Design, Synthesis, and Biological Evaluation of a Novel Class of γ-Secretase Modulators with PPARγ Activity was written by Hieke, Martina;Ness, Julia;Steri, Ramona;Dittrich, Michaela;Greiner, Christine;Werz, Oliver;Baumann, Karlheinz;Schubert-Zsilavecz, Manfred;Weggen, Sascha;Zettl, Heiko. And the article was included in Journal of Medicinal Chemistry in 2010.Reference of 2968-93-6 This article mentions the following:
We present a novel class of dual modulators of γ-secretase and peroxisome proliferator-activated receptor γ (PPARγ) based on the structure of 2-(bis(phenethoxy)pyrimidin-2-ylthio)hexanoic acid (I, IC50(Aβ42) = 22.8 μM, EC50(PPARγ) = 8.3 μM). The modulation of both targets with approved drugs (i.e., amyloid-β 42 (Aβ42)-lowering NSAIDs for γ-secretase and glitazones for PPARγ) has demonstrated beneficial effects in in vitro and in vivo models of Alzheimer’s disease (AD). However, although NSAIDs and PPARγ agonists share similar structural features, no druglike compounds with dual activities as γ-secretase modulators (GSMs) and PPARγ agonists have been designed so far. On the basis of our initial lead structure I, we present the structure-activity relationships (SARs) of broad structural variations. A significant improvement was reached by the introduction of p-trifluoromethyl substituents at the Ph residues yielding compound 2-(4,6-bis(4-(trifluoromethyl)phenethoxy)pyrimidin-2-ylthio)hexanoic acid (II, IC50(Aβ42) = 6.0 μM, EC50(PPARγ) = 11.0 μM) and the replacement of the two Ph residues of I by cyclohexyl yielding a compound with IC50(Aβ42) = 5.1 μM and EC50(PPARγ) = 6.6 μM. In the experiment, the researchers used many compounds, for example, 2-(4-(Trifluoromethyl)phenyl)ethanol (cas: 2968-93-6Reference of 2968-93-6).
2-(4-(Trifluoromethyl)phenyl)ethanol (cas: 2968-93-6) belongs to alcohols. Under appropriate conditions, inorganic acids also react with alcohols to form esters. To form these esters, a wide variety of specialized reagents and conditions can be used. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Reference of 2968-93-6
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