Document Report Card

ID: ALA3425427

Journal: ACS Med Chem Lett

Title: Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors.

Authors: Rombouts FJ, Tresadern G, Buijnsters P, Langlois X, Tovar F, Steinbrecher TB, Vanhoof G, Somers M, Andrés JI, Trabanco AA.

Abstract: A novel series of pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor occupancy data are given for two representative compounds 6 and 12.

CiteXplore: 25815146

DOI: 10.1021/ml500463t