Lead drug discovery programs

One early step in the workflow of the medicinal chemist is to computationally search for similar compounds to known actives that are either available in internal inventory or commercially available somewhere in the world, that is, to perform similarity and substructure searches on the worldwide databases of available compounds. It is in the interest of all drug discovery programs to develop a formal process to search for such compounds and place them into the bioassays for both lead generation and analog-based lead optimization. To this end, various similarity search algorithms (both 2D and 3D) should be implemented and delivered directly to the medicinal chemist. These algorithms often prove complementary to each other in terms of the chemical diversity of the resulted compounds [8]. 

Screening a large pharmaceutical library derived from eukaryotic drug discovery programs afforded pyridopyrimidine 2, a lead targeting the... 

More recently, the focus has moved from diversity in favor of combinatorial libraries designed to target specific receptors or enzymes (12). While these single-target-focused libraries remain a key component of many drug-discovery programs, and are useful in both hit to lead and lead optimization contexts,... 

A smaller (prima ) panel of targets is usually sufficient during the hit to lead phase and lead optimization phases of a drug discovery program to detect promiscuous scaffolds and... 

Not all lead spaces contain areas of activity that qualify as drug spaces. Finding a molecule within one of the drug spaces is the goal of a drug discovery program.13... 

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