New lead elements for histamine H receptor ligands in the pyrrolo[2,3-d]pyrimidine class.

This work describes the microwave assisted synthesis of twelve novel histamine H receptor ligands. They display pyrrolo[2,3-d]pyrimidine derivatives with rigidized aliphatic amines as warheads. The compounds were screened for HR and HR binding affinities in radioligand displacement assays and the most potent compounds were evaluated for HR binding properties in vitro and in docking studies. The combination of a rigidized HR warhead and the pyrrolo[2,3-d]pyrimidine scaffold resulted in selective activity at the H receptor with a pK value of 6.90 for the most potent compound. A bipiperidine warhead displayed higher affinity than a piperazine or morpholine motif, while a naphthyl moiety in the arbitrary region increased affinity compared to a phenyl derivative. The compounds can be starting points for novel, simply synthesized histamine H receptor ligands.