Antiplasmodial activity and cytotoxicity of the synthesized 2-aminothieno[3,2-d]pyrimidin4(3H)-ones.
| ||||||
|---|---|---|---|---|---|---|
| Entry | R1 | R2 | EC50PfK1 (μM) | CC50 HepG2 (μM) | SI | c log D7.4b |
| 1 | Br | tBu | 43.2 ± 2.6 | 38.2 ± 3.5 | 0.9 | 3.19 |
| 3 | iPr | >50 | 89.1 ± 9.7 | <1.8 | 2.91 | |
| 1a | 4-Me–Ph–NH– | tBu | 10.3 ± 0.2 | 21.7 ± 2.1 | 2.1 | 4.38 |
| 1b | 3-Me–Ph–NH– | tBu | 1.1 ± 0.3 | 5.3 ± 0.4 | 4.8 | 4.38 |
| 1c | 2-Me–Ph–NH– | tBu | 4.3 ± 0.2 | 14.1 ± 0.3 | 3.3 | 4.38 |
| 1d | 4-MeO–Ph–NH– | tBu | 7.2 ± 2.0 | 24.0 ± 3.1 | 3.3 | 3.71 |
| 1e | 4 F–Ph–NH– | tBu | 7.1 ± 1.4 | 21.3 ± 1.6 | 3.0 | 4.01 |
| 1f | Morpholinyl– | tBu | 4.5 ± 1.1 | >50 | >11.1 | 2.31 |
| 1g | Piperidinyl– | tBu | 0.77 ± 0.13 | 33.9 ± 1.4 | 44.0 | 3.38 |
| 2b | 4-Me–Ph– | tBu | 2.35 ± 0.38 | >12.5 | >5.3 | 5.03 |
| 2c | iPr | 4.6 ± 1.0 | 3.1 ± 0.6 | 0.7 | 4.75 | |
| 2d | HO(CH2)2– | tBu | >10 | >50 | — | 2.39 |
| 2e | Cyclopropyl– | tBu | 1.9 ± 0.6 | 20.8 ± 1.4 | 10.9 | 3.65 |
| 2f | H– | tBu | >12.5 | 4.7 ± 1.0 | <0.4 | 2.54 |
| 2g | N-Methylpiperazine–CH2– | tBu | >5 | 41.6 ± 5.2 | <8.3 | 2.20 |
| 2h | Ph– | iPr | 2.8 ± 1.0 | >12.5 | >4.5 | 4.23 |
| 4a | 4-CO2Me–Ph– | tBu | 2.5 ± 0.9 | >12.5 | >5.0 | 3.91 |
| 4d | 4-HO–Ph– | tBu | 7.5 ± 1.0 | 12.2 ± 0.3 | 1.6 | 3.60 |
| 4e | 3-Cl-4-F–Ph– | tBu | 2.0 ± 0.9 | >12.5 | >6.3 | 4.65 |
| 4f | iPr | 3.6 ± 1.2 | >6.25 | >1.7 | 4.37 | |
| 4g | 4-Morpholinyl–Ph– | tBu | 2.4 ± 0.9 | 7.9 ± 1.3 | 3.3 | 3.79 |
| 4h | 4-(N-Methylpiperazinyl)–Ph– | tBu | 4.1 ± 0.7 | 5.8 ± 0.5 | 1.4 | 3.29 |
| 4i | 4-Piperidinyl–Ph- | tBu | 4.1 ± 1.2 | >6.25 | >1.5 | 4.86 |
| 4j | 4-MeS–Ph– | tBu | 1.0 ± 0.3 | >12.5 | >12.5 | 4.53 |
| 4k | 4-MeSO2–Ph– | tBu | 3.0 ± 0.6 | >25 | >8.3 | 2.74 |
| 4l | 4-(H2N–SO2)–Ph– | tBu | >12.5 | >6.25 | — | 2.51 |
| 4m | 4-(Morpholinyl–SO2)–Ph– | tBu | 5.1 ± 2.6 | >12.5 | >2.5 | 2.74 |
| 4n | 2-Morpholinopyrimidin-5-yl– | tBu | 2.1 ± 0.6 | 26.4 ± 4.6 | 12.6 | 2.55 |
| 4o | 2-(N-Methylpyperazin-1-yl)pyrimidin-5-yl– | tBu | 4.4 ± 1.0 | 11.2 ± 1.3 | 2.5 | 2.40 |
| 4p | 4-NH2-Ph– | tBu | 3.5 ± 1.2 | 2.5 ± 1.0 | 0.7 | 3.07 |
| 4q | iPr | 6.0 ± 1.1 | 11.3 ± 3.5 | 1.9 | 2.79 | |
| 4r | 4-(CH3–CO–NH)-Ph– | tBu | 3.9 ± 1.1 | 0.16 ± 0.04 | <0.1 | 3.14 |
| 4s | 4-(CH3–SONH)-Ph– | tBu | >12.5 | 63.3 ± 14.6 | <5.1 | 2.76 |
| M1 a | 0.045 | 24 | 533 | 4.42 | ||
| M1 (free base) a | 0.2 | 25.6 | 128 | 4.42 | ||
| Chloroquine a | 0.5 | 30 | 60 | 0.88 | ||
| Atovaquone a | 0.0013 | >15.6 | >12 000 | 4.37 | ||
| Doxycycline a | 5 | 20 | 4 | −0.80 | ||
| Doxorubicine a | — | 0.2 | — | 0.04 | ||
a
Values from ref. 9.
b
See experimental part for details.