Structure-based design of N-phenyl phenoxazine transthyretin amyloid fibril inhibitors

HM Petrassi, T Klabunde, J Sacchettini…

Index: Petrassi, H. Michael; Klabunde, Thomas; Sacchettini, James; Kelly, Jeffery W. Journal of the American Chemical Society, 2000 , vol. 122, # 10 p. 2178 - 2192

Full Text: HTML

Citation Number: 77

Abstract

Starting with the published 2.0 Å X-ray crystal structure of the transthyretin⊙(flufenamic acid) 2 complex, a simple structure-based ligand design strategy was employed to conceive of N- phenyl phenoxazine transthyretin (TTR) amyloid fibril inhibitors. Fifteen N-phenyl phenoxazines were chemically synthesized and evaluated using a quantitative amyloid fibril assay in vitro. The structure of one of the two most active phenoxazines, 4, bound to TTR ...