Second generation HIV protease inhibitors against resistant virus

Expert Opinion on Drug Discovery

Volumn 3, Issue 7, 2008, Pages 775-786

  Lu, Zhijian ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

HIV; Mutations; Resistant virus; Second generation protease inhibitors

Indexed keywords

AMPRENAVIR; AMPRENAVIR PHOSPHATE; ANTIVIRUS AGENT; ARYLSULFONAMIDE DERIVATIVE; ATAZANAVIR; BRECANVIR; DARUNAVIR; ENFUVIRTIDE; ENZYME INHIBITOR; GW 0385; INDINAVIR; INDINAVIR DERIVATIVE; JE 2147; KNI 577; KNI 764; KYNOSTATIN 272; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; MOZENAVIR; NELFINAVIR; PL 100; PPL 100; PRODRUG; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; SULFONAMIDE; TIPRANAVIR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AREA UNDER THE CURVE; ATHEROGENESIS; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; CROSS RESISTANCE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DYSLIPIDEMIA; EPIDEMIC; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; LIPID BLOOD LEVEL; LIPODYSTROPHY; LOW DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; PRIORITY JOURNAL; REVIEW; SALVAGE THERAPY; SIDE EFFECT; VIRUS RESISTANCE;

EID: 48049108676     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.7.775     Document Type: Review

References (70)

1. Kempf DJ, Molla A, Hsu A. In: De Clercq E, editor, Antiretroviral therapy. ASM: Washingtobn DC; 2001. p. 147-74
2. Vacca JP, Condra JH. Clinically effective HIV protease inhibitors. Drug Discov Today 1997;2:261-72
3. Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997;337:734-9
4. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 1997;337:725-33
5. Condra J. Virological and clinical implications of resistance to HIV-1 protease inhibitors. Drug Resist Updates 1998;1:292-9
6. Boden D, Markowitz M. Resistance to human immunodeficiency virus type 1 protease inhibitors Antimicrob Agents Chemother 1998;42:2775-83
7. Deeks SG, Hecht FM, Swanson M, et al. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS 1999;13:F35-43
8. Lederberger B, Egger M, Opravil M, et al. Clinical progression and virological failure on highly active antiretroviral-drug therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet 1999;353:863-8
9. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virological failure and adverse drug reactions. Ann Intern Med 1999;131:81-7
10. Mocroft A, Ruiz L, Reiss P, et al. Virological rebound after suppression on highly active antiretroviral therapy. AIDS 2003;17:1741-51
11. Mastrolorenzo A, Rusconi S, Scozzafava A, et al. Inhibitors of HIV-1 protease: current state of the art 10 years after their introduction. From antiretroviral drugs to antifungal, antibacterial and antitumor agents based on aspartic protease inhibitors. Curr Med Chem 2007;14:2734-48
12. Luque I, Freire E. Structural parameterization of the binding enthalpy of small ligands. Proteins 2002;49:181-90
13. Luque I, Freire E. Structure-based prediction of binding affinities and molecular design of peptide ligands. Methods Enzymol 1998;295:100-27
14. Velazquez-Campoy A, Vega S, Freire E. Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes. Biochemistry 2002;41:8613-9
15. Velazquez-Campoy A, Muzammil S, Ohtaka H, et al. Structural and thermodynamic basis of resistance to HIV-1 protease inhibition: implications for inhibitor design. Curr Drug Targets Infect Disord 2003;3:311-28
16. Surleraux DL, Tahri A, Verschueren WG, et al. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. J Med Chem 2005;48:1813-22
17. Charpentier C, Lecossier D, Clavel F, Hance A. Role of resistance and fitness in driving the evolution of the protease in patients failing treatment with protease inhibitors [abstr. no. 601]. 10th Conf Retrovir Oppor Infect. Volume 10. 2003 February 10-14; Boston, USA
18. Erickson JW, Gulnik SV, Markowitz M. Protease inhibitors: resistance, cross-resistance, fitness and the choice of initial and salvage therapies. AIDS 1999;13(Suppl A):S189-204
19. Gatanaga H, Suzuki Y, Tsang H, et al. Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of high multitude of HIV-1 resistance against protease inhibitors. J Biol Chem 2002;277:5952-61
20. Quinones-Mateu ME, Arts EJ. Fitness of drug resistant HIV-1: methodology and clinical implications. Drug Resist Updat 2002;5:224-33
21. Logsdon BC, Vickrey JF, Martin P, et al. Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J Virol 2004;78:3123-32
22. Martin P, Vickrey JF, Proteasa G, et al. "Wide-open" 1.3 Å structure of a multidrug-resistant HIV-1 protease as a drug target. Structure 2005;13:1887-95
23. Martinez JL, Mcarthur R, Vickrey J, et al. The multi-drug resistance protease represents a novel drug target. 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy American Society of Microbiology; Washington DC, USA; 2004
24. Molla A, Komeyeva M, Gao Q, et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 1996;2:760-6
25. Robinson BS, Riccardi KA, Gong YF, et al. BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents. Antimicro Agents Chemother 2000;44:2093-9
26. Thaisrivongs S, Strohback JW. Structure-based discovery of tipranavir disodium (PNU-140690E): a potent, orally bioavailable, nonpeptidic HIV prote2se inhibitor. Biopolymers 1999;51:51-8
27. Kempf DJ, Marsh KC, Kumar G, et al. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 1997;41:654-60
28. Rathbun RC, Rossi DR. Low-dose ritonavir for protease inhibitor pharmacokinetic enhancement. Ann Pharmacother 2002;36:702-6
29. Petersen JL, Mcguire DK. Impaired glucose tolerance and impaired fasting glucose-a review of diagnosis, clinical implications and management. Diab Vasc Dis Res 2005;2:9-15
30. Tang JH, Sheffield JS, Grimes J, et al. Effect of protease inhibitor therapy on glucose intolerance in pregnancy. Obstet Gynecol 2006;107:1115-9
31. Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 2004;53:10-4
32. Montes ML, Pulido F, Barros C, et al. Lipid disorders in antiretroviral-naïve patients treated with topinavir/ritonavir-based HAART: frequency, characterization and risk factors. J Antimicrob Chemother 2005;55:800-4
33. Ergun-Longmire B, Lin-Su K, Dunn AM, et al. Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body composition in children and adolescents infected with human immunodeficiency virus. Endocr Pract 2006;12:514-21
34. Martinez E, Gatell JM. Metabolic abnormalities and body fat redistribution in HIV-1 infected patients: the lipodystrophy syndrome. Curr Opin Infect Dis 1999;12:13-9
35. Sundano I, Spieker LE, Noll F, et al. Cardiovascular disease in HIV infection. Am Heart J 2006;151:1147-55
36. Ogden R, Flexner C. Protease inhibitors in AIDS therapy. Volume 1. 1st edition. Marcel Dekker, AG, New York, 2001
37. Falcoz C, Jenkins JM, Bye C, et al. Pharmacokinetics of GW 433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol 2002;42:887-98
38. Vangeneugden T, Winters B, Bacheler L, et al. Impact of optimized background regimen on virological response to TMC 114 with low-dose ritonavir in POWER 1, 2, and 3, as measured by the phenotypic susceptibility score [abstract 31]. In: 15th International HIV Drug Resistance Workshop; 2006; Sitges, Spain Back
39. Miller JF, Andrews CW, Brieger M, et al. Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW 0385. Bioorg Med Chem Lett 2006;16:1788-94
40. Ford S, Reddy S, Anderson M, et al. Abstract 563, 12th Conference on Retroviruses and Opportunistic Infections, Boston, MA; 2005
41. Wu JJ, Stranix BR, Milot G, et al. PL-100, a next generation prorease inhibitor against drug-resistant HIV: in vitro & in vivo metabolism. 46th Annual ICAAC; 2006 September 27-30; San Francisco, USA
42. Miller JF, Furfine ES, Hanlon MH, et al. Novel arylsulfonamides possessing sub-picomolar HIV prorease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains. Bioorg Med Chem Lett 2004;14:959-63
43. Ali A, Reddy GSKK, Cao H, et al. Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands. J Med Chem 2006;49:7342-56
44. Ghosh AK, Sridhar PR, Leshchenko S, et al. Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance. J Med Chem 2006;49:5252-61
45. Kempf DJ, Isaacson JD, King MS, et al. 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 Virol 2001;75:7462-9
46. Friend J, Parkin N, Liegler T, et al. Isolated lopinavir resistance after virological rebound of a ritonavir/lopinavir-based regimen. AIDS 2004;18:1965-6
47. Conradie F, Sanne I, Venter W, Eton J. Failure of lopinavir-ritonavir (Kaletra)-containing regimen in an antiretroviral-naïve patient. AIDS 2004;18:1084-5
48. Marcelin AG, Cohen-Codar I, King MS, et al. Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients. Antimicrob Agents Chemother 2005;49:1720-6
49. Masquelier B, Breilh D, Neau D, et al. Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients. Antimicrob Agents Chemother 2002;46:2926-32
50. Mo H, King MS, King K, et al. Selection of resistance in protease inhibitor-experienced human immunodeficiency virus type 1-infected subjects failing lopinavir- and ritonavir-based therapy: mutation patterns and baseline correlates. J Virol 2005;79:3329-38
51. Rodes B, Toro C, Sheldon JA, et al. High rate of proV47A selection in HIV-2 patients failing lopinavir-based HAART. AIDS 2006;20:127-9
52. Yeung CM, Klein LL, Flentge CA, et al. Oximinoarylsulfonamides as potent HIV inhibitors. Bioorg Med Chem Lett 2005;15:2275-8
53. Randolph JT, Huang PP, Flosi WJ, et al. Synthesis, antiviral activity, and pharmacokinetic evaluation of P3 pyridylmethyl analogs of oximinoarylsulfonyl HIV-1 protease inhibitors. Bioorg Med Chem 2006;14:4035-46
54. Flosi WJ, Degoey DA, Grampovnik DJ, et al. Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV. Bioorg Med Chem 2006;14:6695-712
55. Poppe SM, Slade DE, Chong KT, et al. Antimicrob Agents Chemother 1997;41:1058-63
56. Baxter JD, Schapiro JM, Boucher CA, et al. Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virological response to the protease inhibitor tipranavir. J Virol 2006;80:10794-801
57. Colonno RJ, Hertogs K, Larder BA, et al. Abstracts of the 4th International Workshop on Drug Resistance and Treatment Strategies, Sitges, Spain, 12-16 June 2000. Antiviral Ther 2000;5(Suppl 3):7
58. Cheng Y, Zhang F, Rano TA, et al. Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains. Bioorg Med Chem Lett 2002;12:2419-22
59. Duffy JL, Rano TA, Kevin NJ, et al. HIV protease inhibitors with picomolar potency against PI-resistant HIV-1 by extension of the P3 substituent. Bioorg Med Chem Lett 2003;13:2569-72
60. Zhang F, Chapman KT, Schleif WA, et al. The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resisrant viral strains. Bioorg Med Chem Lett 2003;13:2573-6
61. Duffy JL, Kirk BA, Kevin NJ, et al. HIV protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent. Bioorg Med Chem Lett 2003;13:3323-6
62. Kevin NJ, Duffy JL, Kirk BA, et al. Novel HIV-1 protease inhibitors active against multiple PI-resistant viral strains: coadministration with indinavir. Bioorg Med Chem Lett 2003;13:4027-30
63. Kim RM, Rouse EA, Chapman KT, et al. P1′ oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1. Bioorg Med Chem Lett 2004;14:4651-4
64. Lu Z, Bohn J, Rano TA, et al. Orally bioavailable highly potent HIV protease inhibitors against PI-resistant virus. Bioorg Med Chem Lett 2005;15:5311-4
65. Mimoto T, Kato R, Takaku H, et al. Structure-activity relationship of small sized HIV protease inhibitors containing allophenyinorstatine. J Med Chem 1999;42:1789-802
66. Lu Z, Raghavan S, Bohn J, et al. Design and synthesis of highly potent HIV protease inhibitors with activity against resistant virus. Bioorg Med Chem Lett 2003;13:1821-4
67. Raghavan S, Lu Z, Beeson T, et al. Synthesis of novel HIV protease inhibitors (PI) with activity against PI-resistant virus. Bioorg Med Chem Lett 2007;17:5432-6
68. Hodge CN, Aldrich PE, Bacheler LT, et al. Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450. Chem Biol 1996;3:301-14
69. Sierra J, Nino S, Volkow P, et al. Abstracts of the 4th International Workshop on Drug Resistance and Treatment Strategies; 2000 June 12-16; Sitges, Spain. Antiviral Ther 2000;5(Suppl 3):6
70. Zhao C, Sham HL, Sun M, et al. Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains. Bioorg Med Chem Lett 2005;15:5499-503