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17.17 Combinatorial Chemistry
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[ Markush | Create Markush | Enumerate by Scaffold | Enumerate Markush | R-Group Decomposition | Decompose Markush | Enumerate by Reaction | Reaction ]

17.17.1 Create/Modify Markush


To create or modify a Markush Structure:

Step 4: Create Markush Combinatorial Library

17.17.2 How to create a Markush structure.


17.17.3 Enumerate by Scaffold


To enumerate a library based on R-groups you first need to draw a sketch of the structure and display it in a chemical spreadsheet. To do this:

The next step is to read into ICM or construct a table of substituents. You can read in an SDF, mol, smiles file or extract fragments. If you do not want the first atom of the substituents to be the attachment point you need to define the attachment point. Attachment points are automatically assigned when you extract fragments or you can define them manually by:

Next enumerate the library

A new table will be produced called T_enum with the Template structure highlighted in red.

17.17.4 How to enumerate a Markush library.


17.17.5 R-Group Decomposition


To decompose a library into fragments based on a Markush scaffold (opposite of R-group (Markush) enumeration):

17.17.6 How to decompose a library based on a Markush structure.


17.17.7 Enumerate by Reaction


Reactions can be drawn using the ICM Molecular Editor. Reactants should be drawn side-by-side (no + sign is necesary) and separated from the product using the arrow. See example shown below:

This example is available in the ICM distribution as example_reaction1.icb. The reaction is the Hantzsch Dihydropyridine (Pyridine) Synthesis. This reaction allows the preparation of dihydropyridine derivatives by condensation of an aldehyde with two equivalents of a �-ketoester in the presence of ammonia. Subsequent oxidation (or dehydrogenation) gives pyridine-3,5-dicarboxylates, which may also be decarboxylated to yield the corresponding pyridines.

In this example we have two reactants therefore it is necesary to have two reactant substructure tables loaded into ICM. ICM will match the substructure drawn in the reaction with the chemicals in thereactant table.

reactant 1 table:

To apply a reaction:

A table of Products will be then displayed in a table called T_out. Columns in T_out labeled "rct" display which reactants were used to build the product.

17.17.8 How to enumerate a chemical library by reaction.



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