Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia

Autor: Yinuo Wu, Qian Zhou, Yan-Fa Yu, Chen Jianwen, Yi-Jing Tian, Zhe Li, Pei Zhang, Yiping Chen, Yu Wang, Yan Chen, Haiju Geng, Chen Zhang, Hai-Bin Luo, Tianhua Zhang
Rok vydání: 2019
Předmět:
Zdroj: Journal of medicinal chemistry. 62(8)
ISSN: 1520-4804
Popis: To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition.
Databáze: OpenAIRE