Table 4.
In silico physicochemical pharmacokinetic parameters important for good oral bioavailability of the synthesized compounds 7(a–l).
| Entry | M.W a | LogP o/w b (−2.0–6.5) |
n-ON c (<10) | n-OHNH d (<5) | PSA e (7–200) | 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) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 7a | 356.8 | 4.82 | 5.5 | 1 | 76.2 | 0.31 | −5.8 | 98 | 2 | −6.8 | 0 |
| 7b | 391.2 | 5.34 | 5.5 | 1 | 74.4 | 0.37 | −6.1 | 99 | 2 | −6.6 | 0 |
| 7c | 338.3 | 5.18 | 6.2 | 2 | 98.4 | 0.02 | −4.7 | 89 | 3 | −6.7 | 0 |
| 7d | 338.3 | 5.17 | 6 | 2 | 98.2 | 0.03 | −4.3 | 88 | 3 | −6.5 | 0 |
| 7e | 368.4 | 5.27 | 7.2 | 1 | 133.3 | −0.04 | −4.7 | 75 | 3 | −6.6 | 0 |
| 7f | 382.4 | 5.09 | 7 | 2 | 105.7 | 0.16 | −5.5 | 91 | 4 | −6.9 | 0 |
| 7g | 352.4 | 4.91 | 6.2 | 1 | 83.9 | 0.16 | −5.1 | 100 | 3 | −6.7 | 0 |
| 7h | 382.4 | 5.20 | 7 | 1 | 89.0 | 0.19 | −5.4 | 100 | 4 | −6.7 | 0 |
| 7i | 412.2 | 4.05 | 7.7 | 1 | 95.4 | 0.17 | −5.4 | 100 | 5 | −6.5 | 0 |
| 7j | 412.2 | 4.08 | 7.7 | 1 | 97.6 | 0.19 | −5.6 | 100 | 5 | −6.6 | 0 |
| 7k | 312.3 | 3.91 | 6 | 1 | 84.7 | −0.11 | −4.0 | 94 | 3 | −6.3 | 0 |
| 7l | 328.4 | 4.11 | 5 | 1 | 85.6 | −0.21 | −4.2 | 95 | 3 | −6.2 | 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 of human oral absorption (% ABS) (>80% is high, <25% is poor); #Metabolism I (1–8); j Predicted IC50 value for blockage of HERG K+ channels (log Khsa) (−1.5 to 1.2).