Details of physico-chemical property filters available in FAF-Drugs4


 Rule of 3    Rule of 5    Drug-Like Soft 1   Lead-Like Soft 2     R.E.O.S       ZINC         CNS         Respiratory   
MW ≤ 300 (≤ 500) 100 - 600 150 - 400 200 - 500 60 - 600 135 - 582 240 - 520
logP -3 to 3 (≤ 5) -3 to 6 -3 to 4 -5 to 5 -4 to 6 -0.2 to 6.1 -2 to 4.7
HBA ≤ 3 (≤ 10) ≤ 12 ≤ 7 ≤ 10 ≤ 11 ≤ 5 -
HBD ≤ 3 (≤ 5) ≤ 7 ≤ 4 ≤ 5 ≤ 6 ≤ 3 -
HBonds - - - - - - - 6 - 12
tPSA ≤ 60 - ≤ 180 ≤ 160 ≤ 150 ≤ 150 3 - 118 51 - 135
Rotatable Bonds ≤ 3 - ≤ 11 ≤ 9 ≤ 8 ≤ 12 - 3 - 8
Rigid Bonds - - ≤ 30 ≤ 30 ≤ 50
Rings - - ≤ 6 ≤ 4 - ≤ 7 - 1 - 5
MaxSizeSystemRing - - ≤ 18 ≤ 18 - ≤ 12 - -
Carbons - - 3 - 35 3 - 35 - ≥ 3 - -
HeteroAtoms - - 1 - 15 1 - 15 - ≥ 0 - -
H/C Ratio - - 0.1 to 1.1 0.1 to 1.1 ≤ 2.0 - -
Charges - - ≤ 4 ≤ 4 - ≤ 4 - -
TotalCharge - - -4 to 4 -4 to 4 -4 to 4 -4 to 4 - -
RO5 Violations - 2 - - - - - -
StereoCenters - - - ≤ 2 - - - -
References 35 13 13,19,24,30,49 30,32,47,48 34 24 36 25
1. We designed the Drug-Like Soft filter by combining several articles describing drugs' physico-chemical properties (13,19,24,30) and an in-house statistical analysis of drugs. Indeed, an analysis of the descriptors values of 916 FDA oral drugs (computed by FAF-Drugs4) extracted from the e-Drugs3D library (49), allows us to define a chemical space comprising up to 90% of these oral drugs and to propose the filter thresholds.
The reasons why some compounds do not fit in our oral chemical space are mostly due to a high Molecular Weight (see below Rinfampin) or because of a high hydrophobicity (see Probucol), but also too many Rotatable Bonds (see Aliskerin) or too many H-Bonds Donors (see Kanamycin).



Rinfampin (MW: 823 Da)

 Pentosan Polysulphate (logP: 11.33 )



Aliskerin (RotBonds: 18)



Kanamycin (HBD: 15)
NB: applying that filter on the March 2013 ChemBridge Express-Pick Collection Stock eliminates 5.1% of the molecules.

2. The Lead-Like Soft filter takes into articles (30,32,47,48) describing leads' physico-chemical properties and lead-like filtering (red values) combined with the Drug-Like Soft filter. The goal is is to have starting point molecules after screening that have the potential to be optimized (e.g., relatively small with a relatively small log P and thus molecules that could be decorated further to increase affinity and or selectivity without becoming very ADMET unfriendly).