Rational design and synthesis of new PARP1 inhibitors

A preliminary simulation of bioactive compounds followed by their synthesis have been carried out: a set of new fragment PARP1 inhibitors – 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one derivatives – have been obtained. Molecular simulation has shown that binding is characterized by correlated hydrogen bonds with PARP1 and displacement of the highly-conservative water molecule by a polar group.