Ring-opened aminothienopyridazines as novel tau aggregation inhibitors

M Moir; S W Chua; T Reekie; A D Martin; A Ittner; L M Ittner; M Kassiou

doi:10.1039/c6md00306k

Ring-opened aminothienopyridazines as novel tau aggregation inhibitors

Medchemcomm. 2017 May 5;8(6):1275-1282. doi: 10.1039/c6md00306k. eCollection 2017 Jun 1.

Authors

M Moir¹, S W Chua², T Reekie¹, A D Martin^{2

3}, A Ittner², L M Ittner^{2

4}, M Kassiou¹

Affiliations

¹ School of Chemistry , University of Sydney , Sydney , NSW 2006 , Australia . Email: michael.kassiou@sydney.edu.au.
² Dementia Research Unit , School of Medical Sciences , Faculty of Medicine , University of New South Wales , Sydney , NSW 2052 , Australia.
³ School of Chemistry , University of New South Wales , Sydney , NSW 2052 , Australia.
⁴ Neuroscience Research Australia , Sydney , NSW 2031 , Australia.

Abstract

Aminothienopyridazines (ATPZs) have demonstrated efficacy, in vitro, as tau protein aggregation inhibitors. Modifications were made to the ATPZ scaffold to determine the importance of certain structural features for activity. More specifically, ring-opened analogues detached at the nitrogen-nitrogen bond of the pyridazine, were synthesized and their inhibitory activity evaluated. Preliminary data suggests that the ring-opened structures retain inhibitory activity, independent of tau oxidation. The structures detailed represent the beginnings of a deconstruction-reconstruction-elaboration study, with the aim of identifying simpler scaffolds, which retain activity and can be optimized in terms of physiochemical properties.