The simple structure-based filters integrated into JChem for Office are useful in the early phase of drug discovery to eliminate compounds, which will probably fall out on screening tests. These filters in general return TRUE, if a structure satisfies all filtering criteria.
The property names and filtering criteria are as follows:
Returns TRUE if the molecule passes 3 of the following 4 criteria:
Returns TRUE if the molecule passes all of the following 4 criteria:
Molweight ≤ 500
LogP ≤ 5
Number of H-Donor atoms ≤ 5
Number of H-Acceptor atoms ≤ 10
Reference: Lipinski C.A.; et al; Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. ; Adv. Drug. Del. Rev.; 2001; 46, 3–26.
When designing leadlike combinatorial libraries, do not exceed the following property values:
Molweight: ≤ 450
LogD (on pH 7.4) ≥ -4 and ≤ 4
Number of Rings: ≤ 4
Number of Rotatable Bonds ≤ 10
Number of H-Donor atoms ≤ 5
Number of H-Acceptor atoms ≤ 8
Reference: Oprea, T.I. et al.; Is There a Difference between Leads and Drugs? A Historical Perspective ; J. Chem. Inf. Comput. Sci., 2001, 41, 1308-1315.
Molweight ≥ 160 and ≤ 480
Number of Atoms ≥ 20 and ≤ 70
LogP between -0.4 and 5.6
Refractivity ≥ 40 and ≤ 130
Reference: Ghose, A. K. et al., A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases . J. Comb. Chem., 1999, 1(1), 55-68.
Molweight ≥ 200 and ≤ 600
Number of Rings ≤ 7
Number of C Atoms ≥ 5 and (Number of Atoms-Number of C Atoms-Number of H Atoms) ≥ 2
Number of Rotatable Bonds ≤15
Number of H-Donor atoms ≤ 5
Number of H-Acceptor atoms ≤ 10
LogP ≥ -2 and ≤ 5
Compounds, which meet only these two criteria will have a high probability of good oral bioavailability in the rat:
Number of Rotatable Bonds < 12
Polar Surface Area < 140 A²
Reference: Veber, Daniel F. et al; Molecular Properties That Influence the Oral Bioavailability of Drug Candidates, J. Med. Chem., 2002, 45(12), 2615-2623.
Molweight ≤ 500
LogP ≤ 5
Number of H-Donor atoms ≤ 5
Number of H-Acceptor atoms ≤ 10
Number of Rotatable Bonds ≤ 10
Polar Surface Area ≤ 200
Number of Fused Aromatic Rings ≤ 5
This function works slightly differently if at least six from these criteria are TRUE for a molecule, then JCBioavailability returns TRUE, otherwise FALSE.