Undesirable substructures

The first step in prioritization is to ensure that the validated hits do not contain any undesired substructures. This can be achieved using a set of rules such as... 

Fig. 15.8. Substructure mapping, highlighting, and drill-down. Based on on-the-fly substructure query and mapping capability within SciTegic Pipeline Pilot, PGVL Hub allows user to perform substructure queries into a set of target molecules. In the example shown, a set of substructure queries globally collected and validated as undesirable substructure features to be avoided are mapped into target molecules (41b).

The substructure searching tools were applied to eliminate structures containing synthetically or pharmacologically undesirable substructures. After this step, 43 candidates remained. 

The reactions that accomplished the conversion of intermediate 16 into intermediate 23 have taken place very smoothly. It is worth acknowledging that the //-hydroxy lactam moiety did not, at any stage, participate in any undesirable side reaction processes. The stability of the //-hydroxy lactam substructure in the presence of basic reagents is particularly noteworthy since a destructive retro-aldol cleavage reaction could have conceivably occurred on several occasions. The stability of this potentially labile moiety permits all of the desired transformations leading from 16 to 23 to be conducted without prior protection of the C-8 hydroxyl group. 

Calculate the molecular weight and structural alerts (substructures containing undesirable or reactive functionalities) for 5,832 amines (rrrNote 1). 

In addition to physical properties, substructure-based filters can be applied to reduce further the number of molecules, for instance molecules with undesirable functionality for example, reactive or toxic groups can be removed and molecules with particular features (or atoms) can be actively selected. There may be particular functionality that it is desirable to avoid due to assay format, such as fluorophores in fluorescence-based approaches. Structural features for these inclusion and exclusion criteria can be readily formulated using SMILES-based procedures and this type of substructure-based compound selection technique can also be employed in the generation of focused sets of fragment molecules. 

In the production of ferrosilicon the Moeller iron in the charge is added in the form of turnings or shredded iron. For silicon-contents above 45%, a shaft electric furnace is used with a power of 8 to 40 MW, whose substructure is lined with carbon bricks. The undesirable formation of SiC is avoided by rotating or oscillating the furnace. It operates... 

Reject undesirable products by physico-chemical properties and unwanted substructures... 

Many parts of this procedure shown in Figures 13.9 and 13.10 have been automated to allow for a seamless flow of information.The undesirability of certain reagents is defined by the presence of substructures that are known to have toxic side effects and/or be me-tabolically hazardous [122], as well as by the presence of groups that could interfere with or prevent the reaction. Many companies are using lists compiled from analysis of earlier internal screening data. Furthermore, critical information from the chemistry (reaction... 

Constraints In many cases, certain ways ut a reaction which are legal according to f the reaction site, constraints and the eld products which are undesired In the 3) we wish to avoid formation of double bridgeheads (Bredt s rule) We supply, as nstraint, the name of a superatom called s previously defined as substructure 12 toms represent linknodes" and are used to ath of atoms of a given length or range of unstarred atoms in substructure J 2 are ads, the linknodes the three associated double bond in J 2 is to one of the toms, completing an expression of the... 

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