FAFDrugs4
| Descriptor | Denomination | Minimum Parameter | Maximum Parameter |
|---|---|---|---|
| Molecular Weight | MW | inf_mw | sup_mw |
| Molecular weight or molar mass | |||
| logP | logP | inf_logp | sup_logp |
| The logarithm of the partition coefficient between n-octanol and water, characterizing lipophilicity. XLOGP3 and OpenBabel methods were benchmarked on a set of 1300 molecules with experimental logP values from US National Cancer Institute, showing that XLOGP3 (r2=0.94) give a better prediction accuracy. Lipinski RO5 stands on CLOGP values, but Mannhold et al. benchmarked several models and showed that XLOGP3 and CLOGP methods give similar results [46] |
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| logD | logD | - | - |
| The logD represents the logP of compounds at physiological pH (7.4) | |||
| logSw | logSw | - | - |
| The logSw represents the logarithm of compounds water solubility computed by the ESOL method [45] | |||
| topological Polar Surface Area | tPSA | inf_psa | sup_psa |
| summation of tabulated surface contributions of polar fragments (i.e. atoms regarding also their bonding pattern) | |||
| Hydrogen Bond Donnors | HBD | inf_hbd | sup_hbd |
| sum of all OHs and NHs (according to Lipinski RO5 definition) | |||
| Hydrogen Bond Acceptors | HBA | inf_hba | sup_hba |
| sum of all O and N (according to Lipinski RO5 definition) | |||
| Hydrogen Bond Donnors and Acceptors |
HBonds | inf_hba | sup_hba |
| sum of Hydrogen Bond Donnors and Acceptors Note: only involved in the "respirtory" filter according to Ritchie et al. [25] |
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| Number of SSSR | n_SystemRing | inf_nc | sup_nc |
| The Smallest Set of Smallest Rings (SSSR) is the smallest ring building blocks necessary to form otherring systems (e.g. 3 for a compound involving 3 phenyl) | |||
| Size of the Biggest System Ring |
MaxSizeSystemRing | - | max_ring |
| Number of atoms involved in the biggest system ring (e.g. 12 for 2 fused 6 membered-ring) | |||
| Number of Rotatable Bonds | RotatableBonds | inf_nbb | sup_nbb |
| Number of any single non-ring bond, bounded to nonterminal heavy (i.e., non-hydrogen) atom. Amide C-N bonds are not considered because of their high rotational energy barrier, as decribed by Veber et al. [41] . |
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| Number of Rigid Bonds | RigidBonds | inf_nrb | sup_nrb |
| Number of non-flexible bonds, in opposite to rotatable bonds (e.g. double and triple bonds, bonds involved in ring systems and additionnaly amide bonds) | |||
| Number of Charged Groups | NumCharges | inf_cf | sup_cf |
| Number of Charged Groups (e.g. 1 for a compound with a carboxylic acid group) |
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| Compound Total Charge | TotalCharge | inf_sc | sup_sc |
| Formal total charge of the compound. (e.g. -1 for a compound with a carboxylic acid group) |
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| Number of Carbon Atoms | n_carbon | inf_c | sup_c |
| Number of carbon atom | |||
| Number of Heteroatoms | n_hetero | inf_h | sup_h |
| Number of non carbon atoms (hydrogens are not included) | |||
| Number of Heavy Atoms | inf_hva | sup_hva | |
| Number of non hydrogens atoms | |||
| het/carbon atoms ratio | ratioH_C | inf_r | sup_r |
| The ratio between the number of non carbon atoms and the number of carbon atoms. | |||
| Number of Rule-of-5 Violations | n_LipinskiViolations | - | max_lipinski |
| Rule of thumb according to Lipinski et al [13] stating on that 4 properties: MW ≤ 500; H-Bonds Donors ≤ 5 ; H-Bonds Acceptors ≤ 10 ; logP ≤ 5 If two properties are out of range, a poor absorption or permeability is possible, one is acceptable. |
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| Solubility | Solubility | - | - |
| Water Solubility mg/l estimated by ESOL method [45] | |||
| Solubility Forecast Index | Solubility Forecast Index | - | - |
| Water Solubility estimated by Hill et al method [77] | |||
| Veber Rule | VeberRule | - | - |
| Bad or Good oral biovailability rule, according to Veber et al [41] stating on: (rotatable bonds ≤10) and (tPSA ≤ 140 Å or H-Bonds Donors+H-Bonds Acceptors ≤ 12) |
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| Egan Rule | EganRule | - | - |
| Bad or Good oral biovailability rule, according to Egan et al. [40] stating on: ( 0 ≥ tPSA ≤ 132 ) and ( -1 ≥ logP ≤ 6) |
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| Oral PhysChem Score | TrafficLights | - | - |
| An Oral PhysChem Score extensively used at Bayer according to Lobell et al. [38] | |||
| GSK 4/400 | GSK 4/400 | - | - |
| Rule which relates to compounds with a logP less than 4 and a MW less than 400 Da may have a more favourable ADMET profile [26] | |||
| Pfizer 3/75 | Pfizer 3/75 | - | - |
| Rule which relates to compounds with a high log P (>3) and low TPSA (<75) are approximately 2.5 times more likely to be toxic as to be clean [54] | |||
| Fsp3 | Fsp3 | - | - |
| According to Lovering et al. [39], Fsp3 (carbon bond saturation) is defined as the number of sp3 hybridized carbons / total carbon count. This descriptor could correlates with melting point and solubility. | |||
| Number of Stereocenters | StereoCenters | - | - |
| According to Lovering et al. [39], the presence of stereo centers (also, number of chiral centers), is a descriptor of complexity which also increases from discovery through clinical trials, to drugs | |||
| Compound Final Status | State | - | - |
| Compound state after all rules applied (i.e. Accepted, Intermediate or Rejected) | |||