title: Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors.
abstract: Eight small molecules were synthesized to evaluate the structure activity relationships (SAR) of N-substituted anthranilic acids. The molecules were synthesized by benzylation or arylation of methyl anthranilate. A light scattering-based amyloid fibril formation assay was used to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. The m-carboxyphenylated and o-trifluoromethylphenylated anthranilic acids are potent inhibitors that will be subjected to further SAR and structural analysis.
authors.affiliation: Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: V B
authors.initials: VB
authors.lastname: Oza
authors.forename: H M
authors.initials: HM
authors.lastname: Petrassi
authors.forename: H E
authors.initials: HE
authors.lastname: Purkey
authors.forename: J W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D005439:Flufenamic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008027:Light; D015394:Molecular Structure; D011228:Prealbumin / Q000187:drug effects* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*