Antiviral Drugs - Drug Design and Discovery - page 402

FIGURE 24.7 HIV protease structure with Darunavir (TMC114) in the active site. (After Pauwels, R.,
Antiviral Res ., 71, 77, 2006.)

24.2.4.3 Indinavir
Structure (Figure 24.6): [(1 S ,2 R ,5( S )-2,3,5-Trideoxy- N -(2,3-dihydro-2-hydroxy-1 H -inden-1-yl)-
5-[2-[[(1,1-dimethylethyl)amino]carbonyl]-4-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl-d-
erythro)pentonamide, Crixivan ® .
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 2400 mg/day (two 400 mg capsules every 8 h to be taken on empty stomach),
plus hydration (at least 1.5 L liquid daily). If “boosted” with ritonavir, 800 mg indinavir/100 mg
ritonavir twice daily.

24.2.4.4 Nelfi navir
Structure (Figure 24.6): [3 S -(3 R ,4a R ,8a R ,2 ′ S )]-2-[2 ′ -Hydroxy-3 ′ -phenylthiomethyl-4 ′ -aza-5 ′ -oxo-5 ′ -

-hydroxyphenyl)-pentyl]-3-( N -( tert -butyl)-carboxamide)-decahydro isoquinoline methane
sulfonate, Viracept ® .
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 2250 mg/day (three 250 mg tablets three times a day) or 2500 mg/day (i ve
250 mg tablets twice a day), to be taken with a meal.

[2 ′ -methyl-3 ′

24.2.4.5 Amprenavir
Structure (Figure 24.6): (3 S )-Tetrahydro-3-furyl- N -[( S ,2 R )-3-(4-amino- N -isobutylbenzene-sulfonamido)-
1-benzyl-2-hydroxypropyl]carbamate, Agenerase ® , Prozei ® .
Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.