- Effect of stilbene and chalcone scaffolds incorporation in clofibric acid on PPARα agonistic activity
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In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, new compounds based on a combination of clofibric acid, the active metabolite of clofibrate, and trans-stilbene, chalcone, and other lipophilic groups were synthesized. They were evaluated for PPARα transactivation activity; all branched derivatives showed an increase of the transcriptional activity of receptor compared to the linear ones. Noteworthy, stilbene and benzophenone branched derivatives activated the PPARα better than clofibric acid.
- Giampietro, Letizia,D'Angelo, Alessandra,Giancristofaro, Antonella,Ammazzalorso, Alessandra,De Filippis, Barbara,Di Matteo, Mauro,Fantacuzzi, Marialuigia,Linciano, Pasquale,Maccallini, Cristina,Amoroso, Rosa
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- Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA1/GPR40), a potential target for the treatment of type II diabetes
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A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA1) has been discovered and explored. The preferred compound 20 (TUG-424, EC50 = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA1 in metabolic diseases such as diabetes or obesity.
- Christiansen, Elisabeth,Urban, Christian,Merten, Nicole,Liebscher, Kathrin,Karlsen, Kasper K.,Hamacher, Alexandra,Spinrath, Andreas,Bond, Andrew D.,Drewke, Christel,Ullrich, Susanne,Kassack, Matthias U.,Kostenis, Evi,Ulven, Trond
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supporting information; experimental part
p. 7061 - 7064
(2009/11/30)
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- Quality control method for manufacturing nucleic acid arrays
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The invention relates to a quality control method for manufacturing biopolymer arrays comprising the use of detectable protecting groups.
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- Probing the scope of the asymmetric dihydroxylation of polymer-bound olefins. Monitoring of HRMAS NMR allows for reaction control and on-bead measurement of enantiomeric excess
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The aim of this study was (I) to define the scope and limitations of the Sharpless asymmetric dihydroxylation (AD) for polymer-bound olefins of different structural types and (II) to elaborate HRMAS NMR methods for the direct on-bead monitoring of the asymmetric dihydroxylation, including the on-bead determination of enantiomeric excess (ee). (I) 2-Methoxy-4-(2- propenyl)phenol (eugenol, E), 10-undecenoic acid (U), and (E)-4- hydroxystilbene (S) were bound to Wang-resin or TentaGel S-OH. These olefins gave low (E, 32%), intermediate (U, 88%), and very high enantiomeric excesses (S, > 99%) when treated with AD mix β in solution. When bound to the polymers, the trend of the enantioselectivities remained the same [S (97%) > U (20-45%) > E (0-3%)]. However, the absolute ee values demonstrate that only the most selective types of substrates in homogeneous solution have practical potential for enantioselective AD on solid phase. (II) HRMAS NMR was successfully used for on-bead monitoring and for the first time for the ee measurement of the polymer-bound dihydroxylation product. As an example, the full assignment of all resonances of polymer-bound 10-undecenoic acid (U) and its dihydroxylation product is presented. For the ee measurement, the polymer-bound dihydroxylation product was derivatized with Mosher's acid. The integration of seven different pairs of resonances in the 13C HRMAS NMR of the diastereomeric Mosher esters gave (in each case) an ee value that agreed within 1% with that determined by chiral HPLC after cleavage of the AD product.
- Riedl, Rainer,Tappe, Robert,Berkessel, Albrecht
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p. 8994 - 9000
(2007/10/03)
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