Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

Hao Yang, Francis N. Murigi, Zhijian Wang, Junfeng Li, Hongjun Jin, Zhude Tu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 ± 0.18, 2.86 ± 0.10, and 3.73 ± 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (>1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain.

Original languageEnglish
Pages (from-to)919-924
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number4
DOIs
StatePublished - Feb 15 2015

Keywords

  • Benzimidazole analogues
  • Cinnoline analogues
  • PET
  • Phosphodiesterase 10A

Fingerprint Dive into the research topics of 'Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors'. Together they form a unique fingerprint.

  • Cite this