Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as phosphodiesterase type 4 inhibitors.
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.
Taltavull
Joan
J
Almirall, R&D Centre, Barcelona, Spain.
Serrat
Jordi
J
Gràcia
Jordi
J
Gavaldà
Amadeu
A
Andrés
Míriam
M
Córdoba
Mónica
M
Miralpeix
Montserrat
M
Vilella
Dolors
D
Beleta
Jorge
J
Ryder
Hamish
H
Pagès
Lluís
L
D006801:Humans; D058988:Phosphodiesterase 4 Inhibitors; D010843:Pichia; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry
D058988:Phosphodiesterase 4 Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011994:Recombinant Proteins; D013876:Thiophenes