Biomedical Engineering Reference
In-Depth Information
24.2.3 N
ONNUCLEOSIDE
R
EVERSE
T
RANSCRIPTASE
I
NHIBITORS
(NNRTI
S
)
24.2.3.1 Nevirapine
Structure
(Figure 24.4): 11-Cyclopropyl-5,11-dihydro-4-methyl-6
H
-dipyrido[3,2-b:2
′
,3
′
-f ][1,4]
diazepin-6-one, Viramune
®
.
Activity spectrum
: HIV type 1.
Mechanism of action
: Targeted at an allosteric “pocket,” nonsubstrate binding site of the HIV-1 RT
(as illustrated in Figure 24.5 for Etravirine, an NNRTI currently in clinical development).
CH
3
CH
3
CH
3
CH
O
N
SO
2
CH
3
NH
F
3
C
Cl
NH
O
N
N
N
H
N
N
N
H
O
O
CH
3
SO
3
H
Nevirapine
Delavirdine
Efavirenz
FIGURE 24.4
Structures of a number of nonnucleoside RT inhibitors (NNRTIs).
W229
L234
P225
F227
Y188
V108
Y318
Y181
L100
P230
Q138
K101
V106
K103
V179
FIGURE 24.5
Etravirine (TMC125) positioned in NNRTI-binding site of HIV-1 RT. (After Pauwels, R.,
Curr. Opin. Pharmacol
., 4, 437, 2004.)
