Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Tan, Haizhong; Wu, Wei; Xu, Musheng; Pineda-Lucena, Antonio; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Multitarget Approach for the Treatment of Alzheimer's Disease: Inhibition of Phosphodiesterase 9 (PDE9) and Histone Deacetylases (HDACs) Covering Diverse Selectivity Profiles>, Related Products of 89793-12-4, the main research area is Alzheimer’s disease HDAC inhibition PDE9 inhibition HDAC6 dual inhibitors; Alzheimer’s disease; HDAC6; dual inhibitors; histone deacetylase inhibition; phosphodiesterase 9 inhibition.
Here, we present a series of dual-target phosphodiesterase 9 (PDE9) and histone deacetylase (HDAC) inhibitors devised as pharmacol. tool compounds for assessing the implications of these two targets in Alzheimer’s disease (AD). These novel inhibitors were designed taking into account the key pharmacophoric features of known selective PDE9 inhibitors as well as privileged chem. structures, bearing zinc binding groups (hydroxamic acids and ortho-amino anilides) that hit HDAC targets. These substituents were selected according to rational criteria and previous knowledge from our group to explore diverse HDAC selectivity profiles (pan-HDAC, HDAC6 selective, and class I selective) that were confirmed in biochem. screens. Their functional response in inducing acetylation of histone and tubulin and phosphorylation of cAMP response element binding (CREB) was measured as a requisite for further progression into complete in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo brain penetration profiling. Compound 31b, a selective HDAC6 inhibitor with acceptable brain permeability, was chosen for assessing in vivo efficacy of these first-in-class inhibitors, as well as studying their mode of action (MoA).
ACS Chemical Neuroscience published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia