Modulation of cAMP-Specific PDE without Emetogenic Activity: New Sulfide-Like PDE7 Inhibitors

García, Ana M. ; Brea, José ; Morales-García, Jose A. ; Perez, Daniel I. ; González, Alejandro ; Alonso-Gil, Sandra ; Gracia-Rubio, Irene ; Ros-Simó, Clara ; Conde, Santiago ; Cadavid, María Isabel ; Loza, María Isabel ; Perez-Castillo, Ana ; Valverde, Olga ; Martinez, Ana ; Gil, Carmen

Resumen: A 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.

Idioma: Inglés

DOI: 10.1021/jm501090m

Año: 2014

Publicado en: Journal of medicinal chemistry 57, 20 (2014), 8590-8607
ISSN: 0022-2623

Factor impacto JCR: 5.447 (2014)

Categ. JCR: CHEMISTRY, MEDICINAL rank: 3 / 59 = 0.051 (2014) - Q1 - T1

Tipo y forma: Artículo (Versión definitiva)