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Updated: Jun 22, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Discovery of a novel class of 2-mercaptohexanoic acid derivatives as highly active PPARalpha agonists
Heiko Zettl1, Ramona Steri, Michael Lämmerhofer
1Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES/LiFF, Max-von-Laue-Str. 9, D-60348 Frankfurt/M., Germany.
Abstract:
A novel and robust scaffold for highly active PPARalpha agonists based on the 2-mercaptohexanoic acid substructure is presented. Systematic structural variation of the substitution pattern of the phenolic backbone yielded detailed SAR especially of ortho and meta substituents. We corroborated the importance of the sulfur atom as well as of the n-butyl chain for PPARalpha activity in the 2-mercaptohexanoic acid head group by preparation of carbon analogs and alpha-unsubstituted derivatives. Compound 10 represents a low nano molar active PPARalpha activator with excellent selectivity towards PPARgamma.
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