A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds. ... On the other hand, in the structure of the dual-specific PDE1B, the key histidine residue has been suggested to enable the invariant glutamine to toggle depending on whether it binds cAMP or cGMP.