Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as phosphodiesterase type 4 inhibitors.

Article Details

Citation

Copy to clipboard

Taltavull J, Serrat J, Gracia J, Gavalda A, Andres M, Cordoba M, Miralpeix M, Vilella D, Beleta J, Ryder H, Pages L

Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as phosphodiesterase type 4 inhibitors.

J Med Chem. 2010 Oct 14;53(19):6912-22. doi: 10.1021/jm100524j.

PubMed ID

20825218 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(R)-Rolipram	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	IC 50 (nM)	498	N/A	N/A	Details
(R)-Rolipram	cAMP-specific 3',5'-cyclic phosphodiesterase 4D	IC 50 (nM)	70	N/A	N/A	Details