Drug discovery method

Abstract

A method of obtaining information about a chemically active area of a target molecule, for example for drug discovery, comprising: providing a set of substantially rigid chemical gauges; reacting said target with a plurality of gauges of said set of gauges; assaying a binding of said gauges with said target to obtain a plurality of assay results; and analyzing said assay results to obtain information about said chemically active area.

What is claimed is: 
     
         1 . A method for lead construction, comprising the following steps:
 (a) providing a library of molecules;   (b) generating a pharmacophore map of a target molecule by (i) successfully binding at least 20 low-mass chemical gauges with said target molecule and (ii) analyzing the result of said binding;   (c) computationally screening said library of molecules against said pharmacophore map to identify at least one molecule of said library of molecules that compliments at least 3 points of said pharmacophore map;   (d) computationally modifying said at least one molecule to provide at least one additional attachment point between said molecule and said pharmacophore map by removing moieties and/or adding moieties, to provide said at least one additional attachment point; and   (e) using said at least one molecule to construct said lead.   
     
     
         2 . The method of  claim 1 , further comprising:
 filtering said at least one molecule based on toxicity and ability to synthesize, before said using.   
     
     
         3 . The method of  claim 1 , wherein said moieties comprise Me (methyl) and/or Et (eteyl), and/or Pr (propyl), and/or Ph (phenol), and/or CO2H, and/or OH and/or NH2. 
     
     
         4 . The method of  claim 1 , wherein said library of molecules comprising at least 5% low mass chemical gauges, and wherein said low mass chemical gauges are used for said generating a pharmacophore map. 
     
     
         5 . The method of  claim 1 , wherein said modifying further comprises adding or subtracting H-bond donors/acceptors to a part of said at least one molecule that is not directly involved in binding to said target. 
     
     
         6 . The method of  claim 1 , further comprising linking together at least two molecules of said library of molecules into a single molecule that has a higher affinity to said target than any single molecule of said at least two molecules. 
     
     
         7 . The method of  claim 1 , wherein said computationally screening further comprising testing said at least one molecule for the number of moieties it includes in the required positions and for the availability of attachment points to attach missing moieties. 
     
     
         8 . The method of  claim 1 , wherein said generating further comprising detecting steric clashes by identifying gauges that bind said target molecule with low affinity or that do not bind said target molecule. 
     
     
         9 . The method of  claim 8 , further comprising filtering out at least one molecule from said library of molecules having said steric clashes. 
     
     
         10 . The method of  claim 1 , wherein said computationally modifying further comprises modifying parts of said at least one molecule that are not directly involved in binding to said target, to meet predefined drug-like qualities. 
     
     
         11 . The method of  claim 1 , further comprising determining the therapeutic effect of said at least one molecule based on said at least 3 point and said at least one additional attachment point to said target. 
     
     
         12 . The method of  claim 11 , wherein said therapeutic effect comprises an enhancing effect or an antagonistic effect. 
     
     
         13 . The method of  claim 1 , wherein said map is used to describe one or more profiles of molecules which would be expected to have an effect on the target and wherein said computationally screening further comprising screening said at least one profile of molecules against said library of molecules. 
     
     
         14 . The method of  claim 13 , wherein said one or more profiles are based on geometry of interaction location layout and/or affinity of said interaction locations of said molecules with said target. 
     
     
         15 . The method of  claim 1 , wherein said at least 20 low-mass chemical gauges are selected from a gauges library of at least 10,000 low-mass chemical gauges. 
     
     
         16 . The method of  claim 1 , wherein said at least 20 low-mass chemical gauges bind said target molecule with a binding affinity of at least 1 micro Molar. 
     
     
         17 . The method of  claim 15 , wherein said gauges library comprises at least 10 scaffold molecules. 
     
     
         18 . The method of  claim 17 , wherein each scaffold of said scaffold molecules has at least 3 attachment points for attachment of at least one chemical group to said scaffold. 
     
     
         19 . The method of  claim 18 , wherein said at least one chemical group comprises Me (methyl) and/or Et (eteyl), and/or Pr (propyl), and/or Ph (phenol), and/or CO2H, and/or OH and/or NH2. 
     
     
         20 . The method of  claim 18 , wherein said scaffold comprises at least one ring.