Database of drug molecules

Fig. 18.4. Regional permeability from isolated rat gastrointestinal epithelial tissue as a function of log D for a small database of drug molecules. This figure is a replot of data from...

Another way to obtain a library of fragments is to decompose a known database of drug- or lead-like molecules by /j gMifo-retrosynthetic rules like RECAP (Retrosynthetic Combinatorial Analysis Procedure).The RECAP bond cleavage procedure consists of eleven bond cleavage types shown in Figure 7.3. This approach has several advantages ... 

A consensus definition of a drug-like molecule has been derived from the analysis of the CMC database by defining qualifying (covering 80% of drug molecules) ranges of calculated physical properties such as molecular weight, log P, molar refractivity, and number of atoms ... 

Early methods of rational lead optimization sought to find a set of potential leads from a database of small molecules chemically similar to a known lead. The earliest of these techniques was performed by the synthetic chemist in the process of producing the next substance to test and was performed without the aid of a computer. The chemist would make a set of small changes to the structure and determine if those changes had a beneficial or detrimental effect on the efficacy. This process, called analog synthesis, is quite effective. Analog synthesis is the basis for medicinal chemistry and remains an important part of drug discovery today. 

Meanwhile, there are several public drug databases that lend themselves to examination for possible property patterns intrinsic to drags. Several pattern recognition approaches have been tried in which a computer is presented with examples of drugs (molecules from drag databases) and nondrags (typically, ACD database cleaned... 

The main causes of chemical toxicity are side reactions of drug molecules with DNA or proteins, as well as interference with enzymatic systems. There are two databases containing factual toxicological information. One is the RTECS (Registry of Toxic Effects of Chemical Substances), with data on 100 000 compounds. The other is the TOXSYS, with data on 240 000 compounds. ... 

Chen J, Swamidass SJ, Dou Y, Bruand J, Baldi P (2005) ChemBD a public database of small molecules and related chemoinformatics resources. Bioinformatics 21 4133-4139 DrugBank http //www.drugbank.ca. Accessed 1 Feb 2014 WOMBAT http //www.sunsetmolecular.com/. Accessed 1 Feb 2014 MDDR http //accelrys.com/products/databases/bioactivity/mddr.html. Accessed 1 Feb 2014 Scior JT, Bernard P, Medina-Franco JL, Maggiora GM (2007) Large compound databases for structure-activity relationships studies in drug discovery. Mini Rev Med Chem 7 851-860 Leach AR, Gillet VJ (2003) An introduction to chemoinformatics. Kluwer Academic, Dordrecht... 

To evaluate the performance of the descriptors one needs a database of compoimds for which the biological activities are known, e.g.. either the MDDR or the NCI databases. Queries are selected that are typical of a drug-hke molecule and from therapeutic categories that... 

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