Method of generating chemical compounds having desired properties

Abstract

A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.

What is claimed is:  
     
         1 . A computer based method of automatically generating compounds having a prescribed set of properties, comprising the steps of: 
 (1) robotically synthesizing, in accordance with robotic synthesis instructions, a directed diversity chemical library comprising a plurality of chemical compounds;    (2) robotically analyzing said chemical compounds to obtain structure-activity data pertaining thereto;    (3) comparing, under computer control, said structure-activity data of said chemical compounds against said prescribed set of properties to identify any of said chemical compounds substantially conforming to said prescribed set of properties;    (4) classifying, under computer control, said identified chemical compounds as lead compounds;    (5) analyzing, under computer control, said structure-activity data of said compounds and historical structure-activity data pertaining to compounds synthesized and analyzed in the past to derive structure-activity models having enhanced predictive and discriminating capabilities;    (6) identifying, under computer control and in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a set of compounds predicted to exhibit activity/properties more closely matching said prescribed set of properties;    (7) generating, under computer control, robotic synthesis instructions that, when executed, enable robotic synthesis of said set of compounds; and    (8) repeating steps ( 1 )-( 7 ), wherein step ( 1 ) is repeated using said generated robotic synthesis instructions.    
     
     
         2 . The method of  claim 1 , wherein step ( 6 ) comprises the step of: 
 identifying, under computer control and in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a second set of compounds predicted to have a superior ability to validate said structure-activity models, wherein said first and second sets of compounds are not mutually exclusive;    wherein step ( 7 ) comprises the step of generating, under computer control, robotic synthesis instructions that, when executed, enable robotic synthesis of said second set of compounds.    
     
     
         3 . The method of  claim 1 , wherein step ( 6 ) comprises the step of: 
 identifying, under computer control and in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a second set of compounds predicted to have a superior ability to discriminate between said structure-activity; models, wherein said first and second sets of compounds are not mutually exclusive;    wherein step ( 7 ) comprises the step of generating, under computer control, robotic synthesis instructions that, when executed, enable robotic synthesis of said second set of compounds.    
     
     
         4 . The method of  claim 1 , wherein step ( 6 ) comprises the step of: 
 identifying, under computer control and in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a second set of compounds predicted to have a superior ability to validate said structure-activity models, and a third set of compounds predicted to have a superior ability to discriminate between said structure-activity models, wherein said first, second, and third sets of compounds are not mutually exclusive;    wherein step ( 7 ) comprises the step of generating, under computer control, robotic synthesis instructions that, when executed, enable robotic synthesis of said second and third set of compounds.    
     
     
         5 . The method of  claim 1 , wherein step ( 6 ) comprises the step of: 
 identifying, under computer control and in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a second set of compounds predicted to have superior three-dimensional receptor fit, wherein said first and second sets of compounds are not mutually exclusive;    wherein step ( 7 ) comprises the step of generating, under computer control, robotic synthesis instructions that, when executed, enable robotic synthesis of said second set of compounds.