- Electronic Effects of Ligand Substitution in a Family of CoII2 PARACEST pH Probes
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We report three new Co2-based paramagnetic chemical exchange saturation transfer (PARACEST) probes with the ability to ratiometrically quantitate pH. A CoII2 complex, [LCo2(etidronate)]-, featuring tetra(carboxamide) and OH-substituted etidronate ligands with opposing pH-dependent CEST peak intensities, was previously shown to exhibit a linear correlation between log(CESTOH/CESTNH) and pH in the pH range 6.5-7.6 that provided a sensitivity of 0.99(7) pH unit-1 at 37 °C. Here, we demonstrate through a series of CF3-functionalized CoII2 complexes [(XL′)Co2(etidronate)]- (X = NO2, F, Me), that modest changes in the electronic structure of CoII centers through remote ligand substitution can significantly affect the NMR and CEST properties of Co2-based PARACEST probes. Variable-pH NMR and CEST analyses reveal that the chemical shifts of the ligand protons are highly affected by the nature of the X substituent. The ratios of OH and NH CEST peak intensities at 115 and 88, 93 and 79, and 88 and 76 ppm for X = NO2, F, and Me, respectively, afford pH calibration curves with remarkably high sensitivities of 1.49(9), 1.48(7), and 2.04(5) pH unit-1 across the series. The 1.5-2-fold enhancement in pH sensitivity for the CF3-functionalized Co2 probes stems from the complete separation of the OH and NH CEST peaks. Furthermore, incorporation of electron-withdrawing CF3 groups shifts the detection window to a more acidic range of pH 6.2-7.4. Finally, the CoII2 complexes are found to be extremely robust toward substitution and oxidation in aqueous solutions. Taken together, these results highlight the unique ability of transition metal-based PARACEST probes to provide a highly sensitive concentration-independent measure of pH and demonstrate that modest ligand modifications can be a powerful tool for optimizing the pH sensing performance of these probes.
- Thorarinsdottir, Agnes E.,Tatro, Scott M.,Harris, T. David
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- PROCESS FOR THE PREPARATION OF 2-AMINO-N-(2,2,2-TRIFLUOROETHYL)-ACETAMIDE AND SALTS THEREOF
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The present invention relates to an improved process for the preparation of 2-amino-N-(2,2,2-trifluoroethyl) acetamide of formula (I) and salts (IA) thereof, in an environment friendly and commercially viable manner in high yield and greater chemical purity.
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Page/Page column 13
(2020/11/12)
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- Discovery and Optimization of Glucose Uptake Inhibitors
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Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.
- Liu, Kevin G.,Kim, Ji-In,Olszewski, Kellen,Barsotti, Anthony M.,Morris, Koi,Lamarque, Christophe,Yu, Xuemei,Gaffney, Jack,Feng, Xiao-Jiang,Patel, Jeegar P.,Poyurovsky, Masha V.
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supporting information
p. 5201 - 5211
(2020/07/10)
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- CXCR2 ANTAGONIST
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A compound as a CXCR2 antagonist and an application thereof in preparing a drug as a CXCR2 antagonist. In particular, the present invention relates to a compound represented by formula (II) or an isomer or pharmaceutically acceptable salt thereof.
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Paragraph 0284-0286
(2020/11/23)
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- A CoII complex for19F MRI-based detection of reactive oxygen species
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A fluorinated, air-stable cobalt(ii) complex serves as a turn-on19F magnetic resonance imaging (MRI) tracer for reactive oxygen species including H2O2. Upon oxidation with H2O2, the complex converts from paramagnetic high spin CoII to diamagnetic low spin CoIII resulting in a chemical shift change and enhancement in19F NMR signal. Further, the oxidation can be reversed in the presence of reductant Na2S2O4. The turn-on response is demonstrated by19F MRI, characterized by a ～2-3 fold enhancement in signal.
- Yu, Meng,Xie, Da,Phan, Khanh P.,Enriquez, José S.,Luci, Jeffrey J.,Que, Emily L.
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supporting information
p. 13885 - 13888
(2016/12/06)
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- TREATMENT OF INFECTIOUS DISEASES WITH GLUCOSE UPTAKE INHIBITORS
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Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.
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Paragraph 0216; 0217
(2017/01/09)
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- GLUCOSE UPTAKE INHIBITORS
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Provided hererin are compounds that modulate glucose uptake activityand are useful for treating cancer, autoimmune diseases, inflammation, infectious diseases, and metabolic diseases. In certain embodiments, the compounds modulate glucose uptake activity by modulating cellular components, including, but not limited to those related to glycolysis and known transporters/co-transporters of glucose such as GLUT1 and other GLUT family members/alternative hexose transporters. In certain embodiments, the compounds have the structure of formula I: Formula (I) wherein the variables have the values disclosed herein.
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Paragraph 0396-0397
(2017/01/09)
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- 2-amino-N-(2, 2, 2-trifluoroethyl) or its salt aminoacetamide compd.
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PROBLEM TO BE SOLVED: To provide a method for producing a substituted 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof. SOLUTION: The method for producing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof comprises, as shown in chemical reaction formula (A), reaction of 2,2,2-trifluoroethylamine or a salt thereof with an acyl compound preferably in the presence of water and an inorganic base, and through this compound, the objective 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof is obtained. COPYRIGHT: (C)2009,JPO&INPIT
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Paragraph 0057
(2017/01/02)
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- METHOD FOR PREPARING 2-AMINO-N-(2,2,2-TRIFLUOROETHYL) ACETAMIDE
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Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an interm
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Page/Page column 22; 31
(2012/04/23)
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- INSECTICIDAL COMPOUNDS BASED ON ARYLTHIOACETAMIDE DERIVATIVES
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The present invention provides compounds of formula (I) wherein R1, R2, R3, R4, G1, n, A1, A2, A3, A4, Y1, Y2, and Y3 are as defined in the claims. The invention also relates to processes and intermediates for preparing these compounds, to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising these compounds and to methods of using these compounds to control insect, acarine, nematode and mollusc pests.
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Page/Page column 215
(2012/12/13)
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