## 2 In Silico Library Design for Medicinal Chemistry
\begin{table}
\begin{tabular}{l l l} \hline \hline \multicolumn{1}{c}{**Name**} & \multicolumn{1}{c}{**Features/Cutoffs**} & \multicolumn{1}{c}{**Developer/**} \\ \multicolumn{1}{c}{} & \multicolumn{1}{c}{**Reference**} \\ \hline PAINS & Removal of frequent hitters (promiscuous compounds) in HTS assays & Cancer Therapeutics-CRC P/L [64] \\ \hline \multirow{6}{*}{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 \(\leq\) 5, H-bond acceptors \(\leq\) 10, \(-2\leq\) formal \\  & charge \(\leq\) +2, number of rotatable bonds \(\leq\) 8, 200 \(\leq\) \\  & Molecular weight \(\leq\) 500, 20 \(\leq\) number of heavy atoms \(\leq\) 50, \\  & \(-2\leq\) logP \(\leq\) 5 \\ \hline Aggregators & Tanimoto coefficient similarity search to a database of known aggregators & [PERSON] et al. [52] \\ \hline \multirow{2}{*}{Ely Lilly rules} & Hybrid method of physiochemical and functional group filters for identification of promiscuous compounds & [PERSON] at Ely Lilly [67] \\ \hline \multirow{2}{*}{Lipinski (Rule of 5)} & A set of rules for drug-likeness: \\  & Molecular Weight \(\leq\) 500, logP \(\leq\) 5, H-bond donors \(\leq\) 5, \\  & H-bond acceptors \(\leq\) 10 \\ \hline \multirow{2}{*}{Rule of 3} & A set of cutoff rules for lead-like discovery: \\  & Molecular Weight \(\leq\) 300, logP \(\leq\) 3, H-bond donor \(\leq\) 3, \\  & H-bond acceptors \(\leq\) 3 \\ \hline \multirow{4}{*}{Rule of 4} & A set of rules derived from protein–protein interaction \\  & inhibitors: \\  & Molecular Weight \(\geq\) 400, logP \(\geq\) 4, number of rings \(\geq\) 4, \\  & H-bond acceptors \(\geq\) 4 \\ \hline \multirow{4}{*}{Oprea Lead-like and drug-like} & A set of rules based on the lead-like vs. drug-like \\  & comparison: \\  & Molecular Weight \(<\) 450, \(-\)3.5 \(\leq\) logP \(<\) 4.5, \(-\)4 \(\leq\) logD \(\leq\) 4, \\  & number of rings \(\leq\) 4, nonterminal single bonds \(\leq\) 10, \\  & H-bond donor \(\leq\) 5, H-bond acceptor \(\leq\) 8 \\ \hline \multirow{2}{*}{[PERSON]} & A set of rules for drug-likeness with cutoffs: \\  & 180 \(\leq\) Molecular Weight \(\leq\) 480, 40 \(\leq\) molecular refractivity \\  & \(\leq\) 130, \(-\)0.4 \(\leq\) logP \(\leq\) 5.6, 20 \(\leq\) number of atoms \(\leq\) 70 \\ \hline \multirow{2}{*}{[PERSON]} & Two rules to meet the criteria for drug-likeness: \\  & rotatable bonds \(\leq\) 10, Polar Surface Area \(\leq\) 140 Å\({}^{2}\) & [PERSON] et al [72] \\ \hline \multirow{2}{*}{[PERSON]} & Physiological properties of highly-drug like molecules: \\  & Mean Molecular Weight = 356 \\  & Mean logP = 2.1 \\ \hline \multirow{2}{*}{[PERSON]} & Physiological properties for permeability and blood brain \\  & barrier permeability: \\  & Molecular Weight \(\leq\) 450, Polar Surface Area \(\leq\) 90 Å\({}^{2}\) \\ \hline \multirow{2}{*}{[PERSON]} & Set of rules to filter for drug-like molecules: \\  & Rotatable bonds \(\leq\) 15, rings \(\leq\) 6, oxygen atoms \(\geq\) 1, \\  & nitrogen atoms \(\geq\) 1, halogen atoms \(\leq\) 7 \\ \hline \multirow{2}{*}{[PERSON]} & Rules for permeability based on a small drug set: \\  & Molecular Weight \(\leq\) 500, 0 \(\leq\) logD \(\leq\) 3 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Essential filters for efficient library design in medicinal chemistry.