1397683-80-5Relevant academic research and scientific papers
A Brain-Penetrant and Bioavailable Pyrazolopiperazine BACE1 Inhibitor Elicits Sustained Reduction of Amyloid β in Vivo
Austin, Nigel,De Cleyn, Michel,Gijsen, Harrie J. M.,Macdonald, Gregor J.,Moechars, Diederik,Oehlrich, Daniel,Peschiulli, Aldo,Rombouts, Frederik J. R.,Surkyn, Michel,Trabanco, Andrés A.,Tresadern, Gary,Van Brandt, Sven,Van Gool, Michiel,Vos, Ann
supporting information, p. 76 - 83 (2021/12/14)
We recently disclosed a set of heteroaryl-fused piperazine inhibitors of BACE1 that combined nanomolar potency with good intrinsic permeability and low Pgp-mediated efflux. Herein we describe further work on two prototypes of this family of inhibitors aimed at modulating their basicity and reducing binding to the human ether-a-go-go-related gene (hERG) channel. This effort has led to the identification of compound 36, a highly potent (hAβ42 cell IC50 = 1.3 nM), cardiovascularly safe, and orally bioavailable compound that elicited sustained Aβ42 reduction in mouse and dog animal models.
6,7-DIHYDRO-PYRAZOLO[1,5-A]PYRAZIN-4-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
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Page/Page column 48, (2012/09/21)
The present invention relates to novel 6,7-dihydro-pyrazolo[1,5-a]pyrazin-4-yl-amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACEl, Asp2, or memapsin2. The invention is also directed to pharmaceu
