Polynitrogen Bicyclic and Tricyclic Compounds as PDE4 Inhibitors

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-<i>d</i>]pyridazine derivatives. Both the new s...

Full description

Saved in:
Bibliographic Details
Main Authors: Claudia Vergelli, Agostino Cilibrizzi, Gabriella Guerrini, Fabrizio Melani, Marta Menicatti, Gianluca Bartolucci, Maria Paola Giovannoni, Letizia Crocetti
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/15/15/8678
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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-<i>d</i>]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 <b>10a</b> and <b>10e,</b> exhibiting IC<sub>50</sub> = 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.
ISSN:2076-3417