62149-35-3Relevant articles and documents
Comparison of the Maximum Entropy and Additive Potential Methods for Obtaining Rotational Potentials from the NMR Spectra of Samples Dissolved in Liquid Crystalline Solvents. The Case of 4-Nitro-1-(β,β,β-trifluoroethoxy)benzene
Emsley, J. W.,Wallington, I. D.,Catalano, D.,Veracini, C. A.,Celebre, G.,Longeri, M.
, p. 6518 - 6523 (1993)
The maximum entropy (ME) and additive potential (AP) methods of determining the angular distribution functions, p(ω,χ), from the partially-averaged dipolar couplings obtained from the NMR spectra of liquid crystalline samples are compared.Here ω represents the orientation of the mesophase dircetor in a molecular frame, and χ represents bond rotational motion.It is emphasized that these two methods are fundamentally different.Thus, the model-independent ME analysis can determine only pLC(ω,χ) and pLC(χ), which are dependent on the potential of mean torque, Uext(ω,χ), and the subscript LC denotes that these distributions are for the liquid-crystalline phase.The AP method, which is model-dependent, can also determine pLC(ω,χ) and pLC(χ) but in addition yields piso(χ), the distribution of the internal angular coordinate in an isotropic phase, which depends on Uint(χ), an effective, mean conformational energy.The advantages of applying both the ME and AP methods to analyzing the same set of dipolar couplings is illustrated by the case of 4-nitro-1-(β,β,β- trifluoroethoxy)benzene dissolved in two nematic solvents.The ME analysis reveals that motion about the ring-O and O-C(H2) bonds is cooperative, which was then used to guide the choice for the form of Uint(χ) in the treatment of the same data by the AP method.
6-Amino[1,2,5]oxadiazolo[3,4- b]pyrazin-5-ol Derivatives as Efficacious Mitochondrial Uncouplers in STAM Mouse Model of Nonalcoholic Steatohepatitis
Salamoun, Joseph M.,Garcia, Christopher J.,Hargett, Stefan R.,Murray, Jacob H.,Chen, Sing-Young,Beretta, Martina,Alexopoulos, Stephanie J.,Shah, Divya P.,Olzomer, Ellen M.,Tucker, Simon P.,Hoehn, Kyle L.,Santos, Webster L.
supporting information, p. 6203 - 6224 (2020/07/14)
Small molecule mitochondrial uncouplers have recently garnered great interest for their potential in treating nonalcoholic steatohepatitis (NASH). In this study, we report the structure-activity relationship profiling of a 6-amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol core, which utilizes the hydroxy moiety as the proton transporter across the mitochondrial inner membrane. We demonstrate that a wide array of substituents is tolerated with this novel scaffold that increased cellular metabolic rates in vitro using changes in oxygen consumption rate as a readout. In particular, compound SHS4121705 (12i) displayed an EC50 of 4.3 μM in L6 myoblast cells and excellent oral bioavailability and liver exposure in mice. In the STAM mouse model of NASH, administration of 12i at 25 mg kg-1 day-1 lowered liver triglyceride levels and improved liver markers such as alanine aminotransferase, NAFLD activity score, and fibrosis. Importantly, no changes in body temperature or food intake were observed. As potential treatment of NASH, mitochondrial uncouplers show promise for future development.
Palladium-Catalyzed 2,2,2-Trifluoroethoxylation of Aromatic and Heteroaromatic Chlorides Utilizing Borate Salt and the Synthesis of a Trifluoro Analogue of Sildenafil
Peth?, Bálint,Zwillinger, Márton,Csenki, János T.,Káncz, Anna E.,Krámos, Balázs,Müller, Judit,Balogh, Gy?rgy T.,Novák, Zoltán
supporting information, p. 15628 - 15632 (2017/10/20)
A simple and convenient method was developed for the introduction of a 2,2,2-trifluoroethoxy group to various aromatic and heteroaromatic systems. The novel process utilizes aromatic chlorides as substrates, and tetrakis(2,2,2-trifluoroethoxy) borate salt as an inexpensive and readily available fluoroalkoxy source in a palladium-catalyzed cross-coupling reaction. The power of the developed methodology was demonstrated in the synthesis of a fluorous derivative of Sildenafil.
