Leads, lead structures finding

Two copies of the Enzyme-Reaction database are prepared one copy Is accessible through the FORTRAN 77 programs for lead-structure findings discussed in the above section and the other Is on a FACOM relational-database system. 

Distinguishing Molecules of Different Biol< ical Activities and Finding a New Lead Structure - An Example of Ligand-Based Drug Design... 

In recent years, developments in high-throughput screening inspired many pharmaceutical companies to focus and rely on combinatorial chemistry, especially massive parallel synthesis, to find new lead structures. The employed chemistry is often simple and the concept depends on sheer numbers for success. The main research areas were heterocyclic and peptide chemistry, and the resulting structures often lacked complexity and diversity, and most importantly the chance to utilize the evolutionary advantage of natural products with their privileged structures. 

Large arrays of compounds are mostly used at the beginning of medicinal chemistry projects for the fast identification of new lead structures. To increase the odds of finding innovative ligands, such arrays should not contain large numbers of closely related compounds (which are likely to have similar biological properties), but highly diverse compounds with widely different properties. 

Even if the structure of the binding site on the enzyme or the structure of the receptor is known, finding of lead structures remains a difficult challenge. In general, one proceeds as follows ... 

We mention that though the above results are inconvenient for practical use, Theorem 1 can be used to prove stronger results, and Corollary 1 can lead us to find an algorithm for determining whether or not a given benzenoid system has Kekule structures or monotonic path systems. Recently a simple and efficient algorithm of... 

For virtual screening, the situation is somewhat different. Screening can be understood as a search process for finding the best lead structures available in a database. Search problems typically become easier to solve if the search... 

Without the constraints imposed by pre-existing lead structures, identified from the conventional compound sources, like corporate collections or natural extracts, the design of combinatorial libraries for lead finding (discovery libraries) may concentrate on the generation of highly diverse molecules with... 

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