Drug Discovery Filtering

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Simple structure based filters are integrated into JChem for Excel useful in the early phase of drug discovery to eliminate those compounds, which will probably fall out on screening tests. These filters in general return TRUE, if a structure satisfies all filtering criteria, FALSE otherwise.

 

The function names and filtering criteria are the following:

 

JCLipinskiRuleof53of4

Returns TRUE if the molecule passes 3 of the following 4 criteria:

Molweight: <= 500

LogP <= 5

Number of H-Donor atoms <= 5; Number of H-Acceptor atoms <= 10

 

JCLipinskiRuleof54of4

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

 

JCLeadLikeness

When designing leadlike combinatorial libraries, care should be exercised not

to 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.

 

JCGhoseFilter

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.

 

JCMueggeFilter

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

PSA <= 150

 

JCVeberFilter

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.

 

JCBioavailability

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 different: if at least 6 from these criteria are TRUE for a molecule, then JCBioavailability returns TRUE, otherwise FALSE.


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