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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid / antagonists & inhibitors*
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Binding Sites
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Drug Evaluation, Preclinical
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Flufenamic Acid / chemistry*
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Flufenamic Acid / metabolism
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Flufenamic Acid / pharmacology*
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Humans
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Light
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Molecular Structure
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Prealbumin / drug effects*
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Prealbumin / metabolism*
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Protein Conformation
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Protein Folding
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Scattering, Radiation
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Structure-Activity Relationship
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ortho-Aminobenzoates / chemistry*
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ortho-Aminobenzoates / metabolism
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ortho-Aminobenzoates / pharmacology*
Substances
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Amyloid
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Prealbumin
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ortho-Aminobenzoates
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N-(3-carboxyphenyl)anthranilic acid
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Flufenamic Acid