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Modulation of cAMP-specific PDE without emetogenic activity: New sulfide-like PDE7 inhibitors

AuthorsGarcía, Ana M. CSIC; Brea, José; Morales-García, José A. CSIC ORCID; Pérez, Daniel I.; González, A.; Alonso-Gil, Sandra CSIC; Conde, Santiago CSIC ORCID; Cadavid, María Isabel; Loza, María Isabel; Pérez Castillo, Ana CSIC ORCID; Martínez, Ana CSIC ORCID ; Gil, Carmen
Issue Date2014
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 57(20): 8590-8607 (2014)
AbstractA forward chemical genetic approach was followed to discover new targets and lead compounds for Parkinson's disease (PD) treatment. By analysis of the cell protection produced by some small molecules, a diphenyl sulfide compound was revealed to be a new phosphodiesterase 7 (PDE7) inhibitor and identified as a new hit. This result allows us to confirm the utility of PDE7 inhibitors as a potential pharmacological treatment of PD. On the basis of these data, a diverse family of diphenyl sulfides has been developed and pharmacologically evaluated in the present work. Moreover, to gain insight into the safety of PDE7 inhibitors for human chronic treatment, we evaluated the new compounds in a surrogate emesis model, showing nonemetic effects.
Descriptionet al.
Identifiersdoi: 10.1021/jm501090m
issn: 0022-2623
e-issn: 1520-4804
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