Table 3.
In silico physicochemical pharmacokinetic parameters important for good oral bioavailability of the synthesized compounds 4a–o.
| Entry | M.W a | Log Po/w b (−2.0 to 6.5) | n-ON c (<10) | n-OHNH d (<5) | PSA e (7–200.0) | Log Khsa f (−1.5–1.2) | Log S g (−6–0.5) | % ABS h | # Meta i (1–8) | Log HERG j (below −5) | Lipinski Rule of 5 (≤1) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 4a | 431.5 | 4.9 | 5.2 | 1 | 51.7 | 0.9 | −4.7 | 100 | 4 | −6.1 | 0 |
| 4b | 466.0 | 5.5 | 5.2 | 1 | 48.5 | 1.1 | −5.5 | 100 | 3 | −6.1 | 0 |
| 4c | 498.1 | 5.2 | 5.2 | 1 | 48.9 | 1.0 | −5.0 | 100 | 3 | −6.0 | 0 |
| 4d | 449.5 | 5.2 | 5.2 | 1 | 48.6 | 1.0 | −5.1 | 100 | 3 | −6.1 | 0 |
| 4e | 467.5 | 5.2 | 5.2 | 1 | 50.7 | 1.0 | −4.9 | 96.9 | 4 | −6.0 | 0 |
| 4f | 461.6 | 5.0 | 6.0 | 1 | 58.9 | 0.9 | −4.7 | 95.9 | 4 | −6.1 | 0 |
| 4g | 491.6 | 5.2 | 6.7 | 1 | 64.5 | 1.0 | −5.2 | 100 | 4 | −6.2 | 0 |
| 4h | 521.0 | 5.3 | 7.5 | 1 | 69.6 | 1.0 | −5.3 | 84.9 | 6 | −6.1 | 0 |
| 4i | 447.5 | 4.2 | 6 | 1 | 71.8 | 0.8 | −4.6 | 95.0 | 4 | −6.2 | 0 |
| 4j | 447.5 | 4.1 | 6 | 1 | 70.9 | 0.8 | −4.6 | 95.0 | 4 | −6.2 | 0 |
| 4k | 478.2 | 4.2 | 6 | 1 | 71.8 | 0.9 | −4.7 | 95.0 | 4 | −6.0 | 0 |
| 4l | 490.2 | 4.1 | 6 | 1 | 50.7 | 1.0 | −5.1 | 96.9 | 4 | −6.0 | 0 |
| 4m | 432.5 | 4.4 | 6.2 | 1 | 62.0 | 0.7 | −4.4 | 100 | 5 | −6.2 | 0 |
| 4n | 437.5 | 4.8 | 5.2 | 1 | 47.7 | 0.8 | −4.6 | 100 | 4 | −6.0 | 0 |
| 4o | 421.5 | 4.4 | 5.7 | 1 | 53.5 | 0.7 | −4.3 | 100 | 4 | −6.1 | 0 |
a Molecular weight of the molecule; b Predicted octanol–water partition coefficient (log Po/w) (–2.0 to 6.5); c n-ON number of hydrogen bond acceptors ≤10; d n-OHNH number of hydrogen bonds donors ≤5; e Polar surface area (PSA) (7.0–200.0); f Logarithm of predicted binding constant to human serum albumin (log Khsa) (−1.5 to 1.2); g Logarithm of Aqueous solubility(Log S) (−6 to 0.5); h Percentage human oral absorption (% ABS) (>80% is high, <25% is poor); i Metabolism (1–8); j Predicted IC50 value for blockage of HERG K+ channels (Log HERG) (below −5).