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Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as phosphodiesterase type 4 inhibitors. 2010
Joan Taltavull, and
Jordi Serrat, and
Jordi Gràcia, and
Amadeu Gavaldà, and
Míriam Andrés, and
Mónica Córdoba, and
Montserrat Miralpeix, and
Dolors Vilella, and
Jorge Beleta, and
Hamish Ryder, and
Lluís Pagès
Almirall, R&D Centre, Barcelona, Spain.
A series of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines (PTP) has been synthesized and tested as phosphodiesterase IV inhibitors (PDE4), a target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Structure-activity relationships within this series, leading to an increase of potency on the enzyme, are presented. The gem-dimethylcycloalkyl moiety fused to the pyridine ring proved to be a key element of the scaffold in order to get a higher affinity in the enzyme.
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