title: Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as phosphodiesterase type 4 inhibitors.
abstract: 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.
authors.affiliation: Almirall, R&D Centre, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Taltavull
authors.forename: Jordi
authors.initials: J
authors.lastname: Serrat
authors.forename: Jordi
authors.initials: J
authors.lastname: Gràcia
authors.forename: Amadeu
authors.initials: A
authors.lastname: Gavaldà
authors.forename: Míriam
authors.initials: M
authors.lastname: Andrés
authors.forename: Mónica
authors.initials: M
authors.lastname: Córdoba
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Dolors
authors.initials: D
authors.lastname: Vilella
authors.forename: Jorge
authors.initials: J
authors.lastname: Beleta
authors.forename: Hamish
authors.initials: H
authors.lastname: Ryder
authors.forename: Lluís
authors.initials: L
authors.lastname: Pagès
mesh_terms: 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
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011994:Recombinant Proteins; D013876:Thiophenes