Polynitrogen Bicyclic and Tricyclic Compounds as PDE4 Inhibitors
Source abstract
Abstract
We report here two new series of designed PDE4 inhibitors, the first one showing the quinoline scaffold recently investigated by us through a fragment-based drug design strategy, and the second consisting of pyrazolo [1′,5′:1,6]pyrimido[4,5-d]pyridazine derivatives. Both the new series were subjected to biological studies to assess their inhibitory effect on PDE4 enzymes, supported by molecular modelling experiments, to rationalize the different activities recorded in the in vitro tests. Interesting results were achieved for two compounds belonging to the tricyclic series, namely 10a and 10e, exhibiting IC50 = 62 and 175.5 nM, respectively. These results could represent the starting point for further studies with the aim of developing new and effective PDE4 inhibitors for biomedical investigations.
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Research context
OpenAlex topics: Phosphodiesterase function and regulation · Phenothiazines and Benzothiazines Synthesis and Activities · Cholinesterase and Neurodegenerative Diseases
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of NEUROFARBA-Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy
Institute of Pharmaceutical Science, King’s College London, Stamford Street, London SE1 9NH, UK
Medicines Development, Centre for Therapeutic Innovation, University of Bath, Bath BA2 7AY, UK
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