Table 1.
ADME and toxicity profile of the selected favipiravir's derivatives.
Properties | L1 | L2 | L3 | L4 | L5 | L6 | L7 | F |
---|---|---|---|---|---|---|---|---|
Num. rotatable bonds | 02 | 02 | 02 | 02 | 02 | 02 | 02 | 01 |
Num. H-bond acceptors | 05 | 04 | 05 | 04 | 04 | 04 | 09 | 05 |
Num. H-bond donors | 02 | 03 | 03 | 02 | 02 | 02 | 02 | 02 |
Fraction Csp3 | 0.00 | 0.00 | 0.00 | 0.00 | 0.55 | 0.50 | 0.55 | 0.00 |
TPSA (A2) |
101.99 |
104.89 |
117.78 |
117.34 |
89.10 |
89.10 |
89.10 |
89.10 |
Log Po/w | 0.17 | 0.04 | −0.40 | 0.86 | 1.23 | 0.89 | 1.52 | −0.16 |
Log S |
−1.67 |
−1.52 |
−1.12 |
−2.16 |
−2.44 |
−2.03 |
−2.76 |
−1.13 |
GI absorption | High | High | High | High | High | High | High | High |
BBB permeant | No | No | No | No | No | No | No | No |
P-gb substrate | No | No | No | No | No | No | No | No |
CYP1A2 | Yes | No | No | No | No | No | No | No |
CYP2C19 | No | No | No | No | No | No | No | No |
CYP2C9 | No | No | No | No | No | No | No | No |
CYP2D6 | No | No | No | No | No | No | No | No |
Log Kp (cms−1) |
−7.54 |
−7.54 |
−8.01 |
−7.04 |
−6.43 |
−6.73 |
−7.18 |
−7.29 |
Lipinski's rules | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
BS |
0.55 |
0.55 |
0.55 |
0.55 |
0.55 |
0.55 |
0.55 |
0.55 |
PAINS (alert) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Brenk (alert) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Synthetic accessibility |
2.44 |
2.59 |
2.45 |
2.54 |
2.65 |
2.54 |
4.15 |
2.03 |
Hepatotoxicity | Slightly active | Slightly active | Slightly active | Slightly active | Inactive | Inactive | Inactive | Inactive |
Carcino | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive |
Immuno | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive |
Mutagenicity | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive |
Cytotoxicity | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive | Inactive |
LD50 (mg kg−1) | 575 | 1000 | 2000 | 800 | 1356 | 1356 | 2000 |
Total polar surface area (TPSA), Consensus Log Po/w (lipophilicity), Log Kp (skin permeation), Log S (ESOL) (water solubility), GI (gastrointestinal absorption), BBB (blood brain barrier), P-gb (p-glycoprotein), BS (bioavailability score), Inhibitors (CYP1A2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4), Carcino (Carcinogenicity), Immuno (Immunotoxicity), LD50 (lethal dose 50 %)