Peptidomimetic inhibitors of HIV protease

Current Topics in Medicinal Chemistry

Volumn 4, Issue 10, 2004, Pages 1079-1095

  Randolph, John T ^a   DeGoey, David A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; AMPRENAVIR; AMPRENAVIR PHOSPHATE; ANTIRETROVIRUS AGENT; ATAZANAVIR; BILIRUBIN; CYTOCHROME P450; DARUNAVIR; DIDANOSINE; DPC 681; DPC 684; EFAVIRENZ; GLUCOSE; INDINAVIR; INSULIN; LAMIVUDINE; LIPID; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; PLACEBO; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; STAVUDINE; SULFONAMIDE; TMC 126; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIDOVUDINE;

ANTIBIOTIC RESISTANCE; CLINICAL TRIAL; DIARRHEA; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG STRUCTURE; ENZYME INHIBITION; FOOD DRUG INTERACTION; GASTROINTESTINAL DISEASE; GLUCOSE INTOLERANCE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERBILIRUBINEMIA; HYPERLIPIDEMIA; IMMUNE RESPONSE; INSULIN RESISTANCE; LIPOATROPHY; LIPOHYPERTROPHY; NAUSEA AND VOMITING; NEPHROLITHIASIS; NONHUMAN; PATIENT COMPLIANCE; QUANTITATIVE ANALYSIS; REVIEW; TREATMENT FAILURE; TREATMENT OUTCOME; VIRUS DETECTION; VIRUS LOAD;

ANTI-HIV AGENTS; CARBAMATES; CLINICAL TRIALS; DIPEPTIDES; HIV; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; INDINAVIR; MODELS, MOLECULAR; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; NELFINAVIR; OLIGOPEPTIDES; PEPTIDES; PHENYLBUTYRATES; PHOSPHORIC ACID ESTERS; PYRIDINES; PYRIMIDINONES; RITONAVIR; SAQUINAVIR; SULFONAMIDES; URETHANE;

EID: 3042554178     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568026043388330     Document Type: Review

References (144)

1. Palella, F. J. Jr.; Delaney, K. M.; Moorman, A. C.; Loveless, M. O.; Fuhrer, J.; Satten, G. A.; Aschman, D. J.; Holmberg, S. D. Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection. N. Engl. J. Med. 1998, 338, 853-860.
2. Collier, A. C.; Coombs, R. W.; Schoenfeld, D. A.; Bassett, R. L.; Timpone, J.; Baruch, A.; Jones, M.; Facey, K.; Whitacre, C.; McAuliffe, V. J.; Friedman, H. M.; Merigan, T. C.; Reichman, R. C.; Hooper, C.; Corey, L. Treatment of Human Immunodeficiency Virus Infection with Saquinavir, Zidovudine, and Zalcitabine. N. Engl. J. Med. 1996, 334, 1011-1017.
3. Cameron, D. W.; Heath-Chiozzi, M.; Danner, S.; Cohen, C.; Krabcik, S.; Maurath, C.; Sun, E.; Henry, D.; Rode, R.; Potoff, A.; Leonard, J. Randomised Placebo-Controlled Trial of Ritonavir in Advanced HIV-1 Disease. Lancet 1998, 351, 543-549.
4. Hammer, S. M.; Squires, K. E.; Hughes, M. D.; Grimes, J. M.; Demeter, L. M.; Currier, J. S.; Eron, J. J.; Feinberg, J. E.; Balfour, H. H.; Dayton, L. R.; Chodakewitz, J. A.; Fischl, M. A. A Controlled Trial of 2 Nucleoside Analogs Plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or Less. N. Engl. J. Med. 1997, 337, 725-733.
5. Eron, J. J., Jr. HIV-1 Protease Inhibitors. Clin. Infect. Diseases 2000, 30, S160-S170.
6. Garcia-Lerma, J. G.; Heneine, W. Resistance of Human Immunodeficiency Virus Type 1 to Reverse Transcriptase and Protease Inhibitors: Genotypic and Phenotypic Testing. J. Clin. Virol. 2001, 21, 197-212.
7. Molla, A.; Korneyeva, M.; Gao, Q.; Vasavanonda, S.; Schipper, P. J.; Mo, H.-M.; Markowitz, M.; Chernyavskiy, T.; Niu, P.; Lyons, N.; Hsu, A.; Granneman, G. R.; Ho, D. D.; Boucher, C. A. B.; Leonard, J. M.; Norbeck, D. W.; Kempf, D. J. Ordered Accumulation of Mutations in HIV Protease Confers Resistance to Ritonavir. Nat. Med. 1996, 2, 760-766.
8. Carpenter, C. C. J.; Cooper, D. A.; Fischl, M. A.; Gatell, J. M.; Gazzard, B. G.; Hammer, S. M.; Hirsch, M. S.; Jacobsen, D. M.; Katzenstein, D. A.; Montaner, J. S. G.; Richman, D. D.; Saag, M. S.; Schechter, M.; Schooley, R. T.; Thompson, M. A.; Vella, S.; Yeni, P. G.; Volberding, P. A. Antiretroviral Therapy in Adults: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 2000, 283, 381-390.
9. Darke, P. L.; Nutt, S. F.; Brady, S. F.; Garsky, V. M.; Ciccarone, T. M.; Leu, C.-T.; Lumma, P. K.; Freidinger, R. M.; Veber, D. F.; Sigal, I. S. HIV-1 Protease Specificity of Peptide Cleavage is Sufficient for Processing of gag and pol Polyproteins. Biochem. Biophys. Res. Commun. 1988, 156, 297-303.
10. Debouck, C.; Gorniak, J. G.; Strickler, J. E.; Meek, T. D.; Metcalf, B. W.; Rosenberg, M. Human Immunodeficiency Virus Protease Expressed in Escherichia coli Exhibits Autoprocessing and Specific Maturation of the gag Precursor. Proc. Natl. Acad. Sci. USA 1987, 84, 8903-8906.
11. Kohl N. E.; Emini E.A.; Schleif, W.A.; Davis, L. J.; Heimbach, J. C.; Dixon, R. A. F.; Scolnick, E. M.; Sigal, I. S. Active Human Immunodeficiency Virus Protease is Required for Viral Infectivity. Proc. Natl. Acad. Sci. USA 1988, 85, 4686-4690.
12. Kempf, D. J.; Sham., H. L. HIV Protease Inhibitors. Curr. Pharm. Des. 1996, 2, 225-246.
13. Flexner, C. HIV Protease Inhibitors. N. Engl. J. Med. 1998, 338, 1281-1292.
14. Kempf, D. J.; Molla, A.; Hsu, A. Protease Inhibitors as Anti-Human Immunodeficiency Virus Agents. In Antiviral Theapy; De Clercq, E.; Ed.; ASM Press: Washington, D. C., 2001, pp. 147-173.
15. Adkins, J. C.; Faulds, D. Amprenavir. Drugs 1998, 55, 837-842.
16. Mangum, E.; Graham, K. K. Lopinavir-Ritonavir: a New Protease Inhibitor. Pharmacother. 2001, 21, 1352-1363.
17. Sham, H. L.; Kempf, D. J.; Molla, A.; Marsh, K. C.; Kumar, G. N.; Chen, C.-M.; Kati, W.; Stewart, K.; Lal, R.; Hsu, A.; Betebenner, D.; Korneyeva, M.; Vasavanonda, S.; McDonald, E.; Saldivar, A.; Wideburg, N.; Chen, X.; Niu, P.; Park, C.; Jayanti, V.; Grabowski, B.; Granneman, G. R.; Sun, E.; Japour, A. J.; Leonard, J. M.; Plattner, J. J.; Norbeck, D. W. ABT-378, a Highly Potent Inhibitor of the Human Immunodeficiency Virus Protease Antimicrob. Agents Chemother. 1998, 42, 3218-3224.
18. Lebon, F.; Ledecq, M. Approaches to the Design of Effective HIV-1 Protease Inhibitors. Curr. Med. Chem. 2000, 7, 455-477.
19. Kaldor, S. W.; Kalish, V. J.; Davies, J. F.; Shetty, B. V.; Fritz, J. E.; Appelt, K.; Burgess, J. A.; Campanale, K. M.; Chirgadze, N. Y.; Clawson, D. K.; Dressman, B. A.; Hatch, S. D.; Khalil, D. A.; Kosa, M. B.; Lubbehusen, P. P.; Muesing, M. A.; Patrick, A. K.; Tatlock, J.; Reich, S. H.; Su, K. H.; Tatlock, J. H. Viracept (nelfinavir mesylate, AG1343): a Potent, Orally Bioavailable Inhibitor of HIV-1 Protease. J. Med. Chem. 1997, 40, 3979-3985.
20. Wlodawar, A.; Guschina, A. Structural and Biochemical Studies of Retroviral Proteases. Biochim. Biophys. Acta 2000, 1477, 16-34.
21. Meek, T. D.; Lambert, D. M.; Dreyer, G. B.; Carr, T. J.; Tomaszek, T. A., Jr.; Moore, M. L.; Strickler, J. E.; Debouck, C.; Hyland, L. J.; Matthews, T. J.; Metcalf, B. W.; Petteway, S. R. Inhibition of HIV-1 Protease in Infected T-Lymphocytes by Synthetic Peptide Analogs. Nature 1990, 343, 90-92.
22. Rusconi, S.; Catamancio, S. L. S. HIV-1 Protease Inhibitors in Development. Expert Opin. Invest. Drugs 2002, 11, 387-395.
23. Jain, R. G.; Furfine, E. S.; Pedneault, L.; White, A. J.; Lenhard, J. M. Metabolic Complications Associated with Antiretroviral Therapy. Antiviral Res. 2001, 51, 151-177.
24. Molla, A.; Granneman, G. R.; Sun, E.; Kempf, D. J. Recent Developments in HIV Protease Inhibitor Therapy. Antiviral Res. 1998, 39, 1-23.
25. Moyle, G. J.; Back, D. Principles and Practice of HIV-Protease Inhibitor Pharmacoenhancement. HIV Medicine 2001, 2, 105-113.
26. Thompson, L. A.; Tebben, A. J., Pharmacokinetics and Design of Aspartyl Protease Inhibitors. Annual Reports in Med. Chem. 2001, 36, 247-256.
27. Tavel, J. A. Ongoing Trials in HIV Protease Inhibitors. Expert Opin. Investig. Drugs 2000, 9, 917-928.
28. Kitchen, V. S.; Skinner, C.; Ariyoshi, K.; Lane, A. E.; Duncan, I. B.; Burckhardt, J.; Burger, H. U.; Bragman, K.; Pinching, A. J.; Wever, J. N. Safety and Activity of Saquinavir in HIV Infection. Lancet 1995, 345, 952-955.
29. Roberts, N. A.; Martin, J. A.; Kinchington, D.; Broadhurst, A. V., Craig, J. C.; Duncan, I. B.; Galpin, S. A.; Handa, B. K.; Kay, J.; Krohn, A.; Lambert, R. W.; Merrett, J. H.; Mills, J. S.; Parkes, K. E. B.; Redshaw, S.; Ritchie, A. J.; Taylor, D. L.; Thomas, G. J.; Machin, P. J. Rational Design of Peptide-Based HIV Proteinase Inhibitors. Science 1990, 248, 358-361.
30. Duncan, I. B.; Redshaw, S. Discovery and Early Development of Saquinavir. Infect. Dis. Ther. 2002, 25, 27-47.
31. Hoetelmans, R. M. W.; Meenhorst, P. L.; Mulder, J. W.; Burger, D. M.; Koks, C. H. W.; Beijnen, J. H. Clinical Pharmacology of HIV Protease Inhibitors: Focus on Saquinavir, Indinavir, and Ritonavir. Pharmacy World and Science 1997, 19, 159-175.
32. Kempf, D. J.; Marsch, K. C.; Kumar, G.; Rodriques, A. D.; Denissen, J. F.; McDonald, E.; Kukulka, M. J.; Hsu, A.; Granneman, G. R.; Baroldi, P. A.; Sun, E.; Pizzuti, D.; Plattner, J. J.; Norbeck, D. W.; Leonard, J. M. Pharmacokinetic Enhancement of Inhibitors of the Human Immunodeficiency Virus Protease by Coadministation with Ritonavir. Antimicrob. Agents Chemother. 1997, 41, 654-660.
33. Kilby, J. M.; Sfakianos, G.; Gizzi, N.; Siemon-Hryczyk, P.; Ehrensing, E.; Oo, C.; Buss, N.; Saag, M. S. Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative Adults. Antimicrob. Agents Chemother. 2000, 44, 2672-2678.
34. Raredes, R.; Puig, T.; Arno, A.; Negredo, E.; Balague, M.; Bonjoch, A.; Jou, A.; Tuldra, A.; Tural, C; Sirera, G.; Veny, A.; Romeu, J.; Ruiz, L.; Clotet, B. High-Dose Saquinavir Plus Ritonavir: Long-Term Efficacy in HIV Positive Protease Inhibitor-Experienced Patients and Predictors of Virologic Response. J. Acquir. Immune Defic. Syndr. 1999, 22, 132.
35. Tebas, P.; Patick, A. K.; Kane, E. M.; Klebert, M. K.; Simpson, J. H.; Erice, A.; Powderly, W. G.; Henry, K. Virological Responses to a Ritonavir-Saquinavir-Containing Regimen in Patients Who Had Previously Failed Nelfinavir. AIDS 1999, 13, F23-F28.
36. Cardiello, P. G.; van Heeswijk, R. P.; Hassink, E. A.; Srasuebkul, P.; Mahanontharit, A.; Samor, T. M.; Worarien, W.; Beijnen, J. H.; Hoetelmans, R. M.; Ruxrungtham, K.; Cooper, D. A.; Lange, J. M.; Phanuphak, P. Simplifying Protease Inhibitor Therapy with Once-Daily Dosing of Saquinavir Soft-Gelatin Capsules/Ritonavir (1600/100 mg): HIVNAT 001.3 Study. J. Acquir. Immune Defic. Syndr. 2002, 29, 464-470.
37. Dorsey, B. D.; Levin, R. B.; McDaniel, S. L.; Vacca, J. P.; Guare, J. P.; Darke, P. L.; Zugay, J. A.; Emini, E. A.; Schleif, W. A.; Quintero, J. C.; Lin, J. H.; Chen, I.-W.; Holloway, M. K.; Fitzgerald, P. M. D.; Axel, M. G.; Ostovic, D.; Anderson, P. S.; Huff, J. R. L-735,524: The Design of a Potent and Orally Bioavailable HIV Protease Inhibitor. J. Medicinal Chemistry 1994, 37, 3443-3451.
38. Vacca, J. P.; Dorsey, B. D.; Schleif, W. A.; Levin, R. B.; McDaniel, S. L.; Darke, P. L.; Zugay, J.; Quintero, J. C.; Blahy, O. M.; Roth, E.; Sardana, V. V.; Schlabach, A. J.; Graham, P. I.; Condra, J. H.; Gotlib, L.; Holloway, M. K.; Lin, J.; Chen, I.-W.; Vastag, K.; Ostovic, D.; Anderson, P. S.; Emini, E. A.; Huff, J. R. L-735,524: An Orally Bioavailable Human Immunodeficiency Virus Type I Inhibitor. Proc. Natl. Acad. Sci. 1994, 91, 4096-4100.
39. Burger, D. M.; Hugen, P. W. H.; Aarnoutse, R. E.; Dieleman, J. P.; Prins, J. M.; van der Poll, T.; ten Veen, J. H.; Mulder, J. W.; Meenhorst, P. L.; Blok, W. L.; van der Meer, J. T. M.; Reiss, P.; Lange, J. M. A. A Retrospective, Cohort-Based Survey of Patients Using Twice-Daily Indinavir + Ritonavir Combinations: Pharmacokinetics, Safety, and Efficacy. J. Acquir. Immune Defic. Syndr. 2001, 26, 218-224.
40. Rockstroh, J. K.; Bergmann, F.; Wiesel, W.; Rieke, A.; Theisen, A.; Fatkenheuer, G.; Oette, M.; Carls, H.; Fenske, S.; Nadler, M.; Knechten H. Efficacy and Safety of Twice Daily First-Line Ritonavir/Indinavir Plus Double Nucleoside Combination Therapy in HIV-Infected Individuals. AIDS 2000, 14, 1181-1185.
41. Solas, C.; Basso, S.; Poizot-Martin, I.; Ravaux, I.; Gallais, H.; Gastaut, J.-A.; Durand, A.; Lacarelle, B. High Indinavir Cmin Is Associated with Higer Toxicity in Patients on Indinavir-Ritonavir 800/100 mg Twice-Daily Regimen. J. Acquir. Immune Defic. Syndr. 2002, 29, 374-377.
42. Kempf, D. J.; Sham, H. L.; Marsh, K. C.; Flentge, C. A.; Betebenner, D.; Green, B. E.; McDonald, E.; Vasavanonda, S.; Saldivar, A.; Wideburg, N. E.; Kati, W. M.; Ruiz, L.; Zhao, C.; Fino, L.; Patterson, J.; Molla, A.; Plattner, J. J.; Norbeck, D. W. Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy. J. Med. Chem. 1998, 41, 602-617.
43. Kempf, D. J.; Marsh, K. C.; Denissen, J. F.; McDonald, E.; Vasavanonda, S.; Flentge, C. A.; Green, B. E.; Fino, L.; Park, C. H.; Kong, X.-P.; Wideburg, N. E.; Saldivar, A.; Ruiz, L.; Kati, W. M.; Sham, H. L.; Robins, T.; Stewart, K. D.; Hsu, A.; Plattner, J. J.; Leonard, J. M.; Norbeck, D. W. ABT-538 is a Potent Inhibitor of Human Immunodeficiency Virus Protease and Has High Oral Bio-availability in Humans. Proc. Natl. Acad. Sci. 1995, 92, 2484-2488.
44. Kempf, D. J.; Marsch, K. C.; Kumar, G.; Rodriques, A. D.; Denissen, J. F.; McDonald, E.; Kukulka, M. J.; Hsu, A.; Granneman, G. R.; Baroldi, P. A.; Sun, E.; Pizzuti, D.; Plattner, J. J.; Norbeck, D. W.; Leonard, J. M. Pharmacokinetic Enhancement of Inhibitors of the Human Immunodeficiency Virus Protease by Coadministation with Ritonavir. Antimicrob. Agents Chemother. 1997, 41, 654-660.
45. Becker, S. L.; Hoetelmans, M. W. Exploiting Pharmacokinetics to Optimize Antiretroviral Therapy. Updated in April, 2002. Published at http://www.medscape.com/viewarticle/416455.
46. Rathbun, R. C.; Rossi, D. R. Low-dose Ritonavir for Protease Inhibitor Pharmacokinetic Enhancement. Annals Pharmacother. 2002, 36, 702-706.
47. US Dept. of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. Washington, DC: US Dept. of Health and Human Services; February 4, 2002. Published at http://hivatis.org/trtgdlns.html.
48. Barry, M.; Mulcahy, F.; Merry, C.; Gibbons, S.; Back, D. Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin. Pharmacokinetics 1999, 36, 289-304.
49. Bardsley-Elliot, A.; Plosker, G. L. Nelfinavir: An Update on its Use in HIV Infection. Drugs 2000, 59, 581-620.
50. Saag, M. S.; Tebas, P.; Sension, M.; Conant, M.; Myers, R.; Chapman, S. K.; Anderson, R.; Clendeninn, N. Randomized, Double-Blind Comparison of Two Nelfinavir Doses Plus Nucleosides in HIV-Infected Patients (Agouron Study 511). AIDS 2001, 15, 1971-1978.
51. Powderly, W. G.; Tebas, P. Nelfinavir, a New Protease Inhibitor: Early Clinical Results. AIDS 1999, 13 (Suppl. 1), S41-S48.
52. Easterbrook, P. J.; Newson, R.; Ives, N.; Pereira, S.; Moyle, G.; Gazzard, B. G. Comparison of Virologic, Immunologic, and Clinical Response to Five Different Initial Protease Inhibitor-Containing and Nevirapine-Containing Regimens. J. Acquir. Immune Defic. Syndr. 2001, 27, 350-364.
53. Kim, E. E.; Baker, C. T.; Dwyer, M. D.; Murcko, M. A.; Rao, B. G.; Tung, R. D.; Navia, M. A. J. Am. Chem. Soc. 1995, 117, 1181-1182.
54. Tung, R. D.; Livingston, D. J.; Rao, B. G.; Kim, E. E.; Baker, C. T.; Boger, J. S.; Chambers, S. P.; Deininger, D. D.; Dwyer, M.; Elsayed, L.; Fulghum, J.; Li, B.; Murcko, M. A.; Navia, M. A.; Novak, P.; Pazhanisamy, S.; Stuver, C.; Thomson, J. A. Design and synthesis of amprenavir, a novel HIV protease inhibitor. Infect. Dis. Ther. 2002, 25, 101-118.
55. Noble, S.; Goa, K. L. Amprenavir: A Review of its Clinical Potential in Patients with HIV Infection. Drugs 2000, 60, 1383-1410.
56. Eron, J. J.; Haubrich, R.; Lang, W.; Pagano, G.; Millard, J.; Wolfram, J.; Snowden, W.; Pedneault, L.; Tisdale, M. A phase II trial of dual protease inhibitor therapy: Amprenavir in combination with indinavir, nelfinavir, or saquinavir. J. Acquir. Immune Defic. Syndr. 2001, 26, 458-461.
57. Murphy, R. L.; Gulick, R. M.; DeGruttola, V.; D'Aquila, R. T.; Eron, J. J.; Sommadossi, J.-P.; Currier, J. S.; Smeaton, L.; Frank, I.; Caliendo, A. M.; Gerber, J. G.; Tung, R.; Kuritzkes, D. R. Treatment with Amprenavir Alone or Amprenavir with Zidovudine and Lamivudine in Adults with Human Immuno-deficiency Virus Infection. J. Infect. Dis. 1999, 179, 808-816.
58. Bart, P.-A.; Rizzardi, G. P.; Tambussi, G.; Chave, J.-P.; Chapuis, A. G.; Graziosi, C.; Corpataux, J.-M.; Halkic, N.; Meuwly, J.-Y.; Munoz, M.; Meylan, P.; Spreen, W.; McDade, H.; Yerly, S.; Perrin, L.; Lazzarin, A.; Pantaleo, G. Immunological and Virological Responses in HIV-1-Infected Adults at Early Stage of Established Infection Treated with Highly Active Antiretroviral Therapy. AIDS 2000, 14, 1887-1897.
59. Sale, M.; Sadler, B. M.; Stein, D. S. Pharmacokinetic Modeling and Simulations of Interaction of Amprenavir and Ritonavir. Antimicrob. Agents Chemother. 2002, 46, 746-754.
60. Acosta, E. P.; Kakuda, T. N.; Brundage, R. C.; Anderson, P. L.; Fletcher, C. V. Pharmacodynamics of Human Immunodeficiency Virus Type 1 Protease Inhibitors. Clin. Infect. Dis. 2000, 30, S151-S159.
61. John, L.; Marra, F.; Ensom, M. H. H. Role of therapeutic drug monitoring for protease inhibitors. Annals Pharmacother. 2001, 35, 745-754.
62. Back, D. J.; Khoo, S. H.; Gibbons, S. E.; Merry, C. The Role of Therapeutic Drug Monitoring (TDM) in Treatment of HIV Infection. Brit. J. of Clin. Pharmacol. 2001, 51, 301-308.
63. 1-Acid Glycoprotein on Pharmacokinetics of Amprenavir, a Human Immunodificiency Virus Protease Inhibitor. Antimicrob. Agents Chemother. 2001, 45, 852-856.
64. 1-Acid Glycoprotein on the Antiviral Efficacy of Human Immunodificiency Virus Protease Inhibitors. J. Infect. Dis. 1999, 180, 1833-1837.
65. Molla, A.; Vasavanonda, S.; Kumar, G.; Sham, H. L.; Johnson, M.; Grabowski, B.; Denissen, J. F.; Kohlbrenner, W.; Plattner, J. J.; Leonard, J. M.; Norbeck, D. W.; Kempf, D. J. Human Serum Attenuates the Activity of Protease Inhibitors Toward Wild-Type and Mutant Human Immunodificiency Virus. Virology 1998, 250, 255-262.
66. Sadler, B. M.; Stein, D. S. Clinical Pharmacology and Pharmacokinetics of Amprenavir. Annals Pharmacother. 2002, 36, 102-118.
67. Flexner, C. Dual Protease Inhibitor Therapy in HIV-Infected Patients: Pharmacologic Rationale and Clinical Benefits. Annu. Rev. Pharmacol. Toxicol. 2000, 40, 649-670.
68. Yu, K.; Daar, E. S. Dual Protease Inhibitor Therapy in the Management of the HIV-1. Expert Opin. Pharmacother. 2000, 1, 1331-1342.
69. Kumar, G. N.; Rodrigues, A. D.; Buko, A. M.; Denissen, J. F. Cytochrome P450-Mediated Metabolism of the HIV-1 Protease Inhibitor Ritonavir (ABT-538) in Human Liver Microsomes. J. Pharmacol. Exp. Ther. 1996, 277, 423-431.
70. Hsu, A.; Granneman, G. R.; Cao, G.; Carothers, L.; El-Shourbagy, T.; Baroldi, P.; Erdman, K.; Brown, F.; Sun, E.; Leonard, J. M. Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir. Clin. Pharmacol. Ther. 1998, 63, 453-464.
71. Cameron, D. W.; Japour, A. J.; Xu, Y.; Hsu, A.; Mellors, J.; Farthing, C.; Cohen, C.; Poretz, D.; Markowitz, M.; Follansbee, S.; Angel, J. B.; McMahon, D.; Ho, D.; Devanarayan, V.; Rode, R.; Salgo, M. P.; Kempf, D. J.; Granneman, R.; Leonard, J. M.; Sun, E. Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS 1999, 13, 213-224.
72. Buss, N.; Snell, P.; Bock, J.; Hsu, A.; Jorga, K. Saquinavir and Ritonavir Pharmacokinetics Following Combined Ritonavir and Saquinavir (Soft Gelatin Capsules) Administration. Brit. J. Clin. Pharmacol. 2001, 52, 255-264.
73. Saah, A. J.; Winchell, G. A.; Nessly, M. L.; Seniuk, M. A.; Rhodes, R. R.; Deutsch, P. J. Pharmocokinetic Profile and Tolerability of Indinavir-Ritonavir Combinations in Healthy Volunteers. Antimicrob. Agents. Chemother. 2001, 45, 2710-2715.
74. Mole, L.; Schmidgall, D.; Holodniy, M. A Pilot Trial of Indinavir, Ritonavir, Didanosine, and Lamivudine in a Once-Daily Four-Drug Regimen for HIV Infection. J. Acquir. Immune Defic. Syndr. 2001, 27, 260-265.
75. Lichterfeld, M.; Nischalke, H. D.; Bergmann, F.; Wiesel, W.; Rieke, A.; Theisen, A.; Fatkenheuer, G.; Oette, M.; Carls, H.; Fenske, S.; Nadler, M.; Knechten, H.; Wasmuth, J.-C.; Rockstroh, J. K. Long-term Efficacy and Safety of Ritonavir/Indinavir at 400/400 mg Twice a Day in Combination with Two Nucleoside Reverse Transcriptase Inhibitors as First Line Antiretroviral Therapy. HIV Med. 2002, 3, 37-43.
76. Sadler, B. M.; Piliero, P. J.; Preston, S. L.; Lloyd, P. P.; Lou, Y.; Stein, D. S. Pharmacokinetics and Safety of Amprenavir and Ritonavir Following Multiple-Dose Coadministration to Healthy Volunteers. AIDS 2001, 15, 1009-1018.
77. Sadler, B. M.; Gillotin, C.; Lou, Y.; Eron, J. J.; Lang, W.; Haubrich, R.; Stein, D. S. Pharmacokinetic Study of Human Immunodificiency Virus Protease Inhibitors used in Combination with Amprenavir. Antimicrob. Agents Chemother. 2001, 45, 3663-3668.
78. Boden, D.; Markowitz, M. Resistance to Human Immunodeficiency Virus Type 1 Protease Inhibitors. Antimicrob. Agents Chemother. 1998, 42, 2775-2783.
79. Miller, Veronica. Resistance to protease inhibitors. J. Acquir. Immune Defic. Syndr. 2001, 26, S34-S50.
80. Shafer, R. W. Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance. Clin. Microbiol. Rev. 2002, 15, 247-277.
81. Kempf, D. J.; Isaacson, J. D.; King, M. S.; Brun, S. C.; Xu, Y.; Real, K.; Berstein, B. M.; Japour, A. J.; Sun, E.; Rode, R. A. Identification of Genotypic Changes in Human Immunodeficiency Virus Protease that Correlate with Reduced Susceptibility to the Protease Inhibitor Lopinavir among Viral Isolates from Protease Inhibitor-Experienced Patients. J. Virology 2001, 75, 7462-7469.
82. Sugiura, W.; Matsuda, Z.; Yokomaku, Y.; Hertogs, K.; Larder, B.; Oishi, T.; Okano, A.; Shiino, T.; Tatsumi, M.; Matsuda, M.; Abumi, H.; Takata, N.; Shirahata, S.; Yamada, K.; Yoshikura, H.; Nagai, Y. Interference between D30N and L90M in selection and development of protease inhibitor-resistant human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 2002, 46, 708-715.
83. Hertogs, K.; Bloor, S.; Kemp, S. D.; Van den Eynde, C.; Alcorn, T. M.; Pauwels, R.; Van Houtte, M.; Staszewski, S.; Miller, V.; Larder, B. A. Phenotypic and Genotypic Analysis of Clinical HIV-1 Isolates Reveals Extensive Protease Inhibitor Cross-Resistance: A Survey of over 6000 Samples. AIDS 2000, 14, 1203-1210.
84. Schmidt B; Korn K; Moschik B; Paatz C; Uberla K; Walter H. Low Level of Cross-Resistance to Amprenavir (141W94) in Samples from Patients Pretreated with other Protease Inhibitors. Antimicrob. Agents Chemother. 2000, 44, 3213-6.
85. Duval, X.; Lamotte, C.; Race, E.; Descamps, D.; Damond, F.; Clavel, F.; Leport, C.; Peytavin, G.; Vilde, J.-L. Amprenavir Inhibitory Quotient and Virological Response in Human Immunodeficiency Virus-Infected Patients on an Amprenavir-Containing Salvage Regimen without or with Ritonavir. Antimicrob. Agents Chemother. 2002, 46, 570-574.
86. Kantor, R.; Fessel, W. J.; Zolopa, A. R.; Israelski, D.; Shulman, N.; Montoya, J. G.; Harbour, M.; Schapiro, J. M.; Shafer, R. W. Evolution of Primary Protease Inhibitor Resistance Mutations during Protease Inhibitor Salvage Therapy. Antimicrob. Agents Chemother. 2002, 46, 1086-1092.
87. Hirsch, M. S.; Brun-Vezinet, F.; D'Aquila, R. T.; Hammer, S. M.; Johnson, V. A.; Kuritzkes, D. R.; Loveday, C.; Mellors, J. W.; Clotet, B.; Conway, B.; Demeter, L. M.; Vella, S.; Jacobsen, D. M.; Richman, R. D. Antiretroviral Drug Resistance Testing in Adult HIV-1 Infection. JAMA 2000, 283, 2417-2426.
88. Renu, G. J.; Furfane, E. S.; Pedneault, L.; While, A. J.; Lenhard, J. M. Metabolic Complications Associated with Antiretroviral Therapy. Antiviral Res. 2001, 51, 151-177.
89. Holstein, A.; Plaschke, A.; Egberts, E.-H. Lipodystrophy and Metabolic Disorders as Complication of Antiretroviral Therapy of HIV Infection. Exp. Clin. Endocrinol. Diabetes 2001, 109, 389-392.
90. Hruz, P. W.; Murata, H.; Muekler, M. Adverse Metabolic Consequences of HIV Protease Inhibitor Therapy: the Search for a Central Mechanism. Amer. J. Physiol. 2001, 280, E549-E553.
91. Behrens, G. M.; Stoll, M.; Schmidt, R. E. Lipodystrophy Syndrome in HIV Infection: what is it, what Causes it and how can it be Managed? Drug Saf. 2000, 23, 57-76.
92. Graham, N. M. Metabolic Disorders among HIV-Infected Patients Treated with Protease Inhibitors: A Review. J. Acquir. Immune Defic. Syndr. 2000, 25 (Suppl. 1), S4-S11.
93. Murata, H.; Hruz, P. W.; Mueckler, M. Investigating the Cellular Targets of HIV Protease Inhibitors: Implication for Metabolic Disorders and Improvements in Drug Therapy. Curr. Drug Targets: Infect. Disorders 2002, 2, 1-8.
94. Serghides, L.; Nathoo, S.; Walmsley, S.; Kain, K. C. CD36 Deficiency Induced by Antiretroviral Therapy. AIDS 2002, 16, 353-358.
95. Galli, M.; Ridolfo, A. L.; Adorni, F.; Gervasoni, C.; Ravasio, L.; Corsico, L.; Gianelli, E.; Piazza, M.; Vaccarezza, M.; Monforte, A. d'A; Moroni, M. Body Habitus Changes and Metabolic Alterations in Protease Inhibitor-Naive HIV-1-Infected Patients Treated with Two Nucleoside Reverse Transcriptase Inhibitors. J. Acquir. Immune Defic. Syndr. 2002, 29, 21-31.
96. Segerer, S.; Bogner, J. R.; Walli, R.; Loch, O.; Goebel, F. D. Hyperlipidemia under Therapy with Protease Inhibitors. Infection 1999, 27, 77-81.
97. Mulligan, K.; Grunfeld, C.; Tai, V. W.; Algren, H.; Pang, M. Y.; Chernoff, D. N.; Lo, J. C.; Schambelan, M. Hyperlipidemia and Insulin Resistance are Induced by Protease Inhibitors Independent of Changes in Body Composition in Patients with HIV Infection. J. Acquir. Immune Defic. Syndr. 2000, 23, 35-43.
98. Moyle, G. J.; Lloyd, M.; Reynolds, B.; Baldwin, C.; Madalia, S.; Gazzard, B. G. Dietary Advice with or without Prevastatin for the Management of Hypercholesterolaemia Associated with Protease Inhibitor Therapy. AIDS, 2001, 15, 1503-1508.
99. Calza, L.; Manfredi, R.; Chiodo, F. Use of Fibrates in the Management of Hyperlipidemia in HIV- Infected Patients Receiving HAART. Infection 2002, 30, 26-31.
100. Mallon, P. W. G. Switch Therapy Studies. J. HIV Ther. 2001, 6, 45-48.
101. Carr, A.; Hudson, J.; Chuah, J.; Mallal, S.; Law, M.; How, J.; Doong, N.; French, M.; Smith, D.; Cooper, D. A. HIV Protease Inhibitor Substitution in Patients with Lipodystrophy: a Randomized, Controlled, Open-Label, Multicenter Study. AIDS 2001, 15, 1811-1822.
102. Coplan, P. M.; Nikas, A. A.; Leavitt, R. Y.; Doll, L.; Nessly, M. L.; DiNubile, M. J.; Guess, H. A. Indinavir did not Increase the Short-Term Risk of Adverse Cardiovascular Events Relative to Nucleoside Reverse Transcriptase Inhibitor Therapy in Four Phase III Clinical Trials. AIDS, 2001, 15, 1584-1586.
103. Walli, R.; Herfort, O.; Michl, G. M.; Demant, T.; Jager, H.; Dieterle, C.; Bogner, J. R.; Landgraf, R.; Goebel, F. D. Treatment with Protease Inhibitors Associated with Peripheral Insulin Resistance and Impaired Oral Glucose Tolerance in HIV-1-Infected Patients. AIDS 1998, 12, F167-F173.
104. Zucker, S. D.; Xiaofa, Q.; Rouster, S. D.; Yu, F.; Green, R. M.; Keshavan, P.; Feinberg, J.; Sherman, K. E. Mechanism of Indinavir-Induced Hyperbilirubinemia. Proc. Nat. Acad. Sci. 2001, 98, 12671-12676.
105. Stoll, V.; Qin, W.; Stewart, K. D.; Jakob, C.; Park, C.; Walter, K.; Simmer, R. L.; Helfrich, R.; Bussirre, D.; Kao, J.; Kempf, D.; Sham, H. L.; Norbeck, D. W. X-ray Crystallographic Structure of ABT-378 (Lopinavir) Bound to HIV-1 Protease. Bioorg. Med. Chem. Lett. 2002, 10, 2803-2806.
106. Sham, H. L.; Betebenner, D. A.; Chen, X.; Saldivar, A.; Vasavanonda, S.; Kempf, D. J.; Plattner, J. J.; Norbeck, D. W. Synthesis and Structure-Activity Relationships of a Novel Series of HIV-1 Protease Inhibitors Encompassing ABT-378 (Lopinavir). Bioorg. Med. Chem. Lett. 2002, 12, 1185-1187.
107. Kempf, D. J. Discovery and Early Development of Ritonavir and ABT-378. In Protease Inhibitors in AIDS Therapy; Ogden, R. C.; Flexner, C. W.; Eds.; Marcel Dekker: New York, 2000; pp 49-64.
108. Hurst, M.; Faulds, D. Lopinavir. Drugs 2000, 60, 1371-1379.
109. Murphy, R. L.; Brun, S.; Hicks, C.; Eron, J. J.; Gulick, R.; King, M.; White, A. C., Jr.; Benson, C.; Thompson, M.; Kessler, H. A.; Hammer, S.; Bertz, R.; Hsu, A.; Japour, A.; Sun, E. ABT-378/Ritonavir Plus Stavudine and Lamivudine for the Treatment of Antiretroviral-Naive Adults with HIV-1 Infection: 48-Week Results. AIDS 2001, 15, F1-F9.
110. Benson, C. A.; Deeks, S. G.; Brun, S. C.; Gulick, R. M.; Eron, J. J.; Kessler, H. A.; Murphy, R. L.; Hicks, C.; King, M.; Wheeler, D.; Feinberg, J.; Stryker, R.; Sax, P. E.; Riddler, S.; Thompson, M.; Real, K.; Hsu, A.; Kempf, D.; Japour, A. J.; Sun, E. Safety and Antiviral Activity at 48 Weeks of Lopinavir/Ritonavir Plus Nevirapine and 2 Nucleoside Reverse-Transcriptase Inhibitors in Human Immunodeficiency Virus Type 1-Infected Protease Inhibitor-Experienced Patients. J. Infect. Dis. 2002, 185, 599-607.
111. Walmsley, S.; Bernstein, B.; King, M.; Arribas, J.; Beall, G.; Ruane, P.; Johnson, M.; Johnson, D.; Lalonde, R.; Japour, A.; Brun, S.; Sun, E. Lopinavir-Ritonavir versus Nelfinavir for the Initial Treatment of HIV Infection. New Engl. J. Med. 2002, 346, 2039-2046.
112. Prado, J. G.; Wrin, T.; Beauchaine, J.; Ruiz, L.; Petropoulos, C. J.; Frost, S. D. W.; Clotet, B.; D'Aquila, R. T.; Martinez-Picado, J. Amprenavir-Resistant HIV-1 Exhibits Lopinavir Cross-Resistance and Reduced Replication Capacity. AIDS 2002, 16, 1009-1017.
113. Kempf, D. J.; Isaacson, J. D.; King, M. S.; Brun, S. C.; Sylte, J.; Richards, B.; Bernstein, B.; Rode, R.; Sun, E. Analysis of the Virologic Response with Respect to Baseline Viral Phenotype and Genotype in Protease Inhibitor-Experienced HIV-1-Infected Patients Receiving Lopinavir/Ritonavir Therapy. Antiviral Ther. 2002, In Press.
114. Faessler, A.; Bold, G.; Capraro, H.-G.; Cozens, R.; Mestan, J.; Poncioni, B.; Roesel, J.; Tintelnot-Blomley, M.; Lang, M. Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability. J. Med. Chem. 1996, 39, 3203-3216.
115. Sham, H. L.; Zhao, C.; Stewart, K. D.; Betebenner, D. A.; Lin, S.; Park, C. H.; Kong, X.-P.; Rosenbrook, W. Jr.; Herrin, T.; Madigan, D.; Vasavanonda, S.; Lyons, N.; Molla, A.; Saldivar, A.; Marsch, K. C.; McDonald, E.; Wideburg, N. E.; Denissen, J. F.; Robins, T.; Kempf, D. J.; Plattner, J. J.; Norbeck, D. W. A Novel, Picomolar Inhibitor of Human Immunodeficiency Virus Type 1 Protease. J. Med. Chem. 1996, 39, 392-397.
116. Bold, G.; Faessler, A.; Capraro, H.-G.; Cozens, R.; Klimkait, T.; Lazdins, J.; Mestan, J.; Poncioni, B.; Roesel, J.; Stover, D.; Tintelnot-Blomley, M.; Acemoglu, F.; Beck, W.; Boss, E.; Eschbach, M.; Huerlimann, T.; Masso, E.; Roussel, S.; Ucci-Stoll, K.; Wyss, D.; Lang, M. New Aza-Dipeptide Analogs as Potent and Orally Absorbed HIV-1 Protease Inhibitors: Candidates for Clinical Development. J. Med. Chem. 1998, 41, 3387-3401.
117. Xu, Z.; Singh, J.; Schwinden, M. D.; Zheng, B.; Kissick, T. P.; Patel, B.; Humora, M. J.; Quiroz, F.; Dong, L.; Hsieh, D.-M.; Heikes, J. E.; Pudipeddi, M.; Lindrud, M. D.; Srivastava, S. K.; Kronenthal, D. R.; Mueller, R. H. Process Research and Development for an Efficient Synthesis of the HIV Protease Inhibitor BMS-232632. Org. Process Res. Devel. 2002, 6, 323-328.
118. Robinson, B. S.; Riccardi, K. A.; Gong, Y.-F.; Guo, Q.; Stock, D. A.; Blair, W. S.; Terry, B. J.; Deminie, C. A.; Djang, F.; Colonno, R. J.; Lin, P.-F. BMS-232632, a Highly Potent Human Immunodeficiency Virus Protease Inhibitor that can be Used in Combination with Other Available Antiretroviral Agents. Antimicrob. Agents Chemother. 2000, 44, 2093-2099.
119. Drusano, G. L.; Bilello, J. A.; Preston, S. L.; O'Mara, E.; Kaul, S.; Schnittman, S.; Echols, R. Hollow-Fiber Unit Evaluation of a New Human Immunodeficiency Virus Type 1 Protease Inhibitor, BMS-232632, for Determination of the Linked Pharmacodynamic Variable. J. Infect. Dis. 2001, 183, 1126-1129.
120. Gong, Y.-F.; Robinson, B. S.; Rose, Ronald E.; Deminie, C.; Spicer, T. P.; Stock, D.; Colonno, R. J.; Lin, P.-F. In Vitro Resistance Profile of the Human Immunodeficiency Virus Type 1 Protease Inhibitor BMS-232632. Antimicrob. Agents Chemother. 2000, 44, 2319-2326.
121. Sorbera, L. A.; Martin, L.; Castaner, J.; Castaner, R. M. Fosamprenavir. Anti-HIV HIV Protease Inhibitor. Drugs Future 2001, 26, 224-231.
122. Ghosh, A. K.; Thompson, W. J.; Fitzgerald, P. M. D.; Culberson, J. C.; Axel, M. G.; McKee, S. P.; Huff, J. R.; Anderson, P. S. Structure-Based Design of HIV-1 Protease Inhibitors: Replacement of Two Amides and a 10π-Aromatic System by a Fused Bis-Tetrahydrofuran. J. Med. Chem. 1994, 37, 2506-2508.
123. Ghosh, A. K.; Kincaid, J. F.; Walters, D. E.; Chen, Y.; Chaudhuri, N. C.; Thompson, W. J.; Culberson, C.; Fitzgerald, P. M. D.; Lee, H. Y.; McKee, S. P.; Munson, P. M.; Duong, T. T.; Darke, P. L.; Zugay, J. A.; Schleif, W. A.; Axel, M. G.; Lin, J.; Huff, J. R. Nonpeptidal P2 Ligands for HIV Protease Inhibitors: Structure-Based Design, Synthesis, and Biological Evaluation. J. Med. Chem. 1996, 39, 3278-3290.
124. Ghosh, A. K.; Kincaid, J. F.; Cho, W.; Walters, D. E.; Krishnan, K.; Hussain, K. A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J. Potent HIV Protease Inhibitors Incorporating High-Affinity P2-Ligands and (R)-[(hydroxyethyl)amino]sulfonamide Isostere. Bioorg. Med. Chem. Lett. 1998, 8, 687-690.
125. Ghosh, A. K.; Pretzer, E.; Cho, H.; Hussain, K. A.; Duzgunes, N. Antiviral Activity of UIC-PI, a Novel Inhibitor of the Human Immunodeficiency Virus Type 1 Protease. Antiviral Res. 2002, 54, 29-36.
126. Yoshimura, K.; Kato, R.; Kavlick, M. F.; Nguyen, A.; Maroun, V.; Maeda, K.; Hussain, K. A.; Ghosh, A. K.; Gulnik, S. V.; Erickson, J. W.; Mitsuya, H. A Potent Human Immunodeficiency Virus Type 1 Protease Inhibitor, UIC-94003 (TMC-126), and Selection of a Novel (A28S) Mutation in the Protease Active Site. J. Virology 2002, 76, 1349-1358.
127. Kaltenbach, R. F., III; Trainor, G.; Getman, D.; Harris, G.; Garber, S.; Cordova, B.; Bacheler, L.; Jeffrey, S.; Logue, K.; Cawood, P.; Klabe, R.; Diamond, S.; Davies, M.; Saye, J.; Jona, J.; Erickson-Viitanen, S. DPC 681 and DPC 684: Potent, Selective Inhibitors of Human Immunodeficiency Virus Protease Active Against Clinically Relevant Mutant Variants. Antimicrob. Agents Chemother. 2001, 45, 3021-3028.
128. Humphrey, R. W.; Wyvill, K. M.; Nguyen, B.-Y.; Shay, L. E.; Kohler, D. R.; Steinberg, S. M.; Ueno, T.; Fukasawa, T.; Shintani, M.; Hayashi, H.; Mitsuya, H.; Yarchoan, R. A Phase I Trial of the Pharmacokinetics, Toxicity, and Activity of KNI-272, an Inhibitor of HIV-1 Protease, in Patients with AIDS or Symptomatic HIV Infection. Antiviral Res. 1999, 41, 21-33.
129. Balden, E. T.; Bhat, T. N.; Gulnik, S.; Liu, B.; Topol, I. A.; Kiso, Y.; Mimoto, T.; Mitsuya, H.; Erickson, J. W. Structure of HIV-1 Protease with KNI-272, a Tight-Binding Transition-State Analogue Containing Allophenylnorstatine. Structure 1995, 3, 581-590.
130. Mimoto, T.; Kato, R.; Takaku, H.; Nojima, S.; Terashima, K.; Misawa, S.; Fukazawa, T.; Ueno, T.; Sato, H.; Shintani, M.; Kiso, Y.;
131. Yoshimura, K.; Kato, R.; Yusa, K.; Kavlick, M. F.; Maroun, V.; Nguyen, A.; Mimoto, T.; Ueno, T.; Shintani, M.; Falloon, J.; Masur, H.; Hayashi, H.; Erickson, J.; Mitsuya, H. JE-2147: A Dipeptide Protease Inhibitor (PI) that Potently Inhibits Multi-PI-Resistant HIV-1. Proc. Natl. Acad. Sci. USA 1999, 96, 8675-8680.
132. Reiling, K. K.; Endres, N. F.; Dauber, D. S.; Craik, C. S.; Stroud, R. M. Anisotropic Dynamics of the JE-2147-HIV Protease Complex: Drug Resistance and Thermodynamic Binding Mode Examined in a 1.09 A Structure. Biochem. 2002, 41, 4582-4594.
133. Cheng, Y.; Rano, T. A.; Huening, T. T.; Zhang, F.; Lu, Z.; Schleif, W. A.; Gabryelski, L.; Olsen, D. B.; Stahlhut, M.; Kuo, L. C.; Lin, J. H.; Xu, X.; Jin, L.; Olah, T. V.; McLoughlin, D. A.; King, R. C.; Chapman, K. T.; Tata, J. R. A Combinatorial Library of Indinavir Analogues and Its In Vitro and In Vivo Studies. Bioorg. Med. Chem. Lett. 2002, 12, 529-532.
134. Beaulieu, P. L.; Anderson, P. C.; Cameron, D. R.; Croteau, G.; Gorys, V.; Grand-Maitre, C.; Lamarre, D.; Liard, F.; Paris, W.; Plamondon, L.; Soucy, F.; Thibeault, D.; Wernic, D.; Yoakim, C.; Pav, S.; Tong, L. 2′,6′-Dimethylphenoxyacetyl: A New Achiral High Affinity P3-P2 Ligand for Peptidomimetic-Based HIV Protease Inhibitors. J. Med. Chem. 2000, 43, 1094-1108.
135. Le, V.-D.; Mak, C. C.; Lin, Y.-C.; Elder, J. H.; Wong, C.-H. Structure-Activity Studies of FIV and HIV Protease Inhibitors Containing Allophenylnorstatine. Bioorg. Med. Chem. 2001, 9, 1185-1195.
136. Muhlman A; Classon B; Hallberg A; Samuelsson B Synthesis of Potent C(2)-Symmetric, Diol-Based Hiv-1 Protease Inhibitors. Investigation of Thioalkyl and Thioaryl P1/P1′ Substituents. J. Med. Chem. 2001, 44, 3402-3406.
137. Pyring D; Lindberg J; Rosenquist A; Zuccarello G; Kvarnstrom I; Zhang H; Vrang L; Unge T; Classon B; Hallberg A; Samuelsson B. Design and Synthesis of Potent C(2)-Symmetric Diol-Based HIV-1 Protease Inhibitors: Effects of Fluoro Substitution. J. Med. Chem. 2001, 44, 3083-3091.
138. Spaltenstein, A.; Almond, M. R.; Bock, W. J.; Cleary, D. G.; Furfine, E. S.; Hazen, R. J.; Kazmierski, W. M.; Salituro, F. G.; Tung, R. D.; Wright, L. L. Novel Inhibitors of HIV Protease: Design, Synthesis and Biological Evaluation of Picomolar Inhibitors Containing Cyclic P1/P2 Scaffolds. Bioorg. Med. Chem. Lett. 2000, 10, 1159-1162.
139. May, B. C. H.; Abell, A. D. alpha-Methylene Tetrazole-Based Peptidomimetics: Synthesis and Inhibition of HIV Protease. J. Chem. Soc., Perkin Trans. 1 2002, 172-178.
140. Edmonds, M. K.; Abell, A. D. Design and Synthesis of a Conformationally Restricted Trans Peptide Isostere Based on the Bioactive Conformations of Saquinavir and Nelfinavir. J. Org. Chem. 2001, 66, 3747-3752.
141. Mak, C. C.; Le, V.-D.; Lin, Y.-C.; Elder, J. H.; Wong, C.-H. Design, Synthesis, and Biological Evaluation of HIV/FIV Protease Inhibitors Incorporating a Conformationally Constrained Macrocycle with a Small P3′ Residue. Bioorg. Med. Chem. Lett. 2001, 11, 219-222.
142. Tyndall, J. D. A.; Reid, R. C.; Tyssen, D. P.; Jardine, D. K.; Todd, B.; Passmore, M.; March, D. R.; Pattenden, L. K.; Bergman, D. A.; Alewood, D.; Hu, S.-H.; Alewood, P. F.; Birch, C. J.; Martin, J. L.; Fairlie, D. P. Synthesis, Stability, Antiviral Activity, and Protease-Bound Structures of Substrate-Mimicking Constrained Macrocyclic Inhibitors of HIV-1 Protease. J. Med. Chem. 2000, 43, 3495-3504.
143. Marastoni, M.; Bazzaro, M.; Salvadori, S.; Bortolotti, F.; Tomatis, R. HIV-1 Protease Inhibitors Containing an N-Hydroxyamino Acid Core Structure. Bioorg. Med. Chem. 2001, 9, 939-945.
144. Dohnalek, J.; Hasek, J.; Duskova, J.; Petrokova, H.; Hradilek, M.; Soucek, M.; Konvalinka, J.; Brynda, J.; Sedlacek, J.; Fabry, M. Hydroxyethylamine Isostere of an HIV-1 Protease Inhibitor Prefers Its Amine to the Hydroxy Group in Binding to Catalytic Aspartates. A Synchrotron Study of HIV-1 Protease in Complex with a Peptidomimetic Inhibitor. J. Med. Chem. 2002, 45, 1432-1438.