Developments of indoles as anti-HIV-1 inhibitors

Current Pharmaceutical Design

Volumn 15, Issue 18, 2009, Pages 2120-2148

  Xu, Hui ^a   Lv, Min ^a  

^a NORTHWEST A F UNIVERSITY   (China)

Author keywords

Acquired immunodeficiency syndrome; Human immunodeficiency virus; Indole; Inhibitor; Structure activity relationship; Synthesis

Indexed keywords

2 INDOLE3 YLDIPYRIDODIAZEPINONE DERIVATIVE; 4,5 DIFLUORO INDOLE DERIVATIVE; 5 CHLORO 4 FLUORO INDOLE DERIVATIVE; 6 AZAINDOL 3 YL DERIVATIVE; AZATHIOPRINE; INDOLE 2 CARBOXAMIDE DERIVATIVE; INDOLE 3 SULFONAMIDE DERIVATIVE; INDOLE DERIVATIVE; INDOYL SULFONE DERIVATIVE; L 737126; NEVIRAPINE; OXINDOLE DERIVATIVE; PIPERAZINE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; CONCENTRATION RESPONSE; CYTOPATHOGENIC EFFECT; CYTOTOXICITY; DRUG SYNTHESIS; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; VIRUS REPLICATION;

ANTI-HIV AGENTS; CATALYSIS; CELL SURVIVAL; HIV-1; HUMANS; INDOLES; MOLECULAR STRUCTURE; RECEPTORS, CCR5; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68449083305     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209788489168     Document Type: Review

References (90)

1. UNAIDS, Report on the global HIV/AIDS epidemic in 2007.
2. UNAIDS, Report on the global HIV/AIDS epidemic in 2002.
3. De Clercq E. New developments in anti-HIV chemotherapy. Biochim Biophy Acta 2002; 1587: 258-75.
4. Ho DD, Bieniasz PD. HIV-1 at 25. Cell 2008; 133: 561-5.
5. Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, Griffin JL. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 1990; 322: 1098-105.
6. Lambert JS, Seidlin M, Reichman RC, Plank CS, Laverty M, Morse GD, et al. 2', 3'- Dideoxyinosine (ddI) in patients with acquired immunodeficiency syndrome or AIDS-related complex. a phase 1 trial. N Engl J Med 1990; 322: 1333-40.
7. Yerly S, Kaiser L, Race E, Bru JP, Clavel F, Perrin L. Transmission of antiretroviral-drug-resistant HIV-1 variants. Lancet 1999; 354: 729-33.
8. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: Risk factors for virologic failure and adverse drug reactions. Ann Intern Med 1999; 13: 81-7.
9. Johnston MI, Hoth DF. Present status and future prospects for HIV therapies. Science 1993; 260: 1286-93.
10. Bourinbaiar AS. HIV drug design. Curr Pharm Des 2006; 12(16): 1941-2.
11. Agrawal L, Lu X, Jin Q, Alkhatib G. Anti-HIV therapy: Current and future directions. Curr Pharm Des 2006; 12(16): 2031-55.
12. Campiani G, Ramunno A, Maga G, Nacci V, Fattorusso C, Catalanotti B, et al. Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: Past, present, and future perspectives. Curr Pharm Des 2002; 8(8): 615-57.
13. Sluis-Cremer N, Ross T. HIV-1 reverse transcriptase inhibitors: Drug resistance and drug development. Curr Pharm Des 2006; 12(15): 1809-10.
14. Martins S, Ramos MJ, Fernandes PA. The current status of the NNRTI family of antiretrovirals used in the HAART regime against HIV infection. Curr Med Chem 2008; 15(11): 1083-95.
15. Deng J, Dayam R, Al-Mawsawi LQ, Neamati N. Design of second generation HIV-1 integrase inhibitors. Curr Pharm Des 2007; 13(2): 129-41.
16. Klumpp K, Mizadegan T. Recent progress in the design of small molecule inhibitors of HIV RNase H. Curr Pharm Des 2006; 12(15): 1909-22.
17. Somei M, Yamada F. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat Prod Rep 2003; 20: 216-42.
18. Terzioglu N, Karah N, Gursoy A, Pannecouque C, Leysen P, Paeshuyse J, et al. Synthesis and primary antiviral activity evaluation of 3-hydrazono-5-nitro-2-indolinone derivatives. Arkivoc 2006; i: 109-18.
19. Van Maarseveen JH, Hermkens PHH, De Clercq E, Balzarini J, Scheeren HW, Kruse CG. Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines. J Med Chem 1992; 35: 3223-30.
20. Williams JD, Drach JC, Townsend LB. Synthesis and antiviral activity of some 2-substituted 3-formyl- and 3-cyano-5,6-dichloroindole nucleosides. Nucleosides Nucleotides Nucleic Acids 2005; 24: 1613-26.
21. Chen JJ, Wei Y, Williams JD, Drach JC, Townsend LB. Design, synthesis, and antiviral evaluation of some polyhalogenated indole C-nucleosides. Nucleosides Nucleotides Nucleic Acids 2005; 24: 1417-37.
22. Williams JD, Chen JJ, Drach JC, Townsend LB. Synthesis and antiviral activity of 3-formyl- and 3-cyano-2,5,6-trichloroindole nucleoside derivatives. J Med Chem 2004; 47: 5766-72.
23. Chen JJ, Wei Y, Drach JC, Townsend LB. Synthesis and antiviral evaluation of trisubstituted indole N-nucleosides as analogues of 2,5,6-trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB). J Med Chem 2000; 43: 2449-56.
24. Williams JD, Chen JJ, Drach JC, Townsend LB. Design, synthesis, and antiviral activity of certain 3-substituted 2,5,6-trichloroindole nucleosides. J Med Chem 2004; 47: 5753-65.
25. Williams JD, Ptak RG, Drach JC, Townsend LB. Synthesis, antiviral activity, and mode of action of some 3-substituted 2,5,6-trichloroindole 2'- and 5'-deoxyribonucleosides. J Med Chem 2004; 47: 5773-82.
26. Slater MJ, Baxter R, Bonser RW, Cockerill S, Gohil K, Parry N, et al. Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication. Bioorg Med Chem Lett 2001; 11: 1993-5.
27. Moreau P, Anizon F, Sancelme M, Prudhomme M, Bailly C, Carrasco C, et al. Synthesis and biological evaluation of indolocarbazoles, analogues of rebeccamycin, modified at the imide heterocycle. J Med Chem 1998; 41: 1631-40.
28. De Martino G, Edler MC, La Regina G, Coluccia A, Barbera MC, Barrow D, et al. New arylthioindoles: Potent inhibitors of tubulin polymerization. 2. structure-activity relationships and molecular modeling studies. J Med Chem 2006; 49: 947-54.
29. De Martino G, La Regina G, Coluccia A, Edler MC, Barbera MC, Brancale A, et al. Arylthioindoles, potent inhibitors of tubulin polymerization. J Med Chem 2004; 47: 6120-3.
30. Abdel-Rahman AAH, El-Sayed WA, Abdel-Bary HM, Abdel-Megied AES, Morcy EMI. Amino acid derivatives, VIII [1]: Synthesis and antimicrobial evaluation of amino acid esters bearing an indole side chain. Monatsh Chem 2008; 139: 1095-101.
31. Trani G, Baddeley SM, Briggs MA, Chuang TT, Deeks NJ, Johnson CN, et al. Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists. Bioorg Med Chem Lett 2008; 18: 5698-700.
32. Ghosh AK, Gong G, Grum-Tokars V, Mulhearn DC, Baker SC, Coughlin M, et al. Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett 2008; 18: 5684-8.
33. Karah N, Gursoy A, Kandemirli F, Shvets N, Kaynak FB, Ozbey S, et al. Synthesis and structure-antituberculosis activity relationship of 1 H-indole-2,3-dione derivatives. Bioorg Med Chem 2007; 15: 5888-904.
34. Guzel O, Karali N, Salman A. Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives. Bioorg Med Chem 2008; 16: 8976-87.
35. Silvestri R, Artico M. Indolyl aryl sulfones (IASs): Development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants. Curr Pharm Des 2005; 11(29): 3779-806.
36. Romero DL, Morge RA, Genin MJ, Biles C, Busso M, Resnick L, et al. Bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationships of novel substituted indole analogs and the identification of 1-[(5-methanesulfonamido-1H-indol-2-yl) carbonyl]-4-[3-[(1-methylethyl) aminopyridinylpiperazinemonomethanesulfonate (U-90152S), a second-generation clinical candidate. J Med Chem 1993; 36: 1505-8.
37. Romero DL, Morge RA, Biles C, Berrios-Pena N, May PD, Palmer JR, et al. Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors. J Med Chem 1994; 37: 999-1014.
38. Font M, Monge A, Cuartero A, Elorriaga A, Martinez-Irujo JJ, Alberdi E, et al. Indoles and pyridazino[4,5-b]indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase. Eur J Med Chem 1995; 30: 963-71.
39. Williams TM, Ciccarone TM, MacTough SC, Rooney CS, Balani SK, Condra JH, et al. 5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: A novel non-nucleoside inhibitor of HIV-1 reverse transcriptase. J Med Chem 1993; 36: 1291-4.
40. Young SD, Amblard MC, Britcher SF, Grey VE, Tran LO, Lumma WC, et al. 2-Heterocyclic indole-3-sulfones as inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1995; 5: 491-6.
41. Romero DL, Morge RA, Genin MJ, Biles C, Busso M, Resnick L, et al. Bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationships of novel substituted indole analogs and the identification of 1-[(5-methanesulfonamido-1H-indol-2-yl) carbonyl]-4-[3-[(1- methylethyl)amino]pyridinyl]pipera- zinemonomethanesulfonate (U-90152S), a second-generation clinical candidate. J Med Chem 1993; 36: 1505-8.
42. Islam I, Hinshaw RR, Chong KT, Kato A, Borchardt RT, Fisher JF. Synthesis and antiviral activity of [2-4-[3-[(1-methylethyl)-amino]-2-pyridyl]-1-piperazinyl]carbonyl]-1 H-indol-5-yl (BHAP) acylsphingosine HIV reverse transcriptase inhibitors. Bioorg Chem 1995; 23: 499-511.
43. Artico M, Silvestri R, Massa S, Loi AG, Corrias S, Piras G, et al. 2-Sulfonyl-4-chloroanilino moiety: A potent pharmacophore for the anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones. J Med Chem 1996; 39: 522-30.
44. Slade DE, Kopta LA, Poppe SM, Poel TJ, Newport SW, Rank KB, et al. (Alkylamino)piperidine BHAP analogs are potent broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of HIV-1 and select for drug resistant variants of HIV-1IIIB with reduced replication phenotypes. J Virol 1996; 3698-705.
45. Romero DL, Olmsted RA, Poel TJ, Morge RA, Biles C, Keiser BJ, et al. Targeting delavirdine/atevirdine resistant HIV-1: Identification of (alkylamino)piperidine-containing bis(heteroaryl)piperazines as broad spectrum HIV-1 reverse transcriptase inhibitors. J Med Chem 1996; 39: 3769-89.
46. Genin MJ, Poel TJ, Yagi Y, Biles C, Althaus I, Keiser BJ, et al. Synthesis and bioactivity of novel bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: Structure-activity relationships and increased metabolic stability of novel substituted pyridine analogs. J Med Chem 1996; 39: 5267-75.
47. Proudfoot JR, Hargrave KD, Kapadia SR, Patel UR, Grozinger KG, McNeil DW, et al. Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 4. 2-Substituted dipyridodiazepinones are potent inhibitors of both wild type and cysteine-181 HIV reverse transcriptase enzymes. J Med Chem 1995; 38: 4830-8.
48. Kelly TA, McNeil DW, Rose JM, David E, Shih CK, Grob PM. Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 6. 2-indol-3-yl- and 2-azaindol-3-yl-dipyridodiazepinones. J Med Chem 1997; 40: 2430-3.
49. Giannotti D, Viti G, Nannicini R, Pestellini V, Bellarosa D. Synthesis and anti-HIV-1 activity of new thiadiazepindioxides. Bioorg Med Chem Lett 1995; 5: 1461-6.
50. Hargrave KD, Proudfoot JR, Grozinger KG, Cullen E, Kapadia SR, Patel UR, et al. Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones. J Med Chem 1991; 34: 2231-41.
51. Kukla MJ, Breslin HJ, Pauwels R, Fedde CL, Miranda M, Scott MK, et al. Synthesis and HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk]1,4] benzodiazepine-2(1H)-one (TIBO) derivatives. J Med Chem 1991; 34: 746-51.
52. Terret NK, Bojanic D, Merson JR, Stephenson PT. Imidazo-[2',3':6,5] dipyrido[3,2-b:2',3N -e]-1,4-diazepines: non-nucleoside HIV-1 reverse transcriptase inhibitors with greater enzyme affinity than nevirapine. Bioorg Med Chem Lett 1992; 2: 1745-50.
53. Silvestri R, Artico M, Bruno B, Massa S, Novellino E, Greco G, et al. Synthesis and biological evaluation of 5H-indolo[3,2- b][1,5]-benzothiazepine derivatives, designed as conformationally constrained analogues of the human immunodeficiency virus type 1 reverse transcriptase inhibitor L-737,126. Antiviral Chem Chemother 1998; 9: 139-48.
54. Merino I, Monge A, Font M, Martinez de Irujo JJ, Alberdi E, Santiago E, Prieto I, et al. Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles. Il Farmaco 1999; 54: 255-64.
55. Silvestri R, De Martino G, La Regina G, Artico M, Massa S, Vargiu L, et al. Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: Synthesis and SAR studies. J Med Chem 2003; 46: 2482-93.
56. Silvestri R, Artico M, De Martino G, La Regina G, Loddo R, La Colla M, et al. Simple, short peptide derivatives of a sulfonylin-dolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations. J Med Chem 2004; 47: 3892-6.
57. Serradji N, Bensaid O, Martin M, Kan E, Dereuddre-Bosquet N, Redeuilh C, et al. Structure-activity relationships in platelet-activating factor (PAF). 10. from PAF antagonism to inhibition of HIV-1 replication. J Med Chem 2000; 43: 2149-54.
58. Sallem W, Serradji N, Dereuddre-Bosquet N, Dive G, Clayette P, Heymans F. Structure-activity relationships in platelet-activating factor. Part 14: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 activity. Bioorg Med Chem 2006; 14: 7999-8013.
59. Jiang T, Kuhen KL, Wolff K, Yin H, Bieza K, Caldwell J, et al. Design, synthesis and biological evaluations of novel oxindoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. Part 1. Bioorg Med Chem Lett 2006; 16: 2105-8.
60. Jiang T, Kuhen KL, Wolff K, Yin H, Bieza K, Caldwell J, et al. Design, synthesis and biological evaluations of novel oxindoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. Part 2. Bioorg Med Chem Lett 2006; 16: 2109-12.
61. Ragno R, Artico M, De Martino G, La regina G, Coluccia A, Di Pasquali A, et al. Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl) carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives. J Med Chem 2005; 48: 213-23.
62. Ragno R, Coluccia A, La Regina G, De Martino G, Piscitelli F, Lavecchia A, et al. Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. novel derivatives of the indole-2-carboxamide. J Med Chem 2006; 49: 3172-84.
63. Artico M, Silvestri R, Massa S, Loi AG, Corrias S, Piras G, et al. 2-Sulfonyl-4-chloroanilino moiety: A potent pharmacophore for the anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones. J Med Chem 1996; 39: 522-30.
64. Artico M, Silvestri R, Pagnozzi E, Bruno B, Novellino E, Greco G, et al. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations. J Med Chem 2000; 43: 1886-91.
65. De Martino G, La Regina G, Ragno R, Coluccia A, Bergamim A, Ciaprini C, et al. Indolyl aryl sulfones (IASs) as HIV-1 non-nucleoside reverse transcriptase inhibitors: Synthesis. Biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide. Antiviral Chem Chemother 2006; 57: 59-77.
66. La Regina G, Coluccia A, Piscitelli F, Bergamini A, Sinistro A, Cavazza A, et al. Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: Role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity. J Med Chem 2007; 50: 5034-8.
67. Zhao Z, Wolkenberg SE, Lu M, Munshi V, Moyer G, Feng M, et al. Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). Bioorg Med Chem Lett 2008; 18: 554-9.
68. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996; 272: 872-7.
69. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, et al. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996; 85: 1135-48.
70. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996; 381: 661-6.
71. Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, et al. CC CKR5: A RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage tropic HIV-1. Science 1996; 272: 1955-8.
72. Kim D, Wang L, Caldwell CG, Chen P, Finke PE, Oates B, et al. Discovery of human CCR5 antagonists containing hydantoins for the treatment of HIV-1 infection. Bioorg Med Chem Lett 2001; 11: 3099-3102.
73. Reich SH, Melnick M, Pino MJ, Fuhry MAM, Trippe AJ, Appelt K, et al. Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease: Secondary amide series. J Med Chem 1996; 39: 2781-94.
74. Melnick M, Reich SH, Lewis KK, Mitchell LJ, Nguyen D, Trippe AJ, et al. Bis tertiary amide inhibitors of the HIV-1 protease generated via protein structure-based iterative design. J Med Chem 1996; 39: 2795-2811.
75. Santo RD, Costi R, Artico M, Massa S, Ragno R, Marshall GR, et al. Design, synthesis and QSAR studies on N-aryl heteroaryliso-propanolamines, a new class of non-peptidic HIV-1 protease inhibitors. Bioorg Med Chem 2002; 10: 2511-26.
76. Palella FJJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N Engl J Med 1998; 338: 853-60.
77. Pommier Y, Neamati N. Inhibitors of human immunodeficiency virus integrase. Adv Virus Res 1999; 52: 427-58.
78. Pais GCG, Zhang X, Marchand C, Neamati N, Cowansage K, Svarovskaia ES, et al. Structure activity of 3-aryl-1,3-diketo-containing compounds as HIV-1 integrase inhibitors. J Med Chem 2002; 45: 3184-94.
79. Wai JS, Egbertson MS, Payne LS, Fisher TE, Embrey MW, Tran LO, et al. 4-Aryl-2,4-dioxobutanoic acid inhibitors of HIV-1 integrase and viral replication in cells. J Med Chem 2000; 43: 4923-6.
80. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000; 287: 646-50.
81. Pais GCG, Burke TR. Novel aryl diketo-containing inhibitors of HIV-1 integrase. Drugs Future 2002; 27: 1101-11.
82. Neamati N. Patented small molecules inhibitors of HIV-1 integrase: A ten-year saga. Exp Opin Ther Pat 2002; 12: 709-24.
83. Sechi M, Derudas M, Dallocchio R, Dessi A, Bacchi A, Sannia L, et al. Design and synthesis of novel indole β-diketo acid derivatives as HIV-1 integrase inhibitors. J Med Chem 2004; 47: 5298-310.
84. Barreca ML, Ferro S, Rao A, De Luca L, Zappala M, Monforte AM, et al. Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors. J Med Chem 2005; 48: 7084-8.
85. Zhuang L, Wai JS, Embrey MW, Fisher TE, Egbertson MS, Payne LS, et al. Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J Med Chem 2003; 46: 453-6.
86. Ferro S, Barreca ML, De Luca L, Rao A, Monforte AM, Debyser Z, et al.New 4-[(1-benzyl-1H-indol-3-yl)carbonyl]-3-hydroxyfuran- 2(5H)-ones, β-diketo acid analogs as HIV-1 integrase inhibitors. Arch Pharm Chem Life Sci 2007; 340: 292-8.
87. De Luca L, Barreca ML, Ferro S, Iraci N, Michiels M, Christ F, et al. A refined pharmacophore model for HIV-1 integrase inhibitors: optimization of potency in the 1H-benzylindole series. Bioorg Med Chem Lett 2008; 18: 2891-5.
88. Cossarizza A. Apoptosis and HIV infection: About molecules and genes. Curr Pharm Des 2008; 14(3): 237-44.
89. Grande F, Garofalo A, Neamati N. Small molecules anti-HIV therapeutics targeting CXCR4. Curr Pharm Des 2008; 14(4): 385-404.
90. Xie L, Guo HF, Lu H, Zhuang XM, Zhang AM, Wu G, et al. Development and preclinical studies of broad-spectrum anti-HIV agent (3'R,4'R)-3-cyanomethyl-4-methyl- 3',4'-di-O-(S)-camphanoyl-(+)- cis-khellactone (3-cyanomethyl-4-methyl-DCK). J Med Chem 2008 Dec 25; 51(24): 7689-96.