125130-98-5Relevant articles and documents
1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor γ and promote the browning of white adipose
Xu, Shilin,Mao, Liufeng,Ding, Ping,Zhuang, Xiaoxi,Zhou, Yang,Yu, Lei,Liu, Yingxue,Nie, Tao,Xu, Tingting,Xu, Yong,Liu, Jinsong,Smaill, Jeff,Ren, Xiaomei,Wu, Donghai,Ding, Ke
, p. 3751 - 3760 (2015/07/27)
The estrogen-related receptor γ (ERRγ) is a potential molecular target for the development of small molecules to stimulate the adipose browning process, which may represent a novel attractive strategy to treat obesity related disorders. The receptor possesses a very small ligand binding cavity and therefore identification of small molecule ERRγ modulators is a considerable challenge. We have successfully designed and synthesized a series of 1-benzyl-4-phenyl-1H-1,2,3-triazoles and demonstrated that they improve the transcriptional functions of ERRγ, potently elevating both the mRNA levels and the protein levels of ERRγ downstream targets. One of the most promising compounds, 4-(1-(4-iso-propylbenzyl)-1H-1,2,3-triazol-4-yl)benzene-1,2-diol (2e) was further shown to directly bind with the ERRγ ligand binding domain (ERRγ-LBD) in an isothermal calorimetric (ITC) assay and to thermally stabilize ERRγ-LBD protein by increasing its melting temperature (Tm) as demonstrated by circular dichroism (CD) spectroscopy. Furthermore, 2e potently stimulates the adipocyte browning process and induces mitochondrial biogenesis both in vitro and in vivo, suggesting the considerable therapeutic potential of this compound for the treatment of obesity and related disorders.
Palladium-catalyzed cyclization of o-alkynylphenols with allyl carbonates. A regioselective synthesis of 2-substituted-3-allylbenzo[b]furans
Cacchi, Sandro,Fabrizi, Giancarlo,Moro, Leonardo
, p. 741 - 745 (2007/10/03)
2-Substituted-3-allylbenzo[b]furans 3 can be prepared from o-alkynylphenols 1 and allyl carbonates 2 through a palladium-catalyzed O-allylation/cyclization sequence. Two basic procedures have been developed: a stepwise method based on the isolation of O-allyl derivatives 4 and their subsequent cyclization to 3 (procedure A) and a one-pot reaction omitting the isolation of 4 (procedure B). The cyclization of 4 in the presence of the electron-rich sterically-encumbered ligand tris(2,4,6-trimethoxyphenyl)phosphine (ttmpp) exhibits remarkable regioselectivity in that 3-allylbenzofurans in which the benzofuryl unit is bound to the less substituted allyl terminus are formed almost exclusively. Some loss of the stereochemistry of the carbon-carbon double bond is observed.
53. Acid-Catalyzed Cyclization Rections of Substituted Acetylenic Ketones: A New Approach for the Synthesis of 3-Halofurans, Flavones, and Styrylchromones
Obrecht, Daniel
, p. 447 - 456 (2007/10/02)
Acetylenic acetals of type I (Scheme 1) and acetylenic ketones of type III (Scheme 1), 37 and 38 (Scheme 7) are versatile synthetic precursors for the synthesis of various heterocycles by acid-catalyzed cyclization reactions.By this way, substituted 3-halofurans of type II and IV (Scheme 1) and flavones and styrylchromones (Scheme 7) can be synthesized in good-to-excellent yields.The high degree of regioselectivity in the synthesis of the 3-halofurans (Scheme 4) is the result of the regioselective β-addition of HX (X = Cl, Br, I) to the acetylenic aldehyde and acetylenic ketone moieties.A possible mechanism is depicted in Scheme 5.Since 3-halofurans can easily be metalated and substituted, this approach constitutes a new synthesis of highly substituted furans.
