2. Academic Validation
  3. Synthesis and biological activity of pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as novel and potent phosphodiesterase type 4 inhibitors

Synthesis and biological activity of pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as novel and potent phosphodiesterase type 4 inhibitors

  • Eur J Med Chem. 2011 Oct;46(10):4946-56. doi: 10.1016/j.ejmech.2011.07.054.
Joan Taltavull 1,  Jordi Serrat,  Jordi Gràcia,  Amadeu Gavaldà,  Mònica Córdoba,  Elena Calama,  José Luis Montero,  Míriam Andrés,  Montserrat Miralpeix,  Dolors Vilella,  Begoña Hernández,  Jorge Beleta,  Hamish Ryder,  Lluís Pagès
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Almirall S.A., R&D Centre, Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Catalonia, Spain.
PMID: 21871695 DOI: 10.1016/j.ejmech.2011.07.054
Abstract

A series of pyrido[3',2':4,5]furo[3,2-d]pyrimidines (PFP) were synthesized and tested for phosphodiesterase type 4 (PDE4) inhibitory activity, with the potential to treat asthma and chronic obstructive pulmonary disease (COPD). Structure-activity relationships within this series, leading to an increase of potency on the enzyme, is presented. Both gem-dimethylcyclohexyl moieties fused to the pyridine ring and the substitution at the 5 position of the PFP scaffold, proved to be key elements in order to get a high affinity in the enzyme.

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