Antiviral Drugs - Drug Design and Discovery - page 403

Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally at 2400 mg/day (eight 150 mg capsules twice a day, to be taken with or without
food, but not with a high-fat meal). If “boosted” with ritonavir, 600 mg amprenavir/100 mg ritonavir
twice daily.
24.2.4.6 Lopinavir
Structure (Figure 24.6): N -(4( S )-(2-(2,6-Dimethylphenoxy)-acetylamino)-3( S )-hydroxy-5-phenyl-1( S )-
benzylpentyl)-3-methyl-2( S )-(2-oxo(1,3-diazaperhydroinyl)butanamine, combined with ritonavir at
4:1 ratio; ABT-378/r, Kaletra ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally, as Kaletra, at 1000 mg/day (three 166.6 mg capsules twice a day; each capsule
containing 133.3 mg lopinavir + 33.3 mg ritonavir), to be taken with food.
24.2.4.7 Atazanavir
Structure (Figure 24.6): 1-[4-(Pyridin-2-yl)phenyl]-5( S )-2,5-bis-{[ N -(methoxycarbonyl)-l- tert -
leucinyl]amino}-4( S )-hydroxy-6-phenyl-2-azahexane, CGP 73547, BMS-232632, Reyataz ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally at 400 mg/day (once daily two 200 mg capsules), to be taken with food.
24.2.4.8 Fosamprenavir
Structure (Figure 24.6): (3 S )-Tetrahydrofuran-3-yl (1 S ,2 R )-3-[[(4-aminophenyl) sulfonyl](isobutyl)
amino]-1-benzyl-2-(phosphonooxy) propylcarbamate monocalcium salt, Lexiva ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally at 1400 mg (two 700 mg tablets) twice daily without ritonavir; or 1400 mg (two
700 mg tablets) once daily with ritonavir 200 mg once daily; or 700 mg twice daily plus ritonavir
100 mg twice daily.
24.2.4.9 Tipranavir
Structure (Figure 24.6): 2-Pyridinesulfonamide, N -[3-[(1 R )-1-[(6 R )-5,6-dihydro-4-hydroxy-2-oxo-
6-(2-phenylethyl)-6-propyl-2 H -pyran-3-yl]propyl]phenyl]-5-(tril uoromethyl), Aptivus ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Nonpeptidomimetic inhibitor of HIV protease.
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally as 250 mg capsules, boosted by ritonavir: 500 mg tipranavir/200 mg ritonavir
twice daily.
24.2.4.10 Darunavir
Structure (Figure 24.6): [(1 S ,2 R )-3-[[(4-Aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-
1-(phenylmethyl)propyl]-carbamic acid (3 R ,3a S ,6a R )-hexahydrofuro[2,3- b ]furan-3-yl ester mono-
ethanolate, Prezista ® .