Table 2.
Comp. | HBDa | HBAb | RBNc | logPd | logSe | PSAf | HIAg | PPBh | BBBi | CYP3A4j | T1/2 (h)k | HTl | LD50(mg/kg)m |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
6a | 0 | 10 | 11 | 1.84 | −2.23 | 96.79 | 0.81 | 0.68 | 0.94 | 0 | 2.02 | 0 | 459.04 |
6b | 0 | 10 | 12 | 1.90 | −1.93 | 96.79 | 0.80 | 0.67 | 0.91 | 0 | 2.13 | 0 | 429.48 |
6c | 0 | 10 | 13 | 2.48 | −2.05 | 96.79 | 0.80 | 0.68 | 0.91 | 0 | 2.14 | 0 | 462.17 |
6d | 0 | 10 | 15 | 3.39 | −2.02 | 96.79 | 0.80 | 0.65 | 0.91 | 0 | 2.12 | 0 | 447.58 |
6e | 0 | 10 | 17 | 4.31 | −1.90 | 96.79 | 0.80 | 0.65 | 0.91 | 0 | 2.14 | 0 | 425.74 |
6f | 0 | 10 | 19 | 5.22 | −1.67 | 96.79 | 0.80 | 0.66 | 0.91 | 0 | 2.18 | 0 | 460.97 |
6g | 0 | 10 | 21 | 6.13 | −1.35 | 96.79 | 0.80 | 0.67 | 0.91 | 0 | 2.23 | 0 | 508.77 |
6h | 0 | 6 | 4 | 0.97 | −2.49 | 51.75 | 0.79 | 0.67 | 0.98 | 0 | 2.00 | 0 | 664.69 |
6i | 1 | 6 | 6 | 0.47 | −1.52 | 69.21 | 0.78 | 0.70 | 0.75 | 0 | 1.77 | 0 | 1011.08 |
8a | 2 | 6 | 6 | −0.09 | −1.53 | 105.27 | 0.69 | 0.78 | 0.98 | 0 | 1.81 | 1 | 1027.40 |
8b | 2 | 6 | 7 | 0.49 | −1.87 | 105.27 | 0.72 | 0.79 | 0.98 | 0 | 1.88 | 1 | 988.28 |
8c | 2 | 6 | 9 | 1.40 | −2.30 | 105.27 | 0.72 | 0.80 | 0.98 | 0 | 1.89 | 1 | 1033.87 |
8d | 2 | 6 | 11 | 2.31 | −2.67 | 105.27 | 0.72 | 0.83 | 0.98 | 0 | 1.92 | 1 | 1099.10 |
8e | 2 | 6 | 13 | 3.22 | −2.97 | 105.27 | 0.72 | 0.85 | 0.98 | 0 | 2.03 | 1 | 1278.93 |
8f | 2 | 6 | 15 | 4.14 | −3.21 | 105.27 | 0.72 | 0.85 | 0.98 | 0 | 2.01 | 1 | 1318.54 |
9e | 2 | 2 | 15 | 6.21 | −4.45 | 60.22 | 0.69 | 0.89 | 0.99 | 0 | 1.93 | 1 | 961.82 |
10e | 2 | 4 | 13 | 2.97 | −2.60 | 82.74 | 0.70 | 0.91 | 0.99 | 0 | 1.85 | 1 | 1075.58 |
11e | 2 | 2 | 13 | 5.27 | −4.27 | 60.22 | 0.68 | 0.91 | 1.00 | 0 | 1.96 | 1 | 1653.45 |
12e | 2 | 2 | 13 | 7.09 | −6.11 | 60.22 | 0.69 | 0.92 | 0.99 | 0 | 2.12 | 1 | 1818.99 |
13e | 2 | 4 | 13 | 2.97 | −2.60 | 82.74 | 0.72 | 0.91 | 0.99 | 0 | 1.89 | 0 | 1070.63 |
14e | 2 | 2 | 13 | 4.06 | −3.66 | 85.33 | 0.41 | 0.90 | 1.00 | 0 | 1.78 | 0 | 1145.12 |
15e | 2 | 4 | 13 | 3.83 | −3.35 | 82.74 | 0.70 | 0.91 | 0.99 | 0 | 1.89 | 1 | 1128.86 |
16e | 2 | 6 | 13 | 1.53 | −1.68 | 105.27 | 0.68 | 0.85 | 0.99 | 0 | 1.82 | 1 | 1461.77 |
17e | 2 | 4 | 13 | 5.65 | −5.10 | 82.74 | 0.70 | 0.95 | 0.98 | 0 | 2.22 | 1 | 1217.90 |
18e | 2 | 4 | 13 | 5.65 | −5.10 | 82.74 | 0.72 | 0.96 | 0.95 | 0 | 1.99 | 1 | 1254.91 |
19e | 4 | 4 | 13 | 4.31 | −4.38 | 112.85 | 0.69 | 0.90 | 0.94 | 0 | 1.91 | 1 | 1167.64 |
20e | 2 | 6 | 13 | 5.33 | −4.57 | 112.68 | 0.43 | 0.93 | 0.98 | 0 | 2.29 | 0 | 973.08 |
21e | 2 | 2 | 13 | 6.46 | −6.02 | 85.33 | 0.47 | 0.94 | 0.99 | 0 | 2.00 | 1 | 966.72 |
22e | 2 | 2 | 13 | 7.40 | −6.99 | 60.22 | 0.69 | 0.91 | 0.99 | 0 | 2.07 | 1 | 904.88 |
23e | 2 | 2 | 13 | 6.27 | −5.55 | 70.92 | 0.75 | 0.95 | 0.99 | 0 | 2.27 | 1 | 995.92 |
24e | 4 | 2 | 13 | 5.86 | −5.15 | 90.33 | 0.72 | 0.95 | 0.96 | 0 | 2.01 | 1 | 1072.61 |
25e | 2 | 2 | 15 | 7.54 | −5.78 | 60.22 | 0.67 | 0.89 | 0.99 | 0 | 1.98 | 1 | 1322.11 |
26e | 4 | 6 | 17 | 5.69 | −3.28 | 119.71 | 0.45 | 0.87 | 0.85 | 0 | 1.93 | 1 | 1249.90 |
27e | 2 | 6 | 19 | 6.14 | −3.64 | 95.94 | 0.54 | 0.82 | 0.98 | 0 | 1.82 | 1 | 1217.58 |
28e | 4 | 8 | 19 | 5.66 | −3.13 | 137.57 | 0.46 | 0.77 | 0.94 | 0 | 2.02 | 1 | 1163.97 |
29e | 2 | 8 | 21 | 6.11 | −3.08 | 113.80 | 0.54 | 0.73 | 0.96 | 0 | 1.95 | 0 | 927.46 |
30e | 4 | 4 | 13 | 3.78 | −2.74 | 113.30 | 0.59 | 0.90 | 0.99 | 0 | 1.96 | 1 | 849.92 |
31e | 4 | 4 | 13 | 3.78 | −2.69 | 113.30 | 0.64 | 0.90 | 0.97 | 0 | 1.93 | 0 | 951.43 |
32e | 4 | 4 | 13 | 3.78 | −2.72 | 113.30 | 0.64 | 0.90 | 0.98 | 0 | 1.94 | 0 | 853.84 |
33e | 2 | 6 | 17 | 5.21 | −3.97 | 95.94 | 0.53 | 0.81 | 0.99 | 0 | 1.76 | 0 | 1184.47 |
34e | 2 | 8 | 19 | 5.18 | −3.62 | 113.80 | 0.54 | 0.76 | 0.98 | 0 | 1.63 | 0 | 1073.30 |
35e | 2 | 8 | 19 | 5.18 | −3.67 | 113.80 | 0.53 | 0.76 | 0.97 | 0 | 1.72 | 0 | 1061.01 |
9d | 2 | 2 | 13 | 5.30 | −4.11 | 60.22 | 0.69 | 0.91 | 0.99 | 0 | 1.92 | 1 | 1523.97 |
9f | 2 | 2 | 17 | 7.12 | −4.73 | 60.22 | 0.69 | 0.87 | 0.99 | 0 | 1.95 | 0 | 1003.19 |
9g | 0 | 4 | 15 | 6.59 | −5.34 | 52.46 | 0.55 | 0.88 | 0.98 | 0 | 1.96 | 1 | 6181.36 |
9h | 0 | 4 | 17 | 7.50 | −5.69 | 52.46 | 0.55 | 0.86 | 0.98 | 0 | 1.96 | 1 | 4624.51 |
9i | 0 | 4 | 19 | 8.42 | −5.96 | 52.46 | 0.55 | 0.85 | 0.98 | 0 | 1.96 | 0 | 3127.76 |
9j | 2 | 4 | 13 | 2.57 | −2.06 | 78.08 | 0.37 | 0.86 | 0.99 | 0 | 1.97 | 1 | 1574.67 |
9k | 2 | 5 | 16 | 2.44 | −1.41 | 87.01 | 0.37 | 0.85 | 0.99 | 0 | 1.90 | 0 | 1693.04 |
9l | 0 | 6 | 15 | 3.86 | −2.96 | 70.32 | 0.50 | 0.88 | 0.98 | 0 | 1.89 | 1 | 4511.05 |
9m | 0 | 7 | 18 | 3.73 | −2.14 | 79.25 | 0.50 | 0.86 | 0.98 | 0 | 1.83 | 0 | 4493.16 |
DOX | 6 | 12 | 5 | −0.04 | −4.80 | 209.31 | 0.02 | 0.78 | 0.02 | 0 | 2.71 | 1 | 324.50 |
TMP | 0 | 2 | 0 | 0.66 | −1.51 | 22.52 | 0.93 | 0.49 | 0.99 | 0 | 1.77 | 0 | 1194.46 |
a HBD (hydrogen bond donor), b HBA (hydrogen bond acceptor), c RBN (number of rotatable bonds), d logP (log of the octanol/water partition coefficient), e log S (log of the aqueous solubility), and f PSA (polar surface area) were predicted using Discovery Studio 2.0 software. g HIA (human intestinal absorption), h PPB (plasma protein binding), I CYP3D4 (CYP3D4 inhibition), j T1/2 (half lifetime), k HT (human hepatoxicity), and l LD50 (median lethal dose) were calculated via http://admet.scbdd.com/home/index/