Table 6.
Physicochemical Drug-Like Properties of the 31 A3AR Agonists
| Ligand | LogP | MW | H-Bond Donors | H-Bond Acceptors | Rotatable Bonds | Rings | Lipinski | Lead-Like | Aqueous Solubility |
|---|---|---|---|---|---|---|---|---|---|
| MRS5698 | 3.09 | 565.0 | 4 | 9 | 7 | 6 | 1 | 1 | 0.007 |
| 2-Chloroadenosine | −0.47 | 301.7 | 5 | 9 | 2 | 3 | 0 | 0 | 0.55 |
| 2′-Me-CCPA | 1.87 | 383.8 | 4 | 9 | 4 | 4 | 0 | 0 | 0.27 |
| TCPA | 1.09 | 497.5 | 6 | 14 | 7 | 6 | 2 | 3 | 0.52 |
| NECA | −0.83 | 308.3 | 5 | 10 | 3 | 3 | 0 | 1 | 19.1 |
| MRE3008F20 | 2.26 | 423.4 | 2 | 11 | 6 | 5 | 1 | 1 | 0.38 |
| 2-Phenylethylyl-adenosine derivative | 1.1 | 408.4 | 4 | 10 | 5 | 4 | 0 | 1 | 0.35 |
| Adenosine | −0.98 | 267.2 | 5 | 9 | 2 | 3 | 0 | 0 | 1.62 |
| GS9667 | 1.44 | 361.4 | 4 | 9 | 7 | 3 | 0 | 0 | 0.08 |
| Binodenoson | 0.33 | 391.4 | 6 | 11 | 5 | 4 | 2 | 2 | 0.39 |
| (R,S)-PHPNECA | −0.47 | 301.7 | 5 | 9 | 2 | 3 | 0 | 0 | 0.55 |
| N(6)-cyclohexyladenosine | 1.29 | 349.4 | 4 | 9 | 4 | 4 | 0 | 0 | 0.73 |
| HEMADO | 1.44 | 361.4 | 4 | 9 | 7 | 3 | 0 | 0 | 0.08 |
| Cl-IB-MECA | 2.36 | 544.7 | 4 | 10 | 5 | 4 | 1 | 2 | 0.1 |
| Regadenoson | −1.82 | 390.4 | 6 | 13 | 4 | 4 | 2 | 2 | 5.27 |
| Piclidenoson | 1.69 | 510.3 | 4 | 10 | 5 | 4 | 1 | 2 | 0.56 |
| Cyclopentyladenosine | 0.88 | 355.4 | 4 | 9 | 4 | 4 | 0 | 0 | 1.19 |
| PENECA | 0.66 | 408.4 | 5 | 10 | 5 | 4 | 0 | 1 | 0.19 |
| BAY60-6583 | 2.43 | 379.4 | 4 | 7 | 9 | 3 | 0 | 0 | 0.004 |
| AB-MECA | 0.98 | 498.3 | 6 | 10 | 5 | 4 | 1 | 3 | 0.29 |
| MPC-MECA | 0.91 | 428.3 | 4 | 11 | 7 | 4 | 1 | 1 | 2.52 |
| MRS3558 | 1.86 | 463.3 | 4 | 9 | 5 | 5 | 0 | 1 | 0.05 |
| 2-Hexynyl-NECA | 0.56 | 388.4 | 5 | 10 | 7 | 3 | 0 | 1 | 0.23 |
| Apadenoson | 1.08 | 486.5 | 5 | 12 | 8 | 4 | 1 | 2 | 0.21 |
| CCPA | 1.65 | 369.8 | 4 | 9 | 4 | 4 | 0 | 0 | 0.28 |
| (S)-PIA | 1.95 | 385.4 | 4 | 9 | 6 | 4 | 0 | 0 | 0.09 |
| CP608,039 | 1.95 | 385.4 | 4 | 9 | 6 | 4 | 0 | 0 | 0.09 |
| CGS21680 | 0.69 | 499.5 | 7 | 13 | 10 | 4 | 2 | 3 | 15.1 |
| MRS5151 | −0.83 | 308.3 | 5 | 10 | 3 | 3 | 0 | 1 | 19.1 |
| I-ABA | 1.29 | 349.4 | 4 | 9 | 4 | 4 | 0 | 0 | 0.73 |
| (R)-PIA | 1.95 | 385.4 | 4 | 9 | 6 | 4 | 0 | 0 | 0.09 |
Log P represents octanol–water partition coefficient under standard conditions at 25°C (values for optimal drug-like properties are −1.00 to 4.20). MW indicates molecular weight (optimal values are ≤460.00). Optimal numbers of H-bond donors, H-bond acceptors, rotatable bonds, and rings are ≤5, ≤10, ≤10, and <4, respectively. Optimal numbers of violations for both Lipinski and lead-like are <1. Aqueous solubility was calculated at pH 6.4 and in mg/ml (≤0.01 indicates highly insoluble; 0.01–0.1, insoluble; and >0.1, soluble).