Table 2.
CoMSIA Results for inhibition of AZT excision by bisphosphonates
| CoMSIA pIC50 Predictions
|
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|---|---|---|---|---|---|---|---|---|---|---|
| Experimental
|
Test Sets b |
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| Compound a | IC50 (μM) | pIC50 (M) | Training Set | 1 | 2 | 3 | 4 | 5 | Pred | Residual |
| 5 | 0.5 | 6.3 | 6.1 | 6.1 | 6.1 | 6.1 | 6.2 | 6.1 | 6.1 | 0.2 |
| 6 | 0.9 | 6.1 | 5.9 | 5.9 | 5.9 | 5.8 | 5.9 | 5.9 | 5.8 | 0.2 |
| 7 | 1.0 | 6.0 | 5.6 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | 0.2 |
| 8 | 1.0 | 6.0 | 5.9 | 5.8 | 5.8 | 5.8 | 5.9 | 5.8 | 5.8 | 0.1 |
| 9 | 1.3 | 5.9 | 5.9 | 5.8 | 5.8 | 5.7 | 5.8 | 5.6 | 5.6 | 0.3 |
| 10 | 1.5 | 5.8 | 5.9 | 5.9 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | 0.0 |
| 11 | 1.9 | 5.7 | 5.9 | 5.8 | 5.7 | 5.7 | 5.8 | 5.7 | 5.8 | 0.0 |
| 12 | 2.1 | 5.7 | 5.5 | 5.6 | 5.5 | 5.6 | 5.6 | 5.6 | 5.5 | 0.1 |
| 13 | 2.2 | 5.7 | 5.5 | 5.7 | 5.7 | 5.7 | 5.6 | 5.7 | 5.7 | 0.0 |
| 14 | 2.4 | 5.6 | 5.8 | 5.6 | 5.6 | 5.6 | 5.9 | 5.6 | 5.9 | −0.3 |
| 15 | 2.9 | 5.5 | 5.4 | 5.4 | 5.4 | 5.5 | 5.7 | 5.5 | 5.5 | 0.0 |
| 3 | 3.2 | 5.5 | 5.5 | 5.7 | 5.7 | 5.6 | 5.6 | 5.6 | 5.7 | −0.2 |
| 16 | 3.3 | 5.5 | 5.6 | 5.5 | 5.6 | 5.6 | 5.6 | 5.6 | 5.6 | −0.1 |
| 17 | 3.5 | 5.5 | 5.0 | 5.1 | 5.1 | 5.2 | 5.2 | 5.2 | 5.2 | 0.3 |
| 18 | 3.9 | 5.4 | 5.4 | 5.5 | 5.4 | 5.4 | 5.4 | 5.4 | 5.4 | 0.0 |
| 19 | 3.9 | 5.4 | 5.2 | 5.2 | 5.2 | 5.2 | 5.5 | 5.2 | 5.2 | 0.2 |
| 20 | 4.6 | 5.3 | 4.7 | 4.4 | 5.5 | 5.3 | 5.3 | 5.3 | 4.4 | 0.9 |
| 21 | 5.0 | 5.3 | 5.5 | 5.6 | 5.6 | 5.5 | 5.5 | 5.5 | 5.5 | −0.2 |
| 22 | 5.2 | 5.3 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | 5.8 | −0.5 |
| 23 | 5.4 | 5.3 | 5.4 | 5.3 | 5.2 | 5.1 | 5.2 | 5.2 | 5.1 | 0.2 |
| 24 | 7.9 | 5.1 | 4.9 | 5.1 | 5.1 | 5.1 | 5.1 | 5.0 | 5.1 | 0.0 |
| 25 | 9.5 | 5.0 | 4.9 | 5.0 | 5.0 | 5.0 | 4.9 | 4.7 | 4.7 | 0.3 |
| 26 | 11 | 5.0 | 5.0 | 4.8 | 5.8 | 5.2 | 5.1 | 5.2 | 5.8 | −0.9 |
| 27 | 38 | 4.4 | 4.4 | 4.2 | 4.2 | 4.2 | 4.2 | 4.2 | 4.2 | 0.2 |
| 28 | 51 | 4.3 | 4.9 | 4.4 | 4.6 | 4.5 | 4.5 | 4.5 | 4.5 | −0.2 |
|
| ||||||||||
| 32 | 302 | 3.5 | 3.8 | 3.3 | 3.4 | 3.3 | 3.2 | 3.3 | 3.3 | 0.2 |
| 38 | 302 | 3.5 | 3.1 | 3.3 | 3.3 | 3.3 | 3.4 | 3.3 | 3.3 | 0.2 |
| 41 | 302 | 3.5 | 3.9 | 3.5 | 3.5 | 3.5 | 3.6 | 3.5 | 3.5 | 0.0 |
| 42 | 302 | 3.5 | 3.7 | 3.3 | 3.3 | 3.3 | 3.4 | 3.3 | 3.3 | 0.2 |
| 40 | 302 | 3.5 | 4.2 | 4.1 | 4.0 | 4.1 | 4.1 | 4.0 | 4.1 | −0.5 |
| 33 | 302 | 3.5 | 3.2 | 3.4 | 3.3 | 3.3 | 3.2 | 3.3 | 3.3 | 0.2 |
| 43 | 302 | 3.5 | 3.9 | 3.9 | 3.9 | 3.9 | 3.9 | 3.9 | 3.9 | −0.4 |
| 34 | 302 | 3.5 | 3.6 | 3.6 | 3.6 | 3.7 | 3.6 | 3.6 | 3.6 | −0.1 |
| 31 | 302 | 3.5 | 3.3 | 3.6 | 3.6 | 3.6 | 3.6 | 3.6 | 3.6 | −0.1 |
| 45 | 302 | 3.5 | 3.4 | 3.7 | 3.6 | 3.6 | 3.4 | 3.6 | 3.6 | 0.0 |
|
| ||||||||||
| q2 | 0.63 | 0.70 | 0.68 | 0.66 | 0.67 | 0.61 | ||||
| r2 | 0.91 | 0.96 | 0.95 | 0.95 | 0.97 | 0.95 | ||||
| F test | 73 | 115 | 108 | 107 | 151 | 110 | ||||
| N | 35 | 33 | 33 | 33 | 33 | 33 | ||||
| n | 4 | 5 | 5 | 5 | 5 | 5 | ||||
| % Steric | 0.19 | 0.19 | 0.19 | 0.19 | 0.18 | 0.18 | ||||
| % Electrostatic | 0.32 | 0.33 | 0.35 | 0.35 | 0.34 | 0.35 | ||||
| % Hydrophobic | 0.28 | 0.27 | 0.27 | 0.27 | 0.29 | 0.27 | ||||
| % Donor | 0.20 | 0.20 | 0.20 | 0.20 | 0.21 | 0.20 | ||||
|
|
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a
Structures shown in Figure 1.
b
Bold values represent predicted activities of compounds that were not included in the training set.