Table 2.
ADME-T properties of compounds MA69, MA120, and MA152, predicted by QikProp, Schrodinger.
| S. No. | Property | Description | Range for orally active non-CNS drugs |
Compound MA69 | Compound MA120 | Compound MA152 | |||
|---|---|---|---|---|---|---|---|---|---|
| QL | PL | PU | QU | ||||||
| 1 | #stars | drug likeness penalty; the higher the value, the less drug-like the molecule | 0 | 0 | 0 | 8 | 0 | 0 | 0 |
| 2 | #amine | no. of basic amines | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| 3 | #amidine | no. of amidines groups | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 4 | #acid | no. of carboxylic acid groups | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| 5 | #amide | no. of amides groups | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| 6 | #rotor | no. of rotatable bonds (without CX3, alkene, amide, small ring) | 0 | 2 | 6 | 17 | 6 | 5 | 5 |
| 7 | CNS | a qualitative CNS activity parameter | −2 | −2 | −1 | 1 | −1 | −2 | 0 |
| 8 | dipole | computed dipole moment | 0.96 | 3.7 | 7.7 | 12 | 3.56 | 7.46 | 6.25 |
| 9 | SASA | solvent accessible surface area | 265 | 459 | 660 | 1023 | 680.74 | 745.25 | 614 |
| 10 | FOSA | SASA on saturated carbon and attached hydrogen | 0 | 69 | 304 | 667 | 253.67 | 220.52 | 124.89 |
| 11 | FISA | SASA on N, O, and H attached to heteroatoms | 0 | 81 | 176 | 306 | 111.08 | 169.13 | 92.77 |
| 12 | PISA | π component of SASA | 0 | 0 | 138 | 371 | 314.13 | 353.73 | 396.34 |
| 13 | WPSA | weakly polar component of the SASA (halogens, P, and S) | 0 | 0 | 0 | 144 | 1.85 | 1.86 | 0 |
| 14 | volume | solvent accessible volume (Å3) | 410 | 763 | 1178 | 2082 | 1211.06 | 1306.56 | 1050.95 |
| 15 | donorHB | estimated no. of hydrogen bonds that would be donated to the solvent water | 0 | 1 | 2.5 | 5 | 1.5 | 2.5 | 1.5 |
| 16 | accptHB | estimated no. of hydrogen bonds that would be accepted from the solvent water | 0 | 4 | 8.2 | 16.1 | 7.5 | 9 | 4.5 |
| 17 | glob | a globularity descriptor (1 for a sphere) | 0.73 | 0.81 | 0.88 | 0.94 | 0.80 | 0.77 | 0.81 |
| 18 | QPpolrz | predicted polarizability (Å3) | 10 | 25 | 41 | 71 | 41.46 | 46.30 | 36.48 |
| 19 | QPlogPo/w | octanol−water logP | −2.6 | 0.76 | 4 | 7.3 | 3.29 | 2.78 | 3.73 |
| 20 | QPlogS | solubility in log(moles/l) | −9.4 | −4.9 | −2.3 | 0.47 | −4.96 | −5.72 | −4.97 |
| 21 | CIQPlogS | log of conformation-independent solubility | −9.6 | −5.1 | −2.4 | 0.14 | −4.69 | −5.11 | −4.80 |
| 22 | QPPCaco | apparent Caco-2 cell permeability | 0 | 0 | 198 | 3975 | 875.98 | 246.62 | 1306.45 |
| 23 | QPlogBB | brain/blood partition coefficient | −3.1 | −1.5 | −0.36 | 0.78 | −0.93 | −1.60 | −0.67 |
| 24 | QPPMDCK | predicted apparent MDCK cell permeability (nm/s) | 0 | 0 | 133 | 5302 | 438.88 | 111.54 | 660.44 |
| 25 | QPlogKhsa | prediction of binding to human serum albumin | −1.80 | −0.67 | 0.24 | 1.42 | 0.18 | 0.15 | 0.36 |
| 26 | HumanOralAbsorption | Human oral absorption | 1 | 3 | 3 | 3 | 3 | 3 | 3 |
| 27 | PercentHumanOralAbsorption | Percent of human oral absorption | 10 | 77 | 100 | 100 | 100 | 86 | 100 |
| 28 | PSA | van der Waals surface area of polar nitrogen and oxygen atoms | 0 | 61 | 120 | 194 | 75.12 | 106.51 | 75.20 |
| 29 | #NandO | no. of N and O atoms | 0 | 3 | 6 | 13 | 5 | 7 | 5 |
| 30 | RuleOfFive | no. of violations of Lipinski's rule of five | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| 31 | RuleOfThree | no. of violations of Jorgensen's rule of three | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| 32 | #in34 | no. of atoms in three- or four-membered rings | 0 | 0 | 0 | 4 | 0 | 0 | 0 |
| 33 | #in56 | no. of atoms in five- or six-membered rings | 0 | 9 | 16 | 24 | 16 | 21 | 16 |
| 34 | #noncon | no. of atoms not able to form conjugation in nonaromatic rings | 0 | 0 | 2 | 14 | 4 | 5 | 0 |
| 35 | #nonHatm | no. of non-H atoms | 4 | 17 | 27 | 46 | 27 | 30 | 24 |
Abbreviations: QL, qualifying lower limit; PL, preferred lower limit; QU, qualifying upper limit; PU, preferred upper limit [QL, PL, QU and PU values for non-CNS drug criteria were taken from [64]].