Discovery of benzodihydroisofurans as novel, potent, bioavailable and brain-penetrant prolylcarboxypeptidase inhibitors

…, ME Lassman, UR Bhatt, MM Garcia-Calvo…

文献索引：Shen, Hong C.; Ding, Fa-Xiang; Jiang, Jinlong; Verras, Andreas; Chabin, Renee M.; Xu, Suoyu; Tong, Xinchun; Chen, Qing; Xie, Dan; Lassman, Mike E.; Bhatt, Urmi R.; Garcia-Calvo, Margarita M.; Geissler, Wayne; Shen, Zhu; Murphy, Beth Ann; Gorski, Judith N.; Wiltsie, Judyann; Roy, Ranabir Sinha; Hale, Jeffrey J.; Pinto, Shirly; Shen, Dong-Ming Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 4 p. 1550 - 1556

全文：HTML全文

被引用次数: 6

摘要

A series of benzodihydroisofurans were discovered as novel, potent, bioavailable and brain- penetrant prolylcarboxypeptidase (PrCP) inhibitors. The structure–activity relationship (SAR) is focused on improving PrCP activity and metabolic stability, and reducing plasma protein binding. In the established diet-induced obese (eDIO) mouse model, compound ent-3a displayed target engagement both in plasma and in brain. However, this compound failed ...