Table 1. Docking scores and physico-chemical properties of hit and reference compounds.
Compound ranking (Glide Gscore (kcal/mol)) and calculated properties of the top twenty hits (1-20) and reference compounds (A-F).
| Cmpd | Glide Gscore | Set | Source Idx | Series | Bnd Mode | BBB score | logS (7.4) | Mw | cLogP | HBD | HBA | Lipinski | NHOH | RotB | TPSA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | −12.1 | DIV | 29267 | 1 | I | 4.2 | −5.2 | 293.33 | 3.2 | 2 | 4 | Y | 2 | 4 | 67 |
| 2 | −11.5 | DIV | 2147 | 2 | I | 4.1 | −3.3 | 279.34 | 0.7 | 2 | 4 | Y | 2 | 5 | 84 |
| 3 | −10.8 | DIV | 37503 | 2 | I | 3.9 | −4.2 | 342.4 | 0.7 | 1 | 6 | Y | 1 | 4 | 95 |
| 4 | −10.4 | DIV | 41088 | 1 | I | 2.7 | −5.0 | 364.41 | 2.1 | 2 | 7 | Y | 2 | 4 | 96 |
| 5 | −10.3 | DIV | 45423 | 1 | I | 2.7 | −5.2 | 378.44 | 2.9 | 2 | 7 | Y | 2 | 5 | 96 |
| 6 | −10.3 | DIV | 42130 | 2 | I | 4.3 | −2.5 | 329.4 | 1.5 | 1 | 5 | Y | 1 | 6 | 92 |
| 7 | −9.8 | DIV | 8757 | 3 | I | 3.2 | −1.7 | 218.22 | 0.9 | 2 | 5 | Y | 2 | 3 | 80 |
| 8 | −9.7 | DIV | 8892 | 3 | I | 3.0 | −1.5 | 204.19 | 0.6 | 3 | 5 | Y | 3 | 2 | 91 |
| 9 | −9.2 | DIV | 9167 | 4 | II | 3.4 | −2.3 | 250.26 | 0.0 | 2 | 5 | Y | 2 | 4 | 95 |
| 10 | −11.3 | NC1 | 15860 | 6 | I | 1.9 | 0.0 | 209.17 | −0.9 | 4 | 5 | Y | 4 | 3 | 124 |
| 11 | −11.0 | NC1 | 34346 | 1 | I | 3.4 | 0.6 | 231.21 | 0.5 | 2 | 4 | Y | 2 | 3 | 96 |
| 12 | −10.9 | NC1 | 21399 | 5 | I | 3.7 | −2.3 | 347.37 | −0.9 | 2 | 5 | Y | 2 | 4 | 99 |
| 13 | −10.7 | NC1 | 36469 | 9 | I | na | na | 358.35 | 2.4 | 5 | 6 | Y | 5 | 7 | 135 |
| 14 | −9.8 | NC2 | 13787 | 7 | II | na | na | 312.27 | −0.1 | 5 | 7 | Y | 5 | 6 | 145 |
| 15 | −9.6 | NC2 | 7454 | 5 | I | 4.6 | 0.6 | 222.29 | 0.4 | 2 | 3 | Y | 2 | 2 | 56 |
| 16 | −9.6 | NC1 | 16482 | 9 | II | na | na | 453.46 | 0.2 | 5 | 5 | Y | 6 | 8 | 171 |
| 17 | −9.4 | NC2 | 13777 | 7 | II c | na | na | 312.23 | −0.4 | 5 | 7 | Y | 5 | 6 | 162 |
| 18 | −9.1 | NC2 | 13788 | 7 | II c | na | na | 312.27 | −0.1 | 5 | 7 | Y | 5 | 6 | 145 |
| 19 | −8.6 | NC2 | 15222 | 8 | II c | na | na | 396.44 | 0.6 | 4 | 5 | Y | 6 | 13 | 176 |
| 20 | −8.4 | NC2 | 15223 | 8 | II | na | na | 396.44 | 0.6 | 4 | 5 | Y | 6 | 13 | 176 |
| A | −6.4 | Ref 63 | EG00229 | 10 | II c | na | na | 497.58 | 0.8 | 5 | 9 | Y | 7 | 10 | 203 |
| B | −5.8 | Ref 70 | EG01377 | 10 | II | na | na | 586.7 | 1.8 | 6 | 8 | N | 9 | 12 | 212 |
| C | −5.2 | Ref 65 | 1 | 11 | II c | 3.2 | −7.9 | 444.52 | 4.4 | 3 | 5 | Y | 3 | 3 | 88 |
| D | −4.3 | Ref 64 | 32 | 12 | II | na | na | 500.6 | 0.0 | 6 | 6 | Y | 9 | 10 | 190 |
| E | −4.1 | Ref 67 | CB-7739526 | 13 | na | 5.0 | −3.5 | 390.69 | 4.3 | 2 | 4 | Y | 2 | 8 | 51 |
| F | −3.5 | Ref 68 | NRPa-308 | 14 | II | 4.1 | −6.2 | 424.52 | 4.8 | 2 | 4 | Y | 2 | 7 | 85 |
Set: screening library; Source Idx: reference to internal ID in the screening set; Series: chemotype assignment to hit series 1-9 and known compound series 10-14; Bnd Mode: binding Mode I or II (c denotes use of constrained docking); BBB score: score for compound probability of having CNS exposure; LogS(7.4) predicted solubility (M) at pH 7.4; Mw molecular weight (Da); cLogP predicted lipophilicity coefficient in octanol/water; HBD number of hydrogen-bond donors; HBA number of hydrogen bond acceptors; Lipinski - a binary (Y/N) assignment of complying with Lipinski rule-of-5; NHOH number of polar NH and OH hydrogens; RotB number of rotatable bonds; TPSA total polar surface area (Å2); na denotes not applicable.
Properties were calculated using RDKit and ChemAxon Aqueous solubility module.