CHEMICAL AND DRUG COMPOUND INDEX

The E-state indices may define chemical spaces that are relevant in similarity/ diversity search in chemical databases. This similarity search is based on atom-type E-state indices computed for the query molecule [55]. Each E-state index is converted to a z score, Z =(% -p )/0 , where is the ith E-state atomic index, p is its mean and O is its standard deviation in the entire database. The similarity was computed with the EucHdean distance and with the cosine index and the database used was the Pomona MedChem database, which contains 21000 chemicals. Tests performed for the antiinflamatory drug prednisone and the antimalarial dmg mefloquine as query molecules demonstrated that the chemicals space defined by E-state indices is efficient in identifying similar compounds from drug and drug-tike databases. 

Corwin Hansch, Peter G. Sammes, John B. Taylor, and Colin J. Drayton, Comprehensive Medicinal Chemistry. The Rational Design, Mechanistic Study, and Therapeutic Application of Chemical Compounds, Vol. 6 Cumulative Subject Index and Drug Compendium, Pergamon, Oxford, UK, 1990. 

These sources included, among others, the U. S. Pharmacopoeia and the Merck Index. Thus, the common data base would contain compounds known to be of interest to people in the health field, including drugs, antibiotics, hazardous materials, pesticides, nutrients, and food additives as well as inert compounds in such substances. Chemical Abstracts Service processed these sources against its registry system and added registrations as well as synonyms as they were found in these standard references. The data were delivered to FDA and NLM in a form suitable for processing in their machine systems. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

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