Fragments Screen Files

Selection of the reagents was based on the Pfizer internal compound collection which allowed speedy acquisition of any selected compound. A set of primary amines, secondary amines, and carboxylic acids which were not commercially available were chosen for consideration. These acids and amines were designed by medicinal chemists via a Pfizer internal screening file enrichment effort to be novel and diverse, and more importantly, were not part of any existing Pfizer fragment collection. The MW... 

An extension of SOCRATES to handle chemical reactions, called CONTRAST, has also been developed at Sandwich, again with some collaboration from Peter Willett at Sheffield. In SOCRATES the precursors of our company compounds are stored in the compound registry file, and so application of a reaction site detection algorithm to the starting material and product generates a set of modified connection tables and fragment screens, and a set ofreaction bit-screens. The substructure search graphical structure input menu was modified to enable the chemist to identify the atoms involved in the reaction, but otherwise is essentially the same interface as in SOCRATES. 

The system identifies the structures in the file which have more than a threshold number of structural fragments (screens) in common with the target, and from these chooses a cut-off number of screens in common so as to give a browsing set of appropriate size, typically about 50 structures. A measure of similarity between each of these structures and the target is calculated, and they are ranked in order of similarity to the target for display to the user. 

These data-sets were extracted from the CD-ROM version of RTECS by specifjdng the retrieval of those records that had one of the particular t3q>es of data listed above. Records having WLNs were then extracted from these downloaded files the WLNs were converted to connection tables and these tables were then used to generate fragment screen records for each of the structures. Specifically,... 

As a result, screening systems based on automatically-generated structural fragments have been developed. These fragments consist of small groups of connected atoms and bonds, and if the file structure does not contain all the fragments found in the query, there is no point in looking at it further. 

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