Two groups have recently disclosed solution libraries prepared in mixtures. In each case the groups from Glaxo and Pirrung have synthesised dimeric compounds using amide, ester or carbamate bond-forming reactions. Every library compound was prepared twice in mixtures of different composition. Testing all of these mixtures allows identification of likely active compounds without the need to resynthesise every compound in an active mixture.
In the glaxo example 40 acid chlorides were reacted with 40 amines or alcohols to gives amides or ester respectively in two sets. In the first set, each acid chloride (A) was reacted with a stoichiometric amount of an equimolar mixture of all 40 nucleophiles (N1-40). In the second set each amine or alcohol (N) was reacted with an equimolar mixture of the acid chlorides (A1-40). The 80 mixtures of 40 components each were screened against a wide variety of pharmacological targets, and a positive result from any sample identified half of the structure of a likely active dimeric compound. Weak leads against the neurokinin-3-receptor 1 and matrix metalloproteinase - 1 and 2 were detected.