title: Discovery of a novel class of 2-mercaptohexanoic acid derivatives as highly active PPARalpha agonists.
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.
authors: Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES/LiFF, Max-von-Laue-Str. 9, D-60348 Frankfurt/M., Germany.
authors: Heiko
authors: H
authors: Zettl
authors: Ramona
authors: R
authors: Steri
authors: Michael
authors: M
authors: Lämmerhofer
authors: Manfred
authors: M
authors: Schubert-Zsilavecz
mesh_terms: D002208:Caproates / Q000138:chemical synthesis* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D019800:Phenol / Q000737:chemistry; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013455:Sulfur / Q000737:chemistry
chemical_list: D002208:Caproates; D047493:PPAR alpha; D013438:Sulfhydryl Compounds; D019800:Phenol; D013455:Sulfur; D002244:Carbon