Chemistry Reference
In-Depth Information
TABLE 9-10. Anti-HIV Activity of Additional C-28 Modified
Betulinic Acid Derivatives
65
H
H
O
O
H
H
Y
HN
NH(CH
2
)
7
-CONRR'
H
(CH
2
)
7
H
COOH
HO
HO
H
H
251-255
230-250
Compound
CEM Cells IC
50
(mM)
MT-4 Cells IC
50
(mM)
230 NRR
0
¼
Ala
0.092
0.062
231 NRR
0
¼
NHC(CH
3
)
2
COOH
0.133
0.089
232 NRR
0
¼
L-Ser
0.25
0.25
233 NRR
0
¼
D-Ser
1.9
Nt
234 NRR
0
¼
Sarcosine
0.25
0.33
235 NRR
0
¼
Pro
0.64
0.058
240
0.085
0.047
241
0.13
Nt
242
0.13
Nt
243
0.095
Nt
244
0.155
Nt
245
0.185
Nt
246
0.05
0.04
247
0.2
0.033
248
0.052
0.085
249
0.13
0.033
250
0.05
0.044
252
0.08
Nt
253
0.105
0.04
255
0.07
0.026
256
0.11
0.022
nevirapine
0.084
Nt, not detected.
p-aminobenzoic acid derivatives (251-253) and corresponding benzenedicarboxylic
acid derivatives (254-256) were synthesized (Figure 9-11). The ortho-derivative
(251 and 254) was inactive, probably because of steric hindrance. The meta- and
para-derivatives (252, 253, 255, and 256, Table 9-10) were active. The statine deri-
vative 246 (RPR103611) was found to display the best overall activity, with an IC
50
value of 0.050
0.026 mM in CEM cells and 0.040
0.019 mM in MT-4 cells and
low cytotoxicity (SI
>
100). Therefore, RPR103611 (246) was selected for contin-
ued investigations.
65
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