Indolyl aryl sulfones (IASs): Development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants

Current Pharmaceutical Design

Volumn 11, Issue 29, 2005, Pages 3779-3806

  Silvestri, Romano ^a   Artico, Marino ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

AIDS; HIV 1; Indolol aryl sulfones; NNRTI; Reverse transcriptase

Indexed keywords

2 HYDROXYETHYLCARBOXAMIDE; 2 HYDROXYETHYLCARBOXYHYDRAZIDE; 5 BROMO 3 [(3,5 DIMETHYLPHENYL)SULFONYL]INDOLE 2 CARBOXAMIDE; 5 CHLORO 3 (BENZENESULFONYL)INDOLE 2 CARBOXAMIDE; 5 CHLORO 3 [(3,5 DIMETHYLPHENYL)SULFONYL]INDOLE 2 CARBOXAMIDE; ALANINE; AMIDE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DELAVIRDINE; EFAVIRENZ; ETHYL 1 [(2 AMINO 5 CHLOROPHENYL)SULFONYL] 1H INDOLE 2 CARBOXYLATE; ETHYL 1 BENZENESULFONYL 1H INDOLE 3 CARBOXAMIDE; ETHYL 1 BENZENESULFONYL 1H INDOLE 3 CARBOXYLATE; GLYCINE; HALOGEN; HYDRAZIDE DERIVATIVE; INDOLE DERIVATIVE; L 737126; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NEVIRAPINE; NITRO DERIVATIVE; NSC 665527; NSC 667952; PEPTIDE DERIVATIVE; PYRROLOBENZOTHIADIAZEPINE; RD4 2217; RNA DIRECTED DNA POLYMERASE INHIBITOR; SULFONE DERIVATIVE; TROVIRDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; CLINICAL STUDY; CYTOTOXICITY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; VIRUS MUTANT; VIRUS RESISTANCE; VIRUS STRAIN; WILD TYPE;

DRUG DESIGN; DRUG RESISTANCE, VIRAL; HIV-1; HUMANS; INDOLES; MUTATION; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 27744462731     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161205774580624     Document Type: Review

References (111)

1. UNAIDS, Report on the global HIV/AIDS epidemic in 2002.
2. Mellors J, Rinaldo C, Gupta P, White R, Todd J, Kingsley L. Prognosis of HIV-1 infection predicted by the quantity of virus in plasma. Science 1996; 272: 1167-70.
3. De Clercq E. Targets and strategies for the antiviral chemotherapy of AIDS. Trends Pharmacol Sci 1990; 11: 1298-05.
4. De Clercq E. Toward Improved Anti-HIV Chemotherapy: Therapeutic Strategies for Intervention with HIV Infections. J Med Chem 1995; 38: 2491-17.
5. Neamati N, Sunder S, Ponimier Y. Design and discovery of HIV-1 integrase inhibitors. Drug Disc Today 1997; 2: 261-72.
6. De Clercq E. New perspectives for the treatment of HIV infections. Coll Czech Chem Com 1998; 63: 449-79.
7. Jung M, Lee S, Kim H. Recent studies on natural products as anti-HIV agents. Curr Med Chem 2000; 7: 649-61.
8. De Clercq E. Highlights in the development of new antiviral agents. Mini-Review in Med Chem 2002; 2:163-75.
9. Tantillo C, Ding J, Jacobo-Molina A, Nanni RG, Boyer PL, Hughes SH, et al. Locations of anti-AIDS drug binding sites and resistant mutations in the three dimensional structure of HIV-1 reverse trancriptase. J Mol Biol 1994; 243: 369-87.
10. Spence RA, Kati WM, Anderson KS, Johnson KA, Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 1995; 267: 988-93.
11. Barrish JC, Zahler R. In: Annual Progress in Med. Chem., 28, Chapter 14, Antiviral Agents, Academic Press Inc. 1993.
12. Vandamme A-M, Van Vaerenbergh K, De Clercq E. Anti-human immunodeficiency virus drug combination strategies. Antiviral Chem Chemoth 1998; 9: 187-03.
13. De Clercq E, Balzarini J. Knocking out human immunodeficiency virus through non-nucleoside reverse transcriptase inhibitors used as single agents or in combinations: a paradigm for the cure of AIDS? Farmaco 1995; 50: 735-47.
14. King RW, Klabe RM, Reid CD, Erickson-Viitanen SK. Potency of non nucleoside reverse transcriptase inhibitors (NNRTIs) used in combination with other human immunodeficiency virus NNRTIs, NRTIs, or protease inhibitors. Antimicrob Agents Chemother 2002; 46: 1640-46.
15. Artico M. Non-nucleoside anti-HIV-1 reverse transcriptase inhibitors (NNRTIs): a chemical survey from lead compounds to selected drugs for clinical trials. Farmaco 1996; 51: 305-31.
16. Turcker TJ, Lumma WC, Culberson JC. Development of nonnucleoside reverse transcriptase inhibitors. Methods Enzymol 1996; 275: 440-72.
17. De Clercq E. The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV- 1 infection. Antiviral Res 1998, 38: 153-79.
18. Romero, DL, Busso, M, Tan C-K, Reusser F, Palmer JR, Poppe SM, et al. Non-nucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication. Proc Nad Acad Sci USA 1991; 88: 8806-10.
19. Pedersen OS, Pedersen EB. Non-nucleoside reverse trasncriptase inhibitors: the NNRTI boom. Antivir Chem Chemother 1999; 10: 285-14.
20. Hajós G, Riedl Z, Molnár J, Szabó D. Nonnucleoside reverse transcriptase inhibitors. Drugs Fut 2000; 25: 47-62.
21. 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 Design 2002; 8: 615-57.
22. Hargrave KD, Proudfoot JR, Grozinger KG, Culle E, Kapadia SR, Patel UR, et al. Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Triciclyc pyridobenzo- and dipiridodiazepinones. J Med Chem 1991; 34:2231-41.
23. Klunder JM, Hargrave KD, West M, Cullen E, Pal K, Behnke M, et al. Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2, Tricyclic pyridoxazepinones and dibenzoxazepinones. J Med Chem 1992; 35: 1887-97.
24. Proudfoot JR, Patel UR, Kapadia SR, Hargrave KD. Novel non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 3. Dipyrido[2, 3-b:[2′, 3′-c]diazepinones. J Med Chem 1995; 38: 1406-10.
25. Proudfoot JR, Hargrave KD, Kapadia SR, Patel UR, Grozinger KG, McNeil DW, et al. Novel don-nucleoside inhibitor of human immunodeficiency vinis type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepirtones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcripase enzymes. J Med Chem 19,95; 38: 4830-38.
26. Kelly TA, Proudfoot JR, McNeil DW, Patel UR, David E, Hargrave KD, et al. Novel non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 5. 4-Substituted and 2, 4-disubstituted analogs of nevirapine. J Med Chem 1995; 38: 4839-47.
27. Kelly TA, McNeil DW, Rose JM, David E, Shih, C-K, Grob PM. Novel non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 6. Indolyl-3-yl and 2-azaindol-3-yl-dipyridodiazepinones. J Med Chem 1997; 40: 2430-33.
28. Klunder JM, Hoermann M, Cywin CL, David E, Brirkwood JR, Schawartz R, et al. Novel non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 7. 8-Arylethyidipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes. J Med Chem 1998; 41: 2960-71.
29. Kukla MJ, Breslin HJ, Pauwels R, Fedde CL, Miranda M, Scott MK, et al. Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,jk],[1-4]benzodiazepin-2(IH)one (TIBO) derivatives. J Med Chem 1991; 34: 746-51.
30. Kukla MJ, Breslin W, Diamond CJ, Grous PP, Ho CY, Miranda R et al. Synthesis and anti-HIV-1 activity of 4, 5, 6, 7-tetrahydro-5-methylimidazo[4,5,I-jk][1,4]benzodiazepin-2(IH)one (TIBO) derivatives. 2. J Med Chem 199 1; 34: 3187-97.
31. Breslin HJ, Kukla MJ, Ludovici DW, Mohrbacher R, Ho, CY, Miranda R, et al. Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jkl[1,4]benzodiampin-2(IH)one (TIBO) derivatives. 3. J Med Chem 1995; 38: 771-93.
32. Ho W, Kukla MJ, Breslin HJ, Ludovici DW, Grous PP, Diamond CJ, et al. Synthesis and anti-HIV- 1 activity of 4,5,6,7-tetrahydro-5-methytimidazo[4,5,1-jk][1,4]benzodiazepin-2(IH)one (TIBO) derivatives. 4. J Med Chem 1995; 38: 794-02.
33. Aligren C, Backro K, Bell FW, Cantrell AS, Clemens M, Colacino JM, et al. The PETT series, a new class of potent nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1995; 39: 1239-35.
34. Bell FW, Cantrell AS, Högberg M, Jaskunas SR, Johansson SG, Jordan CL, et al. Phenylethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs. J Med Chem 1995; 38: 4929-36.
35. Cantrell AS, Engelhardt JA, Högberg M, Jaskunas SR, Johansson SG, Jordan CL, et al. Phenylethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs. J Med Chem 1996; 39: 4261-74.
36. Vig R, Mao C, Velikatachalam TK, Tuel-Ahlgren L, Sudbeck EA, Uckun FM. Rational design and synthesis of phenylethyl-5-bromopyridyl thiourea derivatives as a potent non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem 1998; 6:1789-97.
37. Mao C, Vig R, Venkatachalam TK, Sudbeck EA, Uckun FM. Structure-based design of N-[2-(I-piperidylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinyt ethyl]N′-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV- 1 reverse transcriptase. Bioorg Med Chem Lett 1998; 8: 2213-18.
38. Chen M, Sudbeck EA, Venkatachalam TK, Ukcun FM. Rational design of N-[2-(2,5-Dimethoxyphenylethyl)]-N′-[2-(5-bromopyridyl)-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus. Bioorg Med Chem Lett 1999; 9: 1593-98.
39. Uckun FM, Pendergrass S, Mahere D, Zhu D, Tuel-Ahlgren L, Mao C, et al. N-[2-(2-thiophene)ethyl]-N′-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resitant and multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999; 9: 3411-16.
40. Uckun FM, Mao C, Pendergrass S, Maher D, Zhu D, Tuel-Ahlgren L, et al. N-[2-(2-cyclohexenyl)ethyl]-N′-[2-(5-bromopyridyl)l-thiourea and N-[2-(2-cyclo hexenyl)ethyll-N′-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multigarug-resitant human immunodeficiency virus-1. Bioorg Med Chem Lett 19; 9: 2721-26.
41. Venkatachalam TK, Sudbeck EA, Mao C, Unckun FM. Anti-HIV activity of aromatic and heterocyclic thazolyl thiourea compounds. Bioorg Med Chem Lett 2001; 11: 523-28.
42. Venkatachalam. TK, Sudbeck EA, Mao C, Unckun FM. Piperidinethyl, phenoxyethyl and fluoroethyl bromopyridil thiourea compounds with potent anti-HIV activity. Antivir Chem Chemother 2000; 11: 329-36.
43. Ren J, Diproset J, Warren J, Esnouf RM, Bird LE, Ikemizu S, et al. Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptase. J Biol Chem 2000; 275: 5633-39.
44. 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 reverse transcriptase inhibitors. J Med Chem 1994; 37: 999-14.
45. Romero DL, Olmsted RA, Poel TJ, Morge RA, Biles C, Keiser BJ, et al. Targeting delarvidine/atervidine 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 M G, Poel TJ, Yagi Y, Biles C, Althaus C, Keiser BJ, et al. Synthesis and bioactivity of novel bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationship and increased metabolic stability of novel substituted pyridine analogs. J Med Chem 1996; 39: 5267-75.
47. Freimuth WW. Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. Adv Exp Med Biol 1996; 394: 279-89.
48. Tucker TJ, Lyle TA, Wiscount CM, Brichter SF, Young SD, Sanders WM, et al. Synthesis of a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3, 4-dihydroquinazolin-2(IH)-ones as novel non-nucleoside HIV- I reverse transcriptase inhibitors. J Med Chem 1994; 37: 2437-44.
49. Young SD, Brichter SF, Tran LO, Payne LS, Lumma WC, Lyle TA, et al. L-743, 726 (DMP-266): a novel nonnucleoside inhibitor of human immunodeficiency virus type I reverse transcriptase. Antimicrob Agents Chemother 1995; 39: 2602-05.
50. Graul A, Rabasseda X, Castaner J. Efavirenz. Antiviral for AIDS reverse transcriptase inhibitor. Drugs Fut 1998; 23: 133-41.
51. Corbett JW, Ko SS, Rodger JD, Jeffrey S, Bacheler LT, Klabe RM, Diamond S, et al. Expanded-spectrum non-nucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1999; 43: 2893-97.
52. Corbett JW, Gearhart LA, Soo S, Rodgers JD, Cordova BC, Klabe RM, et al. Novel 2, 2-dioxide-4, 4-disubstituted-1, 3-H-2, 1, 3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors. Bioorg Med Chem Lett 2000; 10: 193-95.
53. Magnus NA, Bacheler LT, Diamond S, Jeffrey S, Klabe RM, Garber S, et al. Inhibition of clinically relevant mutant variants of HIV-1 quinazolinone non-nnucleoside reverse transcriptase inhibitors. J Med Chem 2000; 43: 2019-30.
54. Corbett JW, Ko SS, Rodgers JD, Gearhart LA, Magnus NA, Bacheler LT, et al. Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors. J Med Chem 2000; 43: 2019-30.
55. Cocuzza A J, Chidester DR, Cordova BC, Jeffrey S, Parson RL, Bacheler LT, et al. Synthesis and evaluation of efavirenz (Sustiva™) analogues as HIV-1 reverse transcriptase inhibitors: replacement of the cyclopropylacetylene side chain. Bioorg Med Chem Lett 2001; 11: 1177-79.
56. Corbett JW, Kresge KJ, Pan S, Cordova BC, Klabe RM, Rodgers JD, et al. Trifluoromethyl-containing 3-alkoxymethyl and 3-aryloxymethyl-2-pyridones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase. Bioorg Med Chem Lett 2001; 11: 309-12.
57. Corbett JW, Rodgers JD. Discovery of scond generation quinazoline non-nucleoside reverse transcriptase inhibitors, in Progress in Medicinal Chemistry, Elsevier Science, 2002; Vol. 40, 63-05
58. Buckheit RW Jr, Kinjerski TL, Fliakas-Boltz V, Russel JD, Stup TL, Pallansch TL, et al. Structure-activity and cross-resitance evaluations of a series of human immunodeficiency virus type 1-specific compounds related to oxathiin carboxanilide. Antimicrob Agents Chemother 1995; 39: 2718-27.
59. Balzarini J, Brouwer WG, Felauer EE, De Clereq E, Karlsson A. Activity of various thiocarboxanilide derivatives against wild-type and several mutant immunodeficiency virus type 1 strains. Antiviral Res 1995; 27: 219-36.
60. Buckheit RW, Snow MJ, Fliakas-Boltz V, Kinjerski TL, Russel JD, Pallansch LA, et al. Highly potent oxathiin carboxanilide derivatives with efficacy against non-nucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus. Antimicrob Agents Chemother 1997; 41: 831-37.
61. Brokow G, Arion D, Wainberg MA, Parniak MA. The thiocarboxanilide nonnucleoside inhibitor UC781 restores antiviral activity of 3′-azido-3′-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 1999; 43: 259-63.
62. Hahn H-G, Rhee HK, Lee CK, Whang KJ. Designs and syntheses of oxathiin carboxanilide analogs and their antiviral activities. Arch Pharm Res 2000; 23: 315-23.
63. Hanasaki Y, Watanabe H, Katsuura K, Takayama H, Shirakawa S, Yamaguchi K, et al. Thiadiazole derivatives: highly potent and specific HIV-1 reverse transcriptase inhibitors. J Med Chem 1995; 38: 2038-40.
64. Ijichi K, Fujiwara M, Nagano H, Matsumoto Y, Hanasaki Y, Ide T, et al. Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity. Antiviral Res 19%; 31: 87-94.
65. Fujiwara M, Kodama EN, Okamoto M, Tokuhisa K, Ide T, Hanasaki Y, et al. Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217. Antiviral Chem Chemoth 1999; 10: 315-20.
66. Botta M, Artico M, Massa S, Gambacorta A, Marongiu ME, Pani A, et al. Synthesis, antimicrobial and antiviral activities of isotrimethoprim and some related derivatives. Eur J Med Chem 1992; 27: 251-57.
67. Artico M, Massa S, Mai A, Marongiu ME, Piras G, Tramontano E, et al, 3, 4-Dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs), a new class of specific inhibitors of human immunodeficiency virus type 1. Antiviral Chem Chemoth 1993; 4: 361-68.
68. Massa S, Mai A, Artico M, Sbardella G, Marongiu ME, Loi AG, et al. Synthesis and antiviral activity of new 3, 4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs), specific inhibitors of human inumodeficiency virus type 1. Antivir Chem Chemother 1995; 6: 1-8.
69. Mai A, Artico M, Sbardella G, Massa S, Loi AG, Tramontano E, et al. Synthesis and anti-HIV-1 activity of thio analogues of dihydro alkoxybenzyloxopyrimidines. J Med Chem 1995; 38: 3259-63.
70. Mai A, Artico M, Sbardella G, Quartarone S. Massa S,Loi AG, et al. Dihydro-alkyl-thio-naphthylmethyl-oxopyrimidines (IJATNOs), novel non nucleoside reverse transcriptase inhibitors to the S-DABOs series. J Med Chem 1997; 40: 1447-54.
71. Mai A, Artico M, Sbardella G, Novellino E, Greco G, Loi AG, et al. Alkyl-2-(alkylthio)-6-(2, 6-dihalophenylmethyl)-3, 4-dihydro-pyrimidin-4(3H)ones: novel potent and selective dihydro-alkoxy-benzyl-oxopyritnidine derivatives. J Med Chem 1999; 42: 619-27.
72. Sbardella G, Mai A, Artico M, Chimenti P, Massa S, Loddo R, et al. Structure-activity relationship studies on new DABOs: effect of substitutions at pyrilidine C-5 and C-6 positiobs on anti-HIV-1 activity. Antiviral Chem Chemoth 2001; 12: 37-50.
73. Artico M. Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002; 27: 159-75.
74. McMahon JB, Gulakowski RJ, Weialow OS, Shultz RJ, Narayanan VL, Clanton DJ, et al. Diarylsulphones, a new chemical class of normucleoside antiviral inhibitors of immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1993; 37: 754-60.
75. Stephens CE, Felder TM, Sowell JW Sr, Andrei G, Balzarini J, Snoeck R, et al. Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of dirarylsulfones. Bioorg Med Chem 2001; 9: 1123-32.
76. Buckheit RW Jr, Kliakas-Boltz V, Russel DJ, Snow M, Pallaush LA, Ynag SS, et al. diraylsulfone non-nucleoside reverse transcriptase inhibitor with a unique sensitivity profile to drug-resistance virus isolates. Antiviral Chem Chemoth 1996; 7: 243-52.
77. Chan JH, Hong SJ, Hunter III RN, Orr GF, Cowan JR, Sherman DB, et al. 2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1. J Med Chem 2001; 44: 1866-82.
78. Williams TM, Ciccarone M, MacTough SC, Rooney CS, Balani SK, Condra JH, et al. 5-Chloro-3-(phenylsulfonyl)indole-2-carboxyamide: a novel non-nucleoside inhibitor of the HIV-1 reverse transcriptase. J Med Chem 1993; 36: 1291-94.
79. Williams TA, Ciccarone TM, Saari WS, Wai JS, Greenlee WJ, Balani SK, et al. Indoles as inhibitors of HIV reverse transcriptase. Patent Application 1992; EP 0 530 907 Aq1.
80. Williams TA, Ciccarone TM, Greenlee WJ, Balani SK, Goldman ME, Hoffman JM Jr, et al. Patent Application 1994; WO 94/19321.
81. Artico M, Silvestri R, Stefancich G, Massa, Pagnozzi E, Musa D, et al. Synthesis of pyrryl aryl sulfones targeted at the HIV- 1 reverse transcriptase. Arch Pharm (Weinheim) 1995; 328: 223-29.
82. 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.
83. 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 (PASs), HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations. J Med Chem 2000; 43: 1886-91.
84. Artico M, Silvestri I, Massa S, Loi AG, La Colla, P. Piffil-(indolil-) aril-solfoni e relativo processo di produzione ed impiego nella terapia delle infezioni da virus. Patent Application 1995; M195AO00812,
85. Artico M, Massa S, Silvestri R, Loi AG, De Montis A, La Colla P. 1H-Pyrrol-1-yl and IH-indol-1-yl sulphones, processes for their preparation and use for therapy of HIV-1 infections. Patent Application 1996; WO 96/33171.
86. Artico M, Silvestri R, Pagnozzi E, Stefancich G, Massa S, Loi AG, et al. 5H-Pyrrolo[l, 2-b][1, 2, 5]benzothiadiazepines (PBTDs): a novel class of HIV-1-specific non-nucleoside reverse transcriptase inhibitors. Bioorg Med Chem 1996; 4: 837-50.
87. Silvestri R, Artico M, Pagnozzi E, Stefancich G, Massa S, La Colla P, et al. Synthesis and anti-HIV activity of 10, 11-dihydropyrrolo[1, 2-b][1, 2, 5]benzothiadiazepine-11-acetic acid 5, 5-dioxide derivatives and related compounds. Farmaco 1996; 51: 425-30.
88. Artico M, Massa S, Silvestri R, Loi AG, De Montis A, La Colla P. 1H-Pyrrol-1-yl and 1H-indol-1-yl sulphones, processes for their preparation and use for therapy of HIV-1 infections. Patent application 1996; WO 96/33171.
89. Silvestri R, De Martino G, Artico M, Massa S, Marceddu T, Loi AG, et al. Indolyl Aryl Sulfones (IASs). Part 1: SAR Studies and in vitro anti-HIV-1 activity against wt RT and related mutants. J Med Chem 2003; 46: 2482-93.
90. La Colla P, Artico M, Sommadossi, J.P. Phenylindoles for treatment of-RIV. Patent application 2002; US 10/122, 252.
91. Young SD, Amblard M, Brichter SF, Grey V, Tran LO, Lumma C Jr, et al. 2-Heterocyclic indole-3-sulfones as inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 1995; 5: 491-96.
92. La Colla P, Artico M., Sommadossi JP, Storer R, Moussa A. Substituted phenylindoles for treatment of HIV. US Provisional application 2002; 60/401: 915.
93. Silvestri R, Artico M, De Martino G, La Regina G, Loddo R, La Colla M, et al. Simple, short peptide derivatives of L-737,126 active in vitro against HIV-1 wt and variants carrying NNRTI resistance mutations. J Med Chem 2004; accepted.
94. Silvestri R, Artico M, Massa S, Marceddu T, De Montis F, La Colla P. 1-[2-(Diphenylmethoxy)cdiyl]-2-methyl-5-nitroimidazole: a potent lead for the design of novel NNRTIs. Bioorg Med Chem Lett 2000; 10: 253-56.
95. Silvestri R, Artico M, De Martino G, Ragno R, Massa S, Loddo I, et al. Synthesis, biological evaluation and binding mode of novel 1-[2-(diarylmethoxy)ethy1]2-methyl-5-nitroimidazoles targeted at the HIV- 1 reverse transcriptase. J Med Chem 2002; 45: 1567-76.
96. Bacheler L, Weislow O, Snyder S, Hanna G, D'Aquila R. SUSTIVA Resistance Team, Abstract from the 12th World AIDS Conference, Geneva (Switzerland), June 29 - July 3, 1998.
97. Hoetelmans RMV. Pharmacology of antiretroviral drugs. Antiviral Ther 1999; 4: 29-41.
98. Corbett JW, Ko SS, Rodger JD, Jeffrey S, Bacheler LT, Klabe RM, et al. Expanded-spectrum non-nucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1999; 43: 2893-97.
99. Corbett JW, Ko SS, Rodgers JD, Gearhart LA, Magnus NA, Bacheler LT, et al. Inhibition of clinically relevant mutant variants of HIV-1 quinazolinone non-nnucleoside reverse transcriptase inhibitors. J Med Chem 2000; 43: 2019-30.
100. Corbett JW, Rodgers JD. Discovery of scond generation quinazoline non-nucleoside reverse transcriptase inhibitors, in Progress in Medicinal Chemistry, Vol. 40,63-105, Elsevier Scienze 2002.
101. Patel M, McHugh RJ Jr, Cordova RM, Erickson-Vitanen S, Trainor GL, Ko SS. Synthesis and evaluation of benzoxazinones as HIV-1 reverse transcriptase inhibitors. Analogs of Efavirenz (SUSTIVA). Bioorg Med Chem Lett 1999; 9: 3221-24.
102. Guida WC, Mathre DJ, Phase-transfer alkylation of heterocycles in the presence of 18-crown-6 and potassium tert-butoxide. J Org Chem 1980; 45: 3172-76.
103. De Cat A, Van Pouke R. Sulfonyl fluorides as intermediates in organic synthesis. I. Synthesis of aminobenzene fluorides and their condensation with β-ketonic esters. J Org Chem 1963; 28: 3426-30.
104. Ketcha DM, Gribble GW. A convenient synthesis of 3-acylindoles via Friedel-Crafts acylation of 1-(phenylsulfonyl)indole. A new route to pyridocarbazole-5, 11-quinones and ellipticine. J Org Chem 1985; 26: 5451-57,
105. Atkinson JG, Hamel P, Girard Y. A new sythesis of 3-arylthioindoles. Synthesis 1988; 480-81.
106. Robinson, B. The Fischer indole synthesis, J. Wiley and Sons, Chirchester, New York, NY 1982.
107. Silvestri R, De Martino G, Sbardella G. A simplified synthesis of ethyl 5-chloro-6-fluoro-1H-indole-2-carboxy late and ethyl 5-chloro-4-fluoro-1H-indole-2-carboxylate. Organic Prep Proc Internat (OPPI) 2002; 34: 507- 10.
108. Silvestri R, Artico M, La Regina G, De Martino G. Synthetic Approaches to Difluoroindolecarboxylic Acid Ethyl Esters. Arkivoc 2004; V: 26-3 1.
109. Chen R, Quinones-Mateu ME, Mansky LM. Drug resistance, virus fitness and HIV-1 mutagenesis. Curr Pharm Design 2004; 10(32): 4065-70.
110. Imamichi T. Action of anti-HIV drugs and resistance: reverse transcriptase inhibitors and protease inhibitors. Curr Pharm Design 2004; 10(32): 4039-53.
111. Pereira CF, Paridaen JT. Anti-HIV drug development - an overview. Curr Pharm Design 2004; 10(32): 4005-37.