B
 Building-blocks, monomers and templates or scaffold
Small molecular weight molecules (MW <250-300) with at least one functional group allowing for reactivity. Can be used for building molecular assemblies using combinatorial techniques or parallel chemistry. These molecules are molecular bricks like a Lego® play.
Building-blocks,
with at least one functional group and one protected functional group.
D
Deconvolution
Methods allowing structure determination from a pool of compounds in a well of micro-plates.
Molecular diversity
Concept widely used in combinatorial and medicinal chemistry to compare molecules. The aim is to higher the information content of a collection of compounds. The diversity of a group of molecules is not a physical constant. It depends on several factors, notably the 2 and 3 dimensional structures and the physico-chemical properties.
Drug discovery
Research that starts from a lead and that, after optimization, results in a new medicine
which will be tested on humans in phase I, II and III clinical trials.
H
High throughput screening (HTS)
Making use of robotics HTS allows for testing of a large number of molecules for a specific activity. The automated process allows for the rapid selection of hits from a vast quantity of compounds. Experiments are usually carried out using 96 well micro titer plates
Hit
Positive answer in a High Throughput Screening test.
Confirmed hit
A hit which biological activity has been confirmed either by deconvolution of the library or synthesis of the molecule in question.
L
Lead compound
A molecule, which was identified as a hit and offers potential for structural variations, as well the identification of a structure-activity relationship. Its chemical structure is used as a starting point for chemical modifications in order to optimize the activity, selectivity or pharmacokinetics. This process can be performed by combinatorial chemistry or by classical chemical synthesis.
Lead discovery
The process of identifying new, active chemical entities. First, a biological target is identified, followed by the development of a high throughput screening test. Finally, the combinatorial libraries are analyzed in order to identify the lead compound.
Chemical library
A chemical library or compound library is a collection of stored chemicals usually used ultimately in high-throughput screening or industrial manufacture. The chemical library can consist in simple terms of a series of stored chemicals. Each chemical has associated information stored in some kind of database with information such as the chemical structure, purity, quantity, and physiochemical characteristics of the compound.
In drug discovery high-throughput screening, it is desirable to screen a drug target against a selection of chemicals that try to take advantage of as much of the appropriate chemical space as possible.
Primary Librairies (hit generation)
Primary chemical libraries are usually designed by chemists and chemoinformatics scientists and synthesized by organic chemistry and medicinal chemistry. The method of chemical library generation usually depends on the project. Typically, a range of chemicals is screened against a particular drug target or disease model, and the preliminary "hits", or chemicals that show the desired activity, are re-screened to verify their activity. Once they are qualified as a "hit" by their repeatability and activity, these particular chemicals are registered and analysed. In drug discovery high-throughput screening, it is desirable to screen a drug target against a selection of chemicals that try to take advantage of as much of the appropriate chemical space as possible. The chemical space of all possible chemical structures is extraordinarily large. However, since many molecular interactions cannot be predicted, the wider the chemical space that is sampled by the primary chemical library, the better the chance that high-throughput screening will find an "hit" -- a chemical with an appropriate interaction in a biological model that might be developed into a drug. In order to increase the rate of “hit finding”, you can restrict the chemical space by introducing specific fragments representative of the targets.
Focused libraries (lead generation)
The method of chemical library generation usually depends on the project. Typically, a range of chemicals is screened against a particular drug target or disease model. Commonalities among the different chemical groups are studied as they are often reflective of a particular chemical subspace. Additional chemistry work may be needed to further optimize the chemical library in the active portion of the subspace. When it is needed, more synthesis is completed to extend out the chemical library in that particular subspace by generating more compounds that are very similar to the original hits. This new selection of compounds within this narrow range are further screened and then taken on to more sophisticated models for further validation in the Drug Discovery Hit to Lead process.
M
Monomers
Building blocks with only one reactive function.
T
Templates,
scaffold
Molecules in general cyclic with, at least two chemical reactive functions orthogonally protected allowing molecular assembling in order to probe the chemical space.
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