Advances in non-peptidomimetic HIV protease inhibitors

Current Medicinal Chemistry

Volumn 21, Issue 17, 2014, Pages 1997-2011

  Pang, X ^a   Liu, Z ^a   Zhai, G ^a  

^a SHANDONG UNIVERSITY   (China)

Author keywords

Antiviral; Drug resistance; Human immunodeficiency virus; Non peptidomimetic inhibitors; Protease inhibitors

Indexed keywords

CARBORANE DERIVATIVE; CHROMONE DERIVATIVE; COUMARIN DERIVATIVE; CYCLIC UREA; DIHYDROPYRONE ANALOG; DRUG ANALOG; FULLERENE DERIVATIVE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; METALLACARBORANE; NON PEPTIDOMIMETIC HIV PROTEASE INHIBITOR; PYRONE DERIVATIVE; PYRROLIDINE DERIVATIVE; SMALL MOLECULE TRANSPORT AGENT; SULFANILAMIDE; UNCLASSIFIED DRUG; UREA DERIVATIVE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; ORGANOMETALLIC COMPOUND; SULFONAMIDE; UREA;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; CLINICAL PHARMACOLOGY; DRUG BIOAVAILABILITY; DRUG COST; DRUG DESIGN; DRUG STABILITY; DRUG STRUCTURE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; MEDICINAL CHEMISTRY; MOLECULAR WEIGHT; REVIEW; ANALOGS AND DERIVATIVES; CHEMISTRY; DRUG EFFECTS; ENZYMOLOGY; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS; METABOLISM; VIROLOGY;

DRUG DESIGN; DRUG RESISTANCE, VIRAL; FULLERENES; HIV; HIV INFECTIONS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HUMANS; ORGANOMETALLIC COMPOUNDS; PYRONES; PYRROLIDINES; SULFONAMIDES; UREA;

EID: 84899857989     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867321666140217115951     Document Type: Review

References (54)

1. Waterson, A. P. Acquired immune deficiency syndrome. Br. Med. J., 1983, 286, 743-746.
2. Michel Sidibé World AIDS Day Report|2013, http://www.unaids. org/en/( accessed June 10, 2013 )
3. Wensing, A.M; van Maarseveen, N.M.; Nijhuis, M. Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance. Antiviral. Res., 2010, 85, 59-74.
4. Kohl, N.E.; Emini, E.A.; Schleif, W.A.; Davis, L.J.; Heimbach, J.C.; Dixon, R.A.; Scolnick, E.M.; Sigal, I.S. Active human immunodeficiency virus protease is required for viral infectivity. Proc. Natl. Acad. Sci. U S A, 1988, 85, 4686-4690.
5. Martinez-Cajas, J.L.; Wainberg, M.A. Protease inhibitor resistance in HIV-infected patients: Molecular and clinical perspectives. Antiviral Res., 2007, 76 203-221.
6. De Clercq, E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int. J. Antimicrob. Agents, 2009, 33, 307-320.
7. Andany, N.; Loutfy, M.R. HIV protease inhibitors in pregnancy. Drugs, 2013, 73, 229-247.
8. Mitsuya, H.; Maeda, K.; Das, D.; Ghosh, A.K. Development of protease inhibitors and the fight with drug-resistant HIV-1 variants. Adv. Pharmacol., 2008, 56, 169-197.
9. Pokorná, J.; Rezacova, P.; Machala, L.; Konvalinka, J. Current and novel inhibitors of HIV protease. Viruses, 2009, 1, 1209-1239.
10. Worm, S.W.; Kamara, D.A.; Reiss, P.; Fontas, E.; De Wit, S.; EISadr, W.; dAeminio Monforte, A.; Law, M.; Phillips, A.; Ryom, L.; Dabis, F.; Weber, R.; Sabin, C.; Lundgren, J.D. Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke. J. Infect. Dis., 2012, 205, 535-539.
11. Dieter, S. How flexible is tipranavir in complex with the HIV-1 protease active site? Aids, 2004, 18, 579-580.
12. J. W. Heal; J. E. Jimenez-Roldan; S. A. Wells; R. B. Freedman; R. A. Römer Inhibition of HIV-1 protease: the rigidity perspective. Bioinformatics, 2012, 3, 350-357.
13. Thaisrivongs, S.; Strohbach, J.W. Structure-based discovery of tipranavir disodium (PNU-140690E): A potent, orally bioavailable, nonpeptidic HIV protease inhibitor. Biopolymer, 1999, 51, 51-58.
14. Croom, K.F.; Keam, S.J. Tipranavir: a ritonavir-boosted protease inhibitor. Drugs, 2005, 65, 1669-1677.
15. Wang, Y.; Liu, Z.; Brunzelle, J.S.; Kovari, J.A.; Dewdney, T.G.; Reiter, S.J.; Kovari, L.C. Higher barrier of darunavir and tipranavir resistance for HIV-1 protease. Biochem. Biophys. Res. Commun., 2011, 412, 737-742.
16. Sun, C.L.; Pang, R.F.; Zhang, H.; Yang, M. Design, synthesis, and biological evaluation of novel 4-hydroxypyrone derivatives as HIV-1 protease inhibitors. Bioorg. Med. Chem. Lett., 2005, 15, 3257-3262.
17. He, M.; Yang, N.; Sun, C.; Yao, X.; Yang, M. Modification and biological evaluation of novel 4-hydroxy-pyrone derivatives as non-peptidic HIV-1 protease inhibitors. Med. Chem. Res., 2011, 20, 200-209.
18. Stanchev, S.; Jensen, F.; Hinkov, A.; Atanasov, V.; Genova-Kalou, P.; Argirova, R.; Manolov, I. Synthesis and Inhibiting Activity of Some 4-Hydroxycoumarin Derivatives on HIV-1 Protease. ISRN Pharmaceutics, 2011, Volume 2011, Article ID 137637, 9 pages.
19. Ungwitayatorn, J.; Wiwat, C.; Samee, W.; Nunthanavanit, P.; Phosrithong, N. Synthesis, in vitro evaluation, and docking studies of novel chromone derivativesas HIV-1 protease inhibitor. J. Mol. Struct., 2011, 1001, 152-161.
20. Lam, P.Y.S.; Jadhav, P.K.; Eyermann, C.J.; Hodge, C.N.; Ru, Y.; Bacheler, L.T.; Meek, J.L.; Otto, M.J.; Rayner, M.M.; Wong, Y.N.; Chang, C.-H.; Weber, P.C.; Jackson, D.A.; Sharpe, T.R.; Erickson-Viitanen, S. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science, 1994, 263, 380-384.
21. Otto, M.J.; Reid, C.D.; Garber, S.; Lam, P.Y.S.; Scarnati, H.; Bacheler, L.T.; Rayner, M.M.; Winslow, D.L. In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor. Antimicrob. Agents Chemother., 1993, 37, 2606-2611.
22. Hodge, C.N.; Aldrich, P.E.; Bacheler, L.T.; Chang, C.H.; Eyermann, C.J.; Garber, S.; Grubb, M.; Jackson, D.A.; Jadhav, P.K; Korant, B.; Lam, P.Y.S.; Maurin, M.B.; Meek, J.L.; Otto, M.J.; Rayner, M.M.; Reid, C.; Sharpe, T.R.; Shum, L.; Winslow, D.L.; Erickson-Viitanen, S. 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, 301-314.
23. Gros, G.; Martinez, L.; Gimenez, A.S.; Adler, P.; Maurin, P.; Wolkowicz, R.; Falson, P.; Hasserodt, P. Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease. Bioorg. Med. Chem., 2013, 21, 5407-5413.
24. Ax, A.; Schaal, W.; Vrang, L.; Samuelsson, B.; Hallberga, A.; Karlén, A. Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2 to P1/P1. Bioorg. Med. Chem., 2005, 13, 755-764.
25. Kaldor S. W.; Appelt, K.; Fritz, J.; Hammond, M.; Crowell, T. A.; Baxter, A. J.; Hatch, S. D.; Wiskerchen, M. A.; Muesing, M. A. A systematic study of P1-P3 spanning sidechains for the inhibition of HIV-1 protease. Bioorg. Med. Chem. Lett. 1995, 5, 715-720.
26. Gold, H; Ax, A.; Vrang, L.; Samuelsson, B.; Karlén, A.; Hallberga, A.; Larheda, M. Fast and selective synthesis of novel cyclic sulfamide HIV-1 protease inhibitors under controlled microwave heating. Tetrahedron, 2006, 62, 4671-4675.
27. Ax, A.; Joshi, A.A.; Orrling, K.M.; Vrang, L.; Samuelsson, B.; Hallberg, A.; Karlén, A.; Larhed. M. Synthesis of a small library of non-symmetric cyclic sulfamide HIV-1 protease inhibitors. Tetrahedron, 2010, 66, 4049-4056.
28. Sijbesma, R.; Srdanov, G.; Wudl, F.; Castoro, J. A.; Wilkins, C.; Friedman, S. H.; DeCamp, D. L.; Kenyon, G. L. Synthesis of a Fullerene Derivative for the Inhibition of HIV Enzymes. J. Am. Chem. Soc., 1993, 115, 6510-6512.
29. Friedman H.S.; DeCamp, D.L.; Sijbesma, R.P.; Srdanov, G.; Wudl, F.; Kenyon, G. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J. Am. Chem. Soc. 1993, 115, 6506-6509.
30. Durdagi, S.; Supuran, C.T.; Amanda Strom, T.; Doostdar, N.; Kumar, M.K.; Barron, A.R.; Mavromoustakos, T.; Papadopoulos, M.G. In Silico drug screening approach for the design of magic bullets: a successful example with anti-HIV fullerene derivatized amino acids. J. Chem. Inf. Model., 2009, 49, 1139-1143.
31. Tanimoto, S.; Takahashi, S.; Toshima, K. Chemical methods for degradation of target proteins using designed light-activatable organic molecules. Chem. Commun., 2012, 48, 7659-7671.
32. Cígler, P.; Koíek, M.; ezáova, P.; Brynda, J.; Otwinowski, Z.; Pokorná, J.; Pleek, J.; Grüner, B.; Doleková-Mareová, L.; Máa, M.; Sedláek, J.; Bodem, J.; Kräusslich, H.G.; Král, V.; Konvalinka, J. From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease. Proc. Natl. Acad. Sci. U S A, 2005, 102, 15394-15399.
33. Koíek, M.; Cígler, P.; Lepík, M.; Fanfrlík, J.; Ezáova, P.; Brynda, J.; Pokorná, J.; Pleek, J.; Grüner, B.; Aková, K..G.; Václavíková, J.; Král, V.; Konvalinka, J. Inorganic polyhedral metallacarborane inhibitors of HIV protease: a new approach to overcoming antiviral resistance. J. Med. Chem., 2008, 51, 4839-4843.
34. ezáová, P.; Pokorná, J.; Brynda, J.; Koíek, M.; Cígler, P.; Lepík, M.; Fanfrlík, J.; ezá, J.; aková, K. G.; Sieglová, I.; Pleek, J.; ícha, V.; Grüner, B.; Oberwinkler, H.; Sedláek, J.; Kräusslich, H.G.; Hobza, P.; Král, V.; Konvalinka, J. Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes. J. Med. Chem., 2009, 52, 7132-7141.
35. Kubát, P.; Lang, K.; Cígler, P.; Koíek, M.; Matjíek, P.; Janda, P.; Zelinger, Z.; Procházka, K.; Král, V. Tetraphenylporphyrincobalt( III) bis(1,2-dicarbollide) conjugates: from the solution characteristics to inhibition of HIV protease. J. Phys. Chem. B, 2007, 111, 4539-4546.
36. Specker, E.; Böttcher, J.; Brass, S.; Heine, A.; Lilie, H.; Schoop, A.; Müller, G.; Griebenow, N.; Klebe, G. Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors: design, synthesis and crystal structure in complex with HIV protease. ChemMedChem, 2006, 1, 106-117.
37. Blum, A.; Böttcher, J.; Heine, A.; Klebe, G.; Diederich, W.E. Structure-Guided Design of C2-Symmetric HIV-1 Protease inhibitors based on a pyrrolidine scaffold. J. Med. Chem., 2008, 51, 2078-2087.
38. Böttcher, J.; Blum, A.; Heine, A.; Diederich W.E.; Klebe,G. Structural and Kinetic Analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. J. Mol. Biol., 2008, 383, 347-357.
39. Blum, A.; Böttcher, J.; Dörr, S.; Heine, A.; Klebe, G.; Diederich, W.E. Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors. J. Mol. Biol., 2011, 410, 745-755.
40. DeCamp, D.L.; Babé, L.M.; Craik, C.S. Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. Proc. Natl. Acad. Sci. U.S.A., 1990, 87, 6644-6648.
41. De Voss, J.J.; Sui, Z.H.; Decamp, D.L.; Salto, R.; Babé, L.M.; Craik, C.S.; Ortiz de Montellano, P.R. Haloperidol-based irreversible inhibitors of the HIV-1 and HIV-2 proteases. J. Med. Chem., 1994, 37, 665-673.
42. Humber, D.C.; Cammack, N.; Coates, J.A.; Cobley, K.N.; Orr, D.C.; Storer, R.; Weingarten, G.G.; Weir, M.P. Penicillin derived C2-symmetric dimers as novel inhibitors of HIV-1 proteinase. J. Med. Chem., 1992, 36, 3080-3081.
43. Humber, D.C.; Bamford, M.J.; Bethell, R.C.; Cammack, N.; Cobley, K.; Evans, D.N.; Gray, N.M.; Hann, M.M.; Orr, D.C.; Saunders, J.; Shenoy, B.V.; Storer, R.; Weingarten, G.G.; Wyatt, P.G. A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: synthesis, mode of interaction, and structureactivity relationships. J. Med. Chem., 1993, 36, 3120-3128.
44. Potts, B. C. M.; Faulkner, D. J.; Chan, J. A.; Simolike, G. C.; Offen, P.; Hemling, M. E.; Francis, T. A. Didemnaketals A and B, HIV-1 protease inhibitors from the ascidian Didemnum sp. J. Am. Chem. Soc., 1991, 113, 6321-6322.
45. Chen, T.S.; Doss, G.A.; Hsu, A.; Hsu, A.; Lingham, R.B.; White, R.F.; Monaghan, R.L.; Microbial transformation of L-696, 474, a novel cytochalasin as an inhibitor of HIV-1 protease. J. Nat. Prod., 1993, 56, 755-761.
46. Cushman, M.; Golebiewski, W.M.; Pommier, Y.; Mazunder, A.; Reymen, D.; De Clercq, E.; Grahm, L.; Rice, W.G. Cosalane analogs with enhanced potencies as inhibitors of HIV-1 protease and integrase. J. Med. Chem., 1995, 38, 443-452.
47. Ding, Y.-L.; Chamakura V.N.S. Vara Prasad; Smith, K. L.; Eugene Chang, Jian Hong, J.; Yao, N.-H. Synthesis of Tipranavir Analogues as Non-Peptidic HIV Protease Inhibitors. Lett. Org. Chem., 2009, 6, 130-133.
48. Schobert, R.; Stehle, R.; Walter, H. Tipranavir analogous 3-sulfonylanilido-tetronic acids: new synthesis and structuredependent anti-HIV activity. Tetrahedron, 2008, 64, 9401-9407.
49. Wollmann, J.; Baumert, C.; Erlenkamp, G.; Sippl, W.; Hilgeroth, A. Novel Insight into Inhibitor Binding of Highly Symmetric HIV-1 Protease. ChemBioChem, 2008, 9, 874-878.
50. Wei, Y.; Ma, C.-M.; Hattori, M. Synthesis of dammarane-type triterpene derivatives and their ability to inhibit HIV and HCV proteases. Bioorg. & Med. Chem., 2009, 17, 3003-3010.
51. Liu, W.; Tang, W.-T.; Guo, Y.; Sun, B.; Zhu, H.-M.; Xiao, Y.-Y.; Dong, D.-D.; Yang, C. Synthesis, characterization and bioactivity determination of ferrocenyl urea derivatives, Appl. Organometal. Chem., 2012, 26, 189-193.
52. Flausino Jr., O.A.; Dufau, L.; Regasini, L.O.; Petrônio, M.S.; Silva, D.H.S.; Rose, T.; Bolzani, V.S.; Reboud-Ravaux, M. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization. ChemMedChem, 2012, 19, 4534-4540.
53. Tiefenbrunn, T.; Forli, S.; Baksh, M.M.; Chang, M.W.; Happer, M.; Lin, Y.C.; Perryman, A.L.; Rhee, J.K.; Torbett, B.E.; Olson, A.J.; Elder, J.H.; Finn, M.G.; Stout, C.D. Small molecule regulation of protein conformation by binding in the flap of HIV protease. ACS Chem. Biol., 2013, 8, 1223-1231.
54. Tiefenbrunn, T.; Forli, S.; Baksh, M.M.; Chang, M.W.; Happer, M.; Lin, Y.C.; Perryman, A.L.; Rhee, J.K.; Torbett, B.E.; Olson, A.J.; Elder, J.H.; Finn, M.G.; Stout, C.D. Small molecule regulation of protein conformation by binding in the flap of HIV protease. ACS Chem. Biol., 2013, 8, 1223-1231.