Lead compound identification databases

The first step in designing a new compound is to find compounds that have even a slight amount of usefulness for the intended purpose. These are called lead compounds. Once such compounds are identified, the problem becomes one of refinement. Computational techniques are a fairly minor part of finding lead compounds. The use of computer-based techniques for lead compound identification is usually limited to searching databases for compounds similar to known lead compounds or known to treat diseases with similar causes or symptoms. 

Which of the following techniques is/are significantly increasing the number of potential lead compounds a combinatorial chemistry b computer databases c high-throughput screening d identification of pharmacophores e all of the above. 

Finn PW, Snarey M. Flexible three-dimensional database searching for the identification of novel lead compounds. In Bioactive Compound Design. Ford. Martyn G. (ed). Oxford. UK Bios Scientific Publishers. 1996 pp. 67-76. 

The discovery of new drugs is a long and complex process. It starts with the identification of a lead compound which elicits a desirable effect. Traditionally, lead compounds have been selected by screening large corporate databases or natural products for biological activity. These compounds are then modified to improve their potency, specificity, and in vivo activity. 

The library search is a mathematical comparison of the unknown compound s spectrum with that of all reference compounds in the database. The aim of the comparison is to find the spectrum that most resembles that of the unknown compound. At the end of the search, the computer software makes a list of all spectra that resemble the unknown spectrum. The software lists the spectra relative to the unknown, along with a reliability or correlation index, irrespective of the library used. Because the object of the library search is to help the analyst and not act as a substitute for him/her, the analyst must manually examine the results. The best approaches to identification are interactive approaches in which the analyst can define filters to reduce the field of investigation. Several different algorithms are used for comparison and can lead to different spectra listings. 

Quantitative studies on structure-acti ily and structure-property relationships are powerful tools m directed drug research In recent years, various strategies have been developed to eharacieri/e and classil y structural patterns by means ol molecular descriptors. It became possible not only to assess diversities or similarities of structure databases, but molecular descriptors also facilitate the identification of potential bioactive molecules from the rapidly increasing number of compound libraries. They even allow for a controlled de-novo design of new lead structures. 

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