Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the α 1-adrenoceptors

Valeria Pittalà, Maria A. Siracusa, Maria N. Modica, Loredana Salerno, Alessandro Pedretti, Giulio Vistoli, Alfredo Cagnotto, Tiziana Mennini, Giuseppe Romeo

Research output: Contribution to journalArticlepeer-review


Three different series of 1H-pyrrolopyrimidine-2,4-dione derivatives were designed and synthesized as ligands for the α 1-adrenergic receptors (α 1-ARs). A microwave-assisted protocol was developed in order to improve purity and yields of some final products. The majority of the synthesized compounds, tested in binding assays, displayed α 1-AR affinities in the nanomolar range. Highest affinity values were found in derivatives 10b and 10c (K i = 1.4 nM for both) whereas compound 10e was endowed with the best profile in term of α 1-AR affinity (K i = 2.71 nM) coupled with high selectivity towards 5-HT 1A receptors (K i >10,000). Molecular docking studies were performed on human α 1-ARs and human 5-HT 1A receptors in order to rationalize the observed experimental affinity and selectivity; these computational studies helped to clarify molecular requirements for the design of high-selective α 1-adrenergic ligands.

Original languageEnglish
Pages (from-to)5260-5276
Number of pages17
JournalBioorganic and Medicinal Chemistry
Issue number17
Publication statusPublished - Sep 1 2011


  • α -Adrenoceptors
  • 1H-Pyrrolopyrimidine-2,4-dione
  • 5-HT Receptors
  • Microwave synthesis
  • Molecular docking
  • QSAR

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry


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