2 research outputs found
Three-Component Assembly of Structurally Diverse 2‑Aminopyrimidine-5-carbonitriles
An
expedient route for the synthesis of libraries of diversely
decorated 2-aminopyrimidine-5-carbonitriles is reported. This approach
is based on a three-component reaction followed by spontaneous aromatization
Effect of Phosphodiesterase 7 (PDE7) Inhibitors in Experimental Autoimmune Encephalomyelitis Mice. Discovery of a New Chemically Diverse Family of Compounds
Phosphodiesterase (PDE) 7 is involved in proinflammatory
processes, being widely expressed both on lymphocytes and on certain
brain regions. Specific inhibitors of PDE7 have been recently reported
as potential new drugs for the treatment of neurological disorders
because of their ability to increase intracellular levels of cAMP
and thus to modulate the inflammatory process, as a neuroprotective
well-established strategy. Multiple sclerosis is an unmet disease
in which pathologies on the immune system, T-cells, and specific neural cells are involved
simultaneously. Therefore, PDE7 inhibitors able to interfere with
all these targets may represent an innovative therapy for this pathology.
Here, we report a new chemically diverse family of heterocyclic PDE7
inhibitors, discovered and optimized by using molecular modeling studies,
able to increase cAMP levels in cells, decrease inflammatory activation
on primary neural cultures, and also attenuate the clinical symptoms
in the experimental autoimmune encephalomyelitis (EAE) mouse model.
These results led us to propose the use of PDE7 inhibitors as innovative
therapeutic agents for the treatment of multiple sclerosis