558-43-0Relevant articles and documents
Biotransformation of 12C- and 2-13C-labeled methyl tert-butyl ether, ethyl tert-butyl ether, and tert-butyl alcohol in rats: Identification of metabolites in urine by 13C nuclear magnetic resonance and gas chromatography/mass spectrometry
Bernauer, Ulrike,Amberg, Alexander,Scheutzow, Dieter,Dekant, Wolfgang
, p. 651 - 658 (1998)
The biotransformation of the fuel oxygenates methyl tert-butyl ether (MTBE) and ethyl tertbutyl ether (ETBE) was studied in rats after inhalation exposure; the biotransformation of the initial metabolite of these ethers, tert-butyl alcohol, was studied after oral gavage. To study ether metabolism, rats were exposed for 6 h to initial concentrations of 2000 ppm of MTBE or ETBE, respectively [2-13C]MTBE and [2-13C]ETBE. Urine was collected for 48 h after the end of the exposure, and urinary metabolites were identified by 13C NMR (13C-labeled ethers) and gas chromatography/mass spectrometry (GC/MS) (12C- and 13C-labeled ethers). To study tert-butyl alcohol metabolism, rats were dosed either with tert-butyl alcohol at natural carbon isotope ratio or with 13C-enriched tert-butyl alcohol (250 mg/kg of body weight), urine was collected, and metabolites were identified by NMR and GC/MS. tert-Butyl alcohol was identified as a minor product of the biotransformation of MTBE and ETBE. In addition, small amounts of a tert- butyl alcohol conjugate, likely a glucuronide, were present in the urine of the treated animals. Moreover, the mass spectra obtained indicate the presence of small amounts of [13C]acetone in the urine of [13C]MTBE and [13C]ETBE-treated rats. 2-Methyl-1,2-propanediol, 2-hydroxyisobutyrate, and another unidentified conjugate of tert-butyl alcohol, most probably a surf ate, were major urinary metabolites of MTBE and ETBE as judged by the intensities of the NMR signals. In [13C]-tert-butyl alcohol-dosed rats, [13C]acetone, tert-butyl alcohol, and its glucuronide represented minor metabolites; as with the ethers, 2-methyl-1,2-propanediol, 2- hydroxyisobutyrate, and the presumed tert-butyl alcohol sulfate were the major metabolites present. In one human individual given 5 mg/kg [13C]- tert-butyl alcohol orally, 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate were major metabolites in urine detected by 13C NMR analysis. Unconjugated tert-butyl alcohol and tert-butyl alcohol glucuronide were present as minor metabolites, and traces of the presumed tert-butyl alcohol sulfate were also present. Our results suggest that tert-butyl alcohol formed from MTBE and ETBE is intensively metabolized by further oxidation reactions. Studies to elucidate mechanisms of toxicity for these ethers to the kidney need to consider potential toxicities induced by these metabolites.
The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist
Moir, Michael,Lane, Samuel,Montgomery, Andrew P.,Hibbs, David,Connor, Mark,Kassiou, Michael
, (2020/12/21)
The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
KIF18A INHIBITORS
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Paragraph 0283, (2020/07/14)
Compounds of formula (I): (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.
Synthesis, Characterization and Catalytic Application of Pyridine-Bridged N-Heterocyclic Carbene–Ruthenium Complexes in the Hydrogenation of Carbonates
Chen, Jiangbo,Zhu, Haibo,Chen, Jinjin,Le, Zhang-Gao,Tu, Tao
supporting information, p. 2809 - 2812 (2017/10/23)
A series of bulky pyridine-bridged NHC–Ru complexes have been rationally designed and synthesized; these exhibited very high catalytic activity in the hydrogenation of cyclic and linear carbonates under mild reaction conditions. In the presence of catalytic amounts of a weak base, a broad range of substrates with different ring size and steric bulk were well tolerated, providing methanol and the corresponding diols in excellent yields with a catalyst loading as low as 0.5 mol %.