Synthesis and structure–activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein†,10.1039/D2MD00358A

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Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

Synthesis and structure–activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein†

Maiko Ono,Tomoteru Yamasaki,Katsushi Kumata,Makoto Higuchi,Ming-Rong Zhang,Michael J. Fulham,Andrew Katsifis,Paul A. Keller

RSC Medicinal Chemistry Pub Date : 01/27/2023 00:00:00 , DOI:10.1039/D2MD00358A

Abstract

The pyridinyl-butadienyl-benzothiazole (PBB3 15) scaffold was used to develop tau ligands with improved in vitro and in vivo properties for imaging applications to provide insights into the etiology and characteristics of Alzheimer's disease. The photoisomerisable trans-butadiene bridge of PBB3 was replaced with 1,2,3-triazole, amide, and ester moieties and in vitro fluorescence staining studies revealed that triazole derivatives showed good visualisation of Aβ plaques, but failed to detect the neurofibrillary tangles (NFTs) in human brain sections. However, NFTs could be observed using the amide 110 and ester 129. Furthermore, the ligands showed low to high affinities (K_i = >1.5 mM–0.46 nM) at the shared binding site(s) with PBB3.