6-Benzylthioinosine Analogue Substrates of T. gondii
J ournal of Medicinal Chemistry, 2004, Vol. 47, No. 8 1993
6-(3-Meth ylben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6d ).
) 2.77, 12.35 Hz); 3.76 (dd, 1H, J ) 2.77, 12.40 Hz); 1.28 (s,
9H). Anal. (C21H26N4O4S): C, H, N, S.
Crystalline white solid. Yield ) 93%; mp 177-179 °C; [R]25
D
-58.507 (c 0.13, MeOH); UV (H2O) λmax 292 nm (ꢀ 32800 pH
2), 292 nm (ꢀ 31600 pH 7), 291.5 nm (ꢀ 32900 pH 11); 1H NMR
(CD3OD): δ ) 8.71 (s, 1H); 8.59 (s, 1H); 7.22-7.26 (m, 2H);
7.16 (t, 1H, J ) 7.46 Hz); 7.05 (d, 2H, J ) 6.38 Hz); 6.07 (d,
1H, J ) 5.7 Hz); 4.72 (t, 1H, J ) 5.65 Hz); 4.63 (s, 2H,); 4.33-
4.35 (m, 1H); 4.13-4.16 (m, 1H); 3.88 (dd, 1H, J ) 2.89, 12.53
Hz); 3.75 (dd, 1H, J ) 2.69, 12.42 Hz); 2.29 (s, 3H). Anal.
(C18H20N4O4S): C, H, N, S.
6-(4-Acetoxyben zylth io)-9-â-D-r ibofu r an osylpu r in e (6l).
Crystalline white solid. Yield ) 93%; mp 178-180 °C; [R]25
D
-61.260 (c 0.18, MeOH); UV (H2O) λ
291 nm (ꢀ 8000 pH
max
2), 290.5 nm (ꢀ 11500 pH 7), 285 nm (ꢀ 16600pH 11); 1H NMR
(CD3OD): δ ) 8.72 (s, 1H); 8.60 (s, 1H); 7.94 (d, 2H, J ) 8.07
Hz); 7.59 (d, 2H, J ) 8.17 Hz); 6.07 (d, 1H, J ) 5.68 Hz); 4.74
(s, 2H); 4.71 (t, 1H, J ) 5.18 Hz); 4.33-4.35 (m, 1H); 4.13-
4.16 (m,1H); 3.86-3.88 (m, 4H); 3.76 (dd, 1H, J ) 3.0, 12.59
Hz). Anal. (C19H20N4O6S): C, H, N, S.
6-(3-Tr iflu or om eth ylben zylth io)-9-â-D-r ibofu r an osylpu r -
in e (6e). Crystalline white solid. Yield ) 91%; mp 178-180
6-(4-Ch lor oben zylth io)-9-â-D-r ibofu r an osylpu r in e (6m ).
°C; [R]25 -42.611 (c 0.16, MeOH); UV (H2O) λmax 290.5 nm (ꢀ
Crystalline white solid. Yield ) 96%; mp 134-136 °C; [R]25
D
D
34900 pH 2), 290.5 nm (ꢀ 33600 pH 7), 290.5 nm (ꢀ 37000 pH
11); 1H NMR (CD3OD): δ ) 8.72 (s, 1H); 8.60 (s, 1H); 7.80 (s,
1H); 7.75 (d, 1H, J ) 7.23 Hz); 7.46-7.53 (m, 2H); 6.07 (d,
1H, J ) 5.7 Hz); 4.75 (s, 2H); 4.71 (t, 1H, J ) 5.39 Hz); 4.33-
4.35 (m, 1H); 4.13-4.16 (m, 1H); 3.88 (dd, 1H, J ) 2.85, 12.40
Hz); 3.76 (dd, 1H, J ) 3.13, 12.38 Hz). Anal. (C18H17F3N4O4S):
C, H, N, S.
-52.053 (c 0.26, MeOH); UV (H2O) λmax 291 nm (ꢀ 24700 pH
1
2), 291 nm (ꢀ 16900 pH 7), 291 nm (ꢀ 16700 pH 11); H NMR
(CD3OD): δ ) 8.72 (s, 1H); 8.60 (s, 1H); 7.44-7.47 (m, 2H);
7.27-7.29 (m, 2H); 6.07 (d, 1H, J ) 5.75 Hz); 4.71 (t, 1H, J )
5.41 Hz); 4.66 (s, 2H); 4.33-4.35 (m, 1H); 4.13-4.16 (m,1H);
3.88 (dd, 1H, J ) 2.85, 12.40 Hz); 3.76 (dd, 1H, J ) 3.13, 12.38
Hz). Anal. (C17H17ClN4O4S): C, H, N, S.
6-(3-Nit r ob en zylt h io)-9-â-D-r ib ofu r a n osylp u r in e (6f).
6-(4-Nitr oben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6n ).
Crystalline white solid. Yield ) 95%; mp 164-166 °C; [R]25
D
Crystalline white solid. Yield ) 94%; mp 197-198 °C; [R]25
D
-42.713 (c 0.14, MeOH); UV (H2O) λmax 286 nm (ꢀ 44100 pH
-58.152 (c 0.21, MeOH); UV (H2O) λmax 290 nm (ꢀ 38500 pH
1
2), 286 nm (ꢀ 41800 pH 7), 286 nm (ꢀ 39900 pH 11); H NMR
1
2), 289 nm (ꢀ 40300 pH 7), 289 nm (ꢀ 42700 pH 11); H NMR
(CD3OD): δ ) 8.73 (s, 1H); 8.61 (s, 1H); 8.40 (s, 1H); 8.09 (d,
1H, J ) 8.0 Hz); 7.9 (d, 1H, J ) 7.32 Hz); 7.53 (t, 1H, J ) 7.94
Hz); 6.07 (d, 1H, J ) 5.6 Hz); 4.78 (s, 2H); 4.70 (t, 1H, J )
5.37 Hz); 4.34 (t, 1H, J ) 3.59 Hz); 4.15 (d, 1H, J ) 2.97 Hz);
3.88 (dd, 1H, J ) 2.75, 12.48 Hz); 3.75 (dd, 1H, J ) 2.98, 12.32
Hz). Anal. (C17H17N5O6S): C, H, N, S.
(CD3OD): δ ) 8.72 (s, 1H); 8.61 (s, 1H); 8.16 (d, 2H, J ) 8.76
Hz); 7.73 (d, 2H, J ) 8.64); 6.07 (d, 1H, J ) 5.64 Hz); 4.79 (s,
2H); 4.70 (t, 1H, J ) 5.38 Hz); 4.33-4.35 (m, 1H); 4.13-4.16
(m,1H); 3.88 (dd, 1H, J ) 2.72, 12.53 Hz); 3.75 (dd, 1H, J )
3.12, 12.33 Hz). Anal. (C17H17N5O6S): C, H, N, S.
6-(4-Cya n oben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6o).
6-(4-Meth ylben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6g).
Crystalline white solid. Yield ) 93%; mp 72-74 °C; [R]25
D
Crystalline white solid. Yield ) 94%; mp 110-112 °C; [R]25
D
-49.651 (c 0.22, MeOH); UV (H2O) λmax 290.5 nm (ꢀ 48400 pH
2), 290.5 nm (ꢀ 32100 pH 7), 290.5 nm (ꢀ 47400 pH 11); 1H
NMR (CD3OD): δ ) 8.71 (d, 1H, J ) 1.52 Hz); 8.60 (d, 1H, J
) 1.38 Hz); 7.63-7.68 (m, 4H); 6.07 (d, 1H, J ) 5.67 Hz); 4.73
(s, 2H); 4.70 (t, 1H, J ) 5.08 Hz); 4.33-4.35 (m, 1H); 4.13-
4.15 (m,1H); 3.88 (dd, 1H, J ) 1.82, 12.32 Hz); 3.75 (dd, 1H, J
) 1.62, 12.28 Hz). Anal. (C18H17N5O4S): C, H, N, S.
-56.432 (c 0.37, MeOH); UV (H2O) λmax 292.5 nm (ꢀ 32300 pH
2), 292.5 nm (ꢀ 31100 pH 7), 292 nm (ꢀ 30200 pH 11); 1H NMR
(CD3OD): δ ) 8.70 (s, 1H); 8.58 (s, 1H); 7.32 (d, 2H, J ) 6.98
Hz); 7.1 (d, 2H, J ) 6.92 Hz); 6.07 (d, 1H, J ) 5.59 Hz); 4.71
(t, 1H, J ) 5.36 Hz); 4.62 (s, 2H,); 4.33-4.35 (m, 1H); 4.13-
4.16 (m, 1H); 3.88 (dd, 1H, J ) 2.8, 12.3 Hz); 3.76 (dd, 1H,
J ) 3.0, 12.36 Hz); 2.29 (s, 3H). Anal. (C18H20N4O4S): C, H,
N, S.
6-(4-F lu or oben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6p ).
Crystalline white solid. Yield ) 96%; mp 70-72 °C; [R]25
D
6-(4-Tr iflu or om et h oxyb en zylt h io)-9-â-D-r ib ofu r a n o-
sylp u r in e (6h ). Crystalline white solid. Yield ) 91%; mp 130-
-52.178 (c 0.18, MeOH); UV (H2O) λmax 291.5 nm (ꢀ 38100 pH
2), 291.5 nm (ꢀ 37700 pH 7), 291.5 nm (ꢀ 39000 pH 11); 1H
NMR (CD3OD): δ ) 8.72 (s, 1H); 8.59 (s, 1H); 7.48 (m, 2H);
7.01(m, 2H); 6.07 (d, 1H, J ) 5.73 Hz); 4.71 (t, 1H, J ) 5.37
Hz); 4.66 (s, 2H); 4.33-4.35 (m, 1H); 4.14-4.15 (m,1H); 3.88
(dd, 1H, J ) 2.84, 12.36 Hz); 3.76 (dd, 1H, J ) 3.06, 12.41
Hz). Anal. (C17H17FN4O4S): C, H, N, S.
132 °C; [R]25 -54.081 (c 0.19, MeOH); UV (H2O) λmax 290.5
D
nm (ꢀ 14300 pH 2), 290.5 nm (ꢀ 16000 pH 7), 291 nm (ꢀ 16400
pH 11); 1H NMR (CD3OD): δ ) 8.71 (s, 1H); 8.59 (s, 1H); 7.57
(d, 2H, J ) 8.27 Hz); 7.19 (d, 2H, J ) 7.64 Hz); 6.07 (d, 1H, J
) 5.36 Hz); 4.69-4.72 (m, 3H); 4.33-4.35 (m, 1H); 4.13-4.16
(m, 1H); 3.88 (dd, 1H, J ) 2.6, 12.15 Hz); 3.76 (dd, 1H, J )
2.47, 12.27 Hz). Anal. (C18H17F3N4O5S): C, H, N, S.
6-(2,4-Dich lor ob e n zylt h io)-9-â-D-r ib ofu r a n osylp u r -
in e (6q). Crystalline white solid. Yield ) 97%; mp 190 °C;
6-(4-Br om oben zylth io)-9-â-D-r ibofu r a n osylp u r in e (6i).
[R]25 -47.024 (c 0.14, MeOH); UV (H2O) λmax 284.5 nm (ꢀ
Crystalline white solid. Yield ) 97%; mp 156-158 °C; [R]25
D
D
10100 pH 2), 284.5 nm (ꢀ 9200 pH 7), 284.5 nm (ꢀ 11500 pH
11); 1H NMR (CD3OD): δ ) 8.74 (s, 1H); 8.60 (s, 1H); 7.67 (d,
1H, J ) 8.31 Hz); 7.48 (d, 1H, J ) 2.04 Hz), 7.26 (dd, 1H, J )
2.08, 8.31 Hz); 6.07 (d, 1H, J ) 5.68 Hz); 4.77 (s, 2H); 4.71 (t,
1H, J ) 5.26 Hz); 4.33-4.35 (m, 1H); 4.14-4.16 (m,1H); 3.88
(dd, 1H, J ) 2.76, 12.35 Hz); 3.76 (dd, 1H, J ) 3.06, 12.40
Hz). Anal. (C17H16Cl2N4O4S): C, H, N, S.
-48.688 (c 0.23, MeOH); UV (H2O) λmax 291.5 nm (ꢀ 28700 pH
2), 291.5 nm (ꢀ 11800 pH 7), 291.5 nm (ꢀ 17900 pH 11);1H NMR
(CD3OD): δ ) 8.71 (s, 1H); 8.59 (s, 1H); 7.38-7.44 (m, 4H);
6.07 (d, 1H, J ) 5.75 Hz); 4.71 (t, 1H, J ) 5.38 Hz); 4.64 (s,
2H); 4.33-4.35 (m, 1H); 4.13-4.16 (m,1H); 3.88 (dd, 1H, J )
2.8, 12.39 Hz); 3.75 (dd, 1H, J ) 3.08, 12.37 Hz). Anal. (C17H17
-
BrN4O4S): C, H, N, S.
6-(2-Ch lor o-6-flu or oben zylth io)-9-â-D-r ibofu r an osylpu r -
in e (6r ). Crystalline white solid. Yield ) 94%; mp 102-104
6-(4-Meth oxyben zylth io)-9-â-D-r ibofu r an osylpu r in e (6j).
Crystalline white solid. Yield ) 93%; mp 102-104 °C; [R]25
D
°C; [R]25 -55.583 (c 0.18, MeOH); UV (H2O) λmax 290.5 nm (ꢀ
-50.844 (c 0.43, MeOH); UV (H2O) λmax 292.5 nm (ꢀ 32800 pH
2), 292.5 nm (ꢀ 31600 pH 7), 292 nm (ꢀ 31100 pH 11); 1H NMR
(CD3OD): δ ) 8.71 (s, 1H); 8.58 (s, 1H); 7.36 (d, 2H, J ) 8.6
Hz); 6.84 (d, 2H, J ) 8.65 Hz); 6.07 (d, 1H, J ) 5.77 Hz); 4.71
(t, 1H, J ) 5.40 Hz); 4.62 (s, 2H); 4.33-4.35 (m, 1H); 4.13-
4.16 (m,1H); 3.88 (dd, 1H, J ) 2.73, 12.43 Hz); 3.74-3.77 (m,
4H). Anal. (C18H20N4O5S): C, H, N, S.
D
38500 pH 2), 290.5 nm (ꢀ 37400 pH 7), 290.5 nm (ꢀ 38800 pH
1
11); H NMR (CD3OD): δ ) 8.76 (s, 1H); 8.60 (s, 1H); 7.28-
7.35 (m, 2H); 7.9-7.14 (m, 1H); 6.09 (d, 1H, J ) 5.64 Hz); 4.87
(s, 2H); 4.72 (t, 1H, J ) 5.43 Hz); 4.33-4.35 (m, 1H); 4.13-
4.16 (m,1H); 3.89 (dd, 1H, J ) 2.50, 12.15 Hz); 3.76 (dd, 1H, J
) 2.91, 12.42 Hz). Anal. (C17H16FClN4O4S): C, H, N, S.
6-(4-ter t-Bu t ylb en zylt h io)-9-â-D-r ib ofu r a n osylp u r in e
6-(3,4-Dich lor ob e n zylt h io)-9-â-D-r ib ofu r a n osylp u r -
in e (6s). Crystalline white solid. Yield ) 95%;mp 144-146
°C; [R]25 D -53.048 (c 0.25, MeOH); UV (H2O) λmax 290.5 nm (ꢀ
38300 pH 2), 290.5 nm (ꢀ 35500 pH 7), 290.5 nm (ꢀ 32200 pH
11); 1H NMR (CD3OD): δ ) 8.72 (s, 1H); 8.60 (s, 1H); 7.65 (s,
1H); 7.42 (s, 2H); 6.07 (d, 1H, J ) 5.64 Hz); 4.71 (t, 1H, J )
5.28 Hz); 4.64 (s, 2H); 4.34 (t, 1H, J ) 4.01 Hz); 4.15 (d,1H, J
(6k ). Crystalline white solid. Yield ) 92%; mp 74-76 °C; [R]25
D
-43.770 (c 0.16, MeOH); UV (H2O) λmax 292.5 nm (ꢀ 29400 pH
2), 292.5 nm (ꢀ 29800 pH 7), 292.5 nm (ꢀ 31700 pH 11); 1H
NMR (CD3OD): δ ) 8.71 (s, 1H); 8.58 (s, 1H); 7.31-7.38 (m,
4H); 6.07 (d, 1H, J ) 5.76 Hz); 4.72 (t, 1H, J ) 5.41 Hz); 4.64
(s, 2H); 4.33-4.35 (m, 1H); 4.14-4.16 (m,1H); 3.88 (dd, 1H, J