Compositions containing two or three inhibitors of different HIV

Details Compositions containing two or three inhibitors of different HIV Compositions containing two or three inhibitors of different HIV

1994-11-30

1999-10-19

Kight, John

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 46, 514 49, 514 50, 514448, 514471, 536 276, 536 278, 536 2781, 536 284, 536 285, 536 2851, 536 2852, 536 2853, 536 2854, 536 2855, 536 287, 549 71, 549506, A61K 3170

Patent

active

059689102

ABSTRACT:
A composition and method for the prevention or treatment of HIV-1 infection comprising an HIV-1 reverse transcriptase-inhibiting heterocyclyl carb(ox/thio)anilide compound, a second HIV-1 reverse transcriptase inhibitor compound which does not select for the same HIV-1 mutant strain or strains selected for by the heterocyclyl carb(ox/thio)anilide compound, and, optionally, a third HIV reverse transcriptase inhibitor compound.

REFERENCES:
patent: 5268389 (1993-12-01), Harrison
Balzarini et al, "2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxathio le-2",2"-dioxide)pyrimidine (TSAO) nucleoside analogues: Highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase", Proc. Natl. Acad. Sci. USA, 89: 4392-4396 (May 1992).
Camarasa et al, "3'-Spiro Nucleosides, a new Class of Specific Human Immunodeficiency Virus Type 1 Inhibitors: Synthesis and Antiviral Activity of [2',5'-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-xylo-and -ribofuranose]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-Dioxide)(TSAO)P yrimidine Nucleosides", J. Med. Chem. 35: 2721-2727 (1992).
Perez-Perez et al, "TSAO analogues. Stereospecific Synthesis and Anti-HIV-1 Activity of 1-[2',5'-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro- 5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide)Pyrimidine and Pyrimidine-Modified Nucleosides", J. Med. Chem., 35: 2988-2995 (1992).
Balzarini et al, "Treatment of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells with Combination of HIV-1-Specific Inhibitors Results in a Different Resistance Pattern Than Does Treatment with Single-Drug Therapy", J. Virol., 67(9): 5353-5359 (Sep. 1993).
Balzarini et al, "HIV-1-Specific Reverse Transcriptase Inhibitors Show Differential Activity against HIV-1 Mutant Strains Containing Different Amino Acid Substitutions in the Reverse Transcriptase", Virology, 192: 246-253 (1993).
Balzarini et al, "TSAO derivatives: highly specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors", Drugs of the Future 1993, 18(11): 1043-1055.
Velazquez et al., TSAO Analogues. 3. Synthesis and Anti-HIV-1 Activity of 2',5'-Bis-O-(tert-Butyldimethylsilyl)-.beta.-D-ribofuranosyl 3'-Spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) Purine and Purine-Modified Nucleosides, J. Medicinal Chem., 36(22), 3230-3239 (1993).
Balzarini et al.(I), "Knocking-Out Concentration of HIV-1-Specific Inhibitors Completely Suppress HIV-1 Infection and Prevent the Emergence of Drug-Resistant Virus," Virology, 196(2), 576-585 (1993).
Balzarini et al. (II), "Human Immunodeficiency Virus Type 1 (HIV-1) Strains Selected for Resistance Against the HIV-1-Specific [2',5'-Bis-O-(tert-Butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxathio le-2",2"-dioxide)]-.beta.-D-pentofuranosyl (TSAO) Nucleoside Analogues Retain Sensitivity to HIV-1-Specific Nonnucleoside Inhibitors," Proc. Nat. Acad. Sci. USA, 90(15), 6952-6956 (1993).
Balzarini et al (III), "Kinetics of Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase by the Novel HIV-1-Specific Nucleoside Analogue [2',5'-Bis-O-(tert-Butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5" -(4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine (TSAO-T)," J. Biol. Chem., 267(17), 11831-11838 (1992).
Balzarini et al. (IV), "[2', 5'-Bis-O-(tert-Butyldimethylsilyl)]-3'-spiro-5"-(4"-amino-1",2"-oxathiole- 2",2"-dioxide) (TSAO) Derivatives of Purine and Pyrimidine Nucleosides as Potent and Selective Inhibitors of Human Immunodeficiency Virus Type 1," Antimicrobial Agents and Chemotherapy, 36(5), 1073-1080 (1992).
Balzarini et al. (V), "Supression of the Breakthrough of Human Immunodeficiency Virus Type 1 (HIV-1) in Cell Culture by Thiocarboxanilide Derivatives When Used Individually or in Combination with Other HIV-1-Specific Inhibitors (i.e. TSAO Derivatives)," Proc. Nat. Acad. Sci. USA, 92(12), 5470-5474 (1995).
E. De Clercq, "Non-nucleoside reverse transcriptase inhibitors (NNRTIs)", Exp. Opin. Invest. Drugs 3(3): 253-271 (1994) (Mar.).
E. De Clercq, "Resistance of Human Immunodeficiency Virus Type 1 (HIV-1) to Non-nucleoside HIV-1 Specific Reverse Transcriptase Inhibitors", Int. J. Immunotherapy X(4): 145-158 (1994).
Kilby et al, "Is There a role for Non-nucleoside Reverse Transcriptase Inhibitors in the Treatment of HIV Infection?", Infectious Agents and Disease 3(6): 313-323 (1994).
D. L. Romero, "Delavirdine Mesylate", Drugs of the Future 19(3): 238-242 (1994).
M. A. Fischl, "Combination Antiretroviral Therapy for HIV Infection", Hospital Practice: 43-48 (Jan. 15, 1994).
T. B. Campbell, "New antiretroviral agents for the therapy of HIV type-1 infection", Current Opinion in Infectious Diseases 6: 768-772 (1993) Dec.

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