Table 1.
Essential filters for efficient library design in medicinal chemistry.
| Name | Features/Cutoffs | Developer/ Reference |
|---|---|---|
| PAINS | Removal of frequent hitters (promiscuous compounds) in HTS assays | Cancer Therapeutics-CRC P/L [64] |
| REOS | Set of rules and of functional group filters for the removal of problematic structures dubbed REOS (Rapid elimination of swill) Maintaining compounds using the following cutoffs: H-bond donor ≤ 5, H-bond acceptors ≤ 10, −2 ≤ formal charge ≤ +2, number of rotatable bonds ≤ 8, 200 ≤ Molecular weight ≤ 500, 20 ≤ number of heavy atoms ≤ 50, −2 ≤ logP ≤ 5 |
Vertex [65,66] |
| Aggregators | Tanimoto coefficient similarity search to a database of known aggregators | Irwin et al. [52] |
| Ely Lilly rules | Hybrid method of physiochemical and functional group filters for identification of promiscuous compounds | Bruns at Ely Lilly [67] |
| Lipinski (Rule of 5) | A set of rules for drug-likeness: Molecular Weight ≤ 500, logP ≤ 5, H-bond donors ≤ 5, H-bond acceptors ≤ 10 |
Lipinski at Pfizer [46] |
| Rule of 3 | A set of cutoff rules for lead-like discovery: Molecular Weight ≤ 300, logP ≤ 3, H-bond donor ≤ 3, H-bond acceptors ≤ 3 |
Congreve et al. [68] |
| Rule of 4 | A set of rules derived from protein–protein interaction inhibitors: Molecular Weight ≥ 400, logP ≥ 4, number of rings ≥ 4, H-bond acceptors ≥ 4 |
Morelli [69] |
| Oprea Lead-like and drug-like | A set of rules based on the lead-like vs. drug-like comparison: Molecular Weight < 450, −3.5 ≤ logP < 4.5, −4 ≤ logD ≤ 4, number of rings ≤ 4, nonterminal single bonds ≤ 10, H-bond donor ≤ 5, H-bond acceptor ≤ 8 |
Oprea group [70] |
| Ghose | A set of rules for drug-likeness with cutoffs: 180 ≤ Molecular Weight ≤ 480, 40 ≤ molecular refractivity ≤ 130, −0.4 ≤ logP ≤ 5.6, 20 ≤ number of atoms ≤ 70 |
Ghose et al. [71] |
| Veber | Two rules to meet the criteria for drug-likeness: rotatable bonds ≤ 10, Polar Surface Area ≤ 140 Å2 |
Veber et al [72] |
| Lee | Physiochemical properties of highly-drug like molecules: Mean Molecular Weight = 356 Mean logP = 2.1 |
Lee at Hoffman-La Roche [73] |
| van de Waterbeemd | Physiochemical properties for permeability and blood brain barrier permeability: Molecular Weight ≤ 450, Polar Surface Area ≤ 90 Å2 |
van de Waterbeemd [74] |
| Mozzicconacci | Set of rules to filter for drug-like molecules: Rotatable bonds ≤ 15, rings ≤ 6, oxygen atoms ≥ 1, nitrogen atoms ≥ 1, halogen atoms ≤ 7 |
Mozziconacci [75] |
| Fichert | Rules for permeability based on a small drug set: Molecular Weight ≤ 500, 0 ≤ logD ≤ 3 |
Fichert et al. [76] |
| Muegge method | Bioavailability prediction rules dubbed Muegge method: 200 ≤ MW ≤ 600, −2 ≤ logP ≤ 5, PSA ≤ 150 Å2, number of rings ≤ 7, number of carbons ≥ 4, number of heteroatoms > 1, Number of rotatable bonds ≤ 15, H-bond acceptors ≤ 10, H-bond donors ≤ 5 |
Muegge [77] |
| Egan | Set of rules designed to predict bioavailability: logP ≤ 5.88, PSA ≤ 131.6 Å2 |
Egan et al. [78] |
| Murcko filter | Set of rules derived from the rule of 5 coupled with 1D and 2D descriptor analysis to determine central nervous system activity. MW 200–400, 0 ≤ logP ≤ 5.2, H-bond acceptors ≤ 4, H-bond donor ≤ 3, rotatable bonds ≤ 7 |
Ajay et al. [79] |