High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1(A) receptor. Synthesis and structure - Affinity relationships

Maria Modica, Maria Santagati, Filippo Russo, Carlo Selvaggini, Alfredo Cagnotto, Tiziana Mennini

Research output: Contribution to journalArticlepeer-review


In this work we report the affinity of new thienopyrimidinones for 5- HT1(A)Rs and the selectivity versus α(1A)Rs. The 3-amino-2-[[3-[4-(2- methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin- 4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5- HT(1A)R. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT(1A) Ki 1 499 nM, α1A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H- [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidiN-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and α1ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

Original languageEnglish
Pages (from-to)677-689
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Issue number7-8
Publication statusPublished - Aug 2000


  • 5-HT(A) receptor
  • Ligands
  • Thienopyrimidinones

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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