Drug-likeness library design

Wang, J., Ramnarayan, K. Towards designing drug-like libraries a novel computational approach for prediction of drug feasibility of compounds. J. Comb. Chem. 1999, 7(6), 524—533. 

These common drug scaffolds often serve as the basis for DOS of drug-like libraries [29]. Furthermore, since synthetic drugs are most useful when orally bioavailable, these library designs often take into account physicochemical properties that have been found to correlate with this feature [30], Notably, many of the current commercially available libraries still fail to recapitulate these properties [28]. Thus, efforts continue to develop drug-like libraries that match the properties of known synthetic drugs more closely. 

III Designing drug-like libraries A Full combinatorial arrays or cherry- 154... 

Principal Component Analysis as a Tool for Library Design A Case Study Investigating Natural Products, Brand-Name Drugs, Natural Product-Like Libraries, and Drug-Like Libraries... 

Computational approaches towards the rational design of drug-like compound libraries. Comb. Chem. High-Throughput Screen. 2001, 4, 453 75. 

Mitchell, T., Showell, G. A. Design strategies for building drug-like chemical libraries. Curr. Opin. Drug Discov. Dev. 2001, 4, 314-318. 

Matter, H., Baringhaus, K. H., Naumann, T., Kiabunde, T., Pirard, B., Computational approaches towards the rational design of drug-like compound libraries, Comb. Chem. High Throughput Screen. 2001, 4, 453-475. 

The genesis of in silico oral bioavailability predictions can be traced back to Lip-inski s Rule of Five and others qualitative attempts to describe drug-like molecules [13-15]. These processes are useful primarily as a qualitative tool in the early stage library design and in the candidate selection. Despite its large number of falsepositive results, Lipinski s Rule of Five has come into wide use as a qualitative tool to help the chemist design bioavailable compounds. It was concluded that compounds are most likely to have poor absorption when the molecular weight is >500, the calculated octan-l-ol/water partition coefficient (c log P) is >5, the number of H-bond donors is >5, and the number of H-bond acceptors is >10. Computation of these properties is now available as an ADME (absorption, distribution, metabolism, excretion) screen in commercial software such as Tsar (from Accelrys). The rule-of-5 should be seen as a qualitative, rather than quantitative, predictor of absorption and permeability [16, 17]. 

Fig. 18.2 Elaboration-based strategies. Left In SHAPES screening [3], simple drug-like scaffolds are screened using ligand-detected experiments. In the follow-up step, information about binding scaffolds is used to design a follow-up library comprised of analogous compounds. Successive rounds of screening lead to increasingly complex...

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