25851-08-5Relevant academic research and scientific papers
Discovery of a Potent Thiazolidine Free Fatty Acid Receptor 2 Agonist with Favorable Pharmacokinetic Properties
Hansen, Anders H?jgaard,Sergeev, Eugenia,Bolognini, Daniele,Sprenger, Richard R.,Ekberg, Jeppe Hvidtfeldt,Ejsing, Christer S.,McKenzie, Christine J.,Rexen Ulven, Elisabeth,Milligan, Graeme,Ulven, Trond
supporting information, p. 9534 - 9550 (2018/10/24)
Free fatty acid receptor 2 (FFA2/GPR43) is a receptor for short-chain fatty acids reported to be involved in regulation of metabolism, appetite, fat accumulation, and inflammatory responses and is a potential target for treatment of various inflammatory and metabolic diseases. By bioisosteric replacement of the central pyrrolidine core of a previously disclosed FFA2 agonist with a synthetically more tractable thiazolidine, we were able to rapidly synthesize and screen analogues modified at both the 2- and 3-positions on the thiazolidine core. Herein, we report SAR exploration of thiazolidine FFA2 agonists and the identification of 31 (TUG-1375), a compound with significantly increased potency (7-fold in a cAMP assay) and reduced lipophilicity (50-fold reduced clogP) relative to the pyrrolidine lead structure. The compound has high solubility, high chemical, microsomal, and hepatocyte stability, and favorable pharmacokinetic properties and was confirmed to induce human neutrophil mobilization and to inhibit lipolysis in murine adipocytes.
Rh(III)-Catalyzed Redox-Neutral Annulation of Primary Benzamides with Diazo Compounds: Approach to Isoquinolinones
Wu, Youzhi,Sun, Peng,Zhang, Kaifan,Yang, Tie,Yao, Hequan,Lin, Aijun
, p. 2166 - 2173 (2016/03/15)
Reported herein is a Rh-catalyzed redox-neutral annulation of primary benzamides with diazo compounds, representing an efficient and economic protocol to isoquinolinones. The procedure exhibited good functional group tolerability, scalability, and regioselectivity, obviating the need for oxidants, and only environmentally benign N2 and H2O were released. Further utilization of the method provided an alternative route to functionalized isoquinolines.
Rhodium-catalyzed C-H alkynylation of arenes at room temperature
Feng, Chao,Loh, Teck-Peng
supporting information, p. 2722 - 2726 (2014/03/21)
The rhodium(III)-catalyzed ortho C-H alkynylation of non-electronically activated arenes is disclosed. This process features a straightforward and highly effective protocol for the synthesis of functionalized alkynes and represents the first example of merging a hypervalent iodine reagent with rhodium(III) catalysis. Notably, this reaction proceeds at room temperature, tolerates a variety of functional groups, and more importantly, exhibits high selectivity for monoalkynylation. Hot rhod: A rhodium-catalyzed, electronically reversed Sonogashira reaction between unbiased arenes and the hypervalent iodine reagent 1 proceeds through C-H activation. This reaction displays excellent functional-group tolerance and high efficiency, and thus opens a new synthetic pathway to access functionalized alkynes. Cp=C5Me5, DCE=1,2-dichloroethane, Piv=pivaloyl, TIPS=triisopropylsilyl.
Piperazine-2,3-dicarboxylic acid derivatives as dual antagonists of NMDA and GluK1-containing kainate receptors
Irvine, Mark W.,Costa, Blaise M.,Dlaboga, Daniel,Culley, Georgia R.,Hulse, Richard,Scholefield, Caroline L.,Atlason, Palmi,Fang, Guangyu,Eaves, Richard,Morley, Richard,Mayo-Martin, Maria B.,Amici, Mascia,Bortolotto, Zuner A.,Donaldson, Lucy,Collingridge, Graham L.,Molnár, Elek,Monaghan, Daniel T.,Jane, David E.
supporting information; experimental part, p. 327 - 341 (2012/03/11)
Competitive N-methyl-d-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative
