properties of the rigid indane platform have been used extensively in an ever-increasing number of asymmetric methodologies. In addition to the use of this amino alcohol as a chiral auxiliary and ligand for asymmetric synthesis, it has found application as a useful resolution agent. Applications include amines, carboxylic acids, and alcohols. 

Burger and his colleagues have illustrated an example of bridging different populations with PK/PD modeling to assess the dose adjustment need. They compared the PK/PD relationships of indinavir, a human immunodeficiency virus protease inhibitor, with or without ritonavir, in HIV-infected Thai patients to those in Caucasian patients, and recommended no dose adjustment despite the general lower body weight in the Thai population. ... 

Sadler BM, Gillotin C, Lou Y, Eron JJ, Lang W, Haubrich R, Stein DS. Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir. Antimicrob Agents Chemother 2001 45(12) 3663-8. 

Gregoor PJ, van Gelder T, van der Ende ME, Ijzermans JN, Weimar W. Cyclosporine and triple-drug treatment with human immunodeficiency virus protease inhibitors. Transplantation 1999 68(8) 1210. 

Moyle GJ, Youle M, Higgs C, Monaghan J, Prince W, Chapman S, Clendeninn N, Nelson MR. Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus. J CUn Pharmacol 1998 38(8) 736-43. 

Striker R, Conlin D, Marx M, Wiviott L. Localized adipose tissue hypertrophy in patients receiving human immunodeficiency virus protease inhibitors. Clin Infect Dis I998 27(l) 218-20. 

Bornhovd E, Sakrauski AK, Bruhl H, WaUi R, Plewig G, Rocken M. Mmtiple circumscribed subcutaneous lipomas associated with use of human immunodeficiency virus protease inhibitors Br J Dermatol 2000 143(5) 1H3-14. 

Sheikh AM, Wolf DC, Lebovics E, Goldberg R, Horowitz HW. Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels. Transplantation 1999 68(2) 307-9. 

Lillibridge JH, Liang BH, Kerr BM, et al. Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Disp. 1998 26 609-616. 

One of the few industrial examples of the asymmetric synthesis of halohy-drins is in a process to the human immunodeficiency virus protease inhibitor, Indinavir [146], The 7,5 unsaturated carboxamide 10 is smoothly converted into iodohydrin 11 (92%, 94% de) (Scheme 20) [147]. 

A wide variety of simple transformations on chiral pool materials can lead to unnatural amino acid derivatives. This is illustrated by the Pictet-Spengler reaction of L-phenylalanine, followed by amide formation and reduction of the aromatic ring (Scheme 18) [43]. The resultant amide 12 is an intermediate in a number of commercial human immunodeficiency virus protease inhibitors. 

D. Hickman, S. Vasavanonda, G. Nequist, L. Colletti, W. M. Kati, R. Bertz, A. Hsu, and D. J. Kempf, Estimation of serum-free 50-percent inhibitory concentrations for human immunodeficiency virus protease inhibitors lopinavir and ritonavir. Antimicrob Agents Chemother 48 2911-2917 (2004). 

B. M. Sadler, C. Gillotin, Y. Lou, and D. S. Stein, In vivo effect of alpha-l-acid glycoprotein on pharmacokinetics of amprenavir, a human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 45 852-856 (2001). 

As shown in Fig. 15-37, a chiral intermediate for a human immunodeficiency virus protease inhibitor (H1VPI) was also synthesized by the reduction of an a-chloroketone with a Streptomyces strain [198L... 

Robinson BS, Riccardi KA, Gong YF, et al. BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can he used in combination with other available antiretroviral agents. Antimicrobial Agents and Chemotherapy 44(8), 2093, 2000. 

The benzyl protection group can be applied to primary amines. In the Romero et al. synthesis of HIV-1 (human immunodeficiency virus) protease inhibitors, the aniline unit in 128 was treated with excess benzyl bromide to give the V,V-dibenzyl derivative 129 in 89% yield.The alkyl fragment was elaborated in six steps to give 130. Catalytic hydrogenation with a palladium on carbon catalyst removed both benzyl groups to give aniline derivative 131 in 90% yield. 

Poppe SM, Slade DE, Chong K-T, et al. Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997 41 1058-1063. 

Hsu A Granneman GR, Cao G, Carodiers L, El-Shourbagy T, Baroldi P, Erdman K, Brown F, Sun E, Leonard JM. Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir. Clin Pharmacol Ther (1998) 63,453-64. 

---