Structure-activity profile of substituted purines and inflammation in the delayed hypersensitivity skin reaction

Substituted purines were tested for their effectiveness in inhibiting the delayed hypersensitivity skin reaction (DHSR) caused by tuberculin in the guinea-pig. Among the tested purines were naturally occurring derivatives of guanine and adenine, including cyclic AMP. Based on the structure-activity profile, a class of purines was identified, the members of which were very effective inhibitors of inflammatory aspects of the DHSR and are characterized by a benzyl group in position 9, an amino or alkylamino group in position 6, and various substituents in position 2. This class of 2-substituted-9-benzyladenines was more effective in the DHSR than some antimetabolites, particularly the structurally related mercaptopurines.