1184-78-7Relevant articles and documents
Genetic variants of flavin-containing monooxygenase 3 (FMO3) in Japanese subjects identified by phenotyping for trimethylaminuria and found in a database of genome resources
Shimizu, Makiko,Koibuchi, Natsumi,Mizugaki, Ami,Hishinuma, Eiji,Saito, Sakae,Hiratsuka, Masahiro,Yamazaki, Hiroshi
, (2021)
The oxygenation of food-derived trimethylamine to its N-oxide is a representative reaction mediated by human flavin-containing monooxygenase 3 (FMO3). Impaired FMO3 enzymatic activity is associated with trimethylaminuria (accumulation of substrate), whereas trimethylamine N-oxide (metabolite) is associated with arteriosclerosis. We previously reported FMO3 single-nucleotide and/or haplotype variants with low FMO3 metabolic capacity using urinary phenotyping and the whole-genome sequencing of Japanese populations. Here, we further analyze Japanese volunteers with self-reported malodor and interrogate an updated Japanese database for novel FMO3 single-nucleotide and/or haplotype variants. After 3 years of follow up, seven probands were found to harbor the known impaired FMO3 variant p.(Gly191Cys) identified in the database or novel variants/haplotypes including p.(Met66Val), p.(Arg223Gln), p.(Glu158Lys;Glu308Gly;Arg492Trp), and p.(Glu158Lys;Glu308Gly;Pro496Ser). The known severe mutation p.(Cys197Ter) (a TG deletion) and four variants including p.(Tyr269His) and p.(Pro496Ser) were first detected in the updated genome panel. Among previously unanalyzed FMO3 variants, the trimethylamine/benzydamine N-oxygenation activities of recombinant p.(Met66Val), p.(Arg223Gln), p.(Tyr269His), p.(Glu158Lys;Glu308Gly;Arg492Trp), and p.(Glu158Lys;Glu308Gly;Pro496Ser) FMO3 variant proteins were severely decreased (Vmax/Km 10% of wild-type). Although the present novel mutations or alleles were relatively rare, both in self-reported Japanese trimethylaminuria sufferers and in the genomic database panel, three common FMO3 missense or deletion variants severely impaired FMO3-mediated N-oxygenation of trimethylamine.
13C GIAO DFT calculation as a tool for configuration prediction of N-O group in saturated heterocyclic N-oxides
Pohl, Radek,Potmischil, Francisc,Dracinsky, Martin,Vanek, Vaclav,Slavetinska, Lenka,Budesinsky, Milos
, p. 415 - 423 (2012)
Tropane, tropinone, pseudopelletierine and cocaine were oxidized in situ in a nuclear magnetic resonance (NMR) tube providing mixtures of exo/endo N-oxides. Observed 13C chemical shifts were correlated with values calculated by gauge-including atomic orbitals density functional theory (DFT) OPBE/6-31G* method using DFT B3LYP/6-31G* optimized geometries. The same method of 13C chemical shift calculation was applied on series of methyl-substituted 1-methylpiperidines and their epimeric N-oxides described in literature. The results show that using this undemanding calculation method enables assignment of configuration of N-O group in N-epimeric saturated heterocyclic N-oxides. The approach enables assigning of the configuration with high degree of certainty even if NMR data of only one isomer are available. An improved method of in situ oxidation of starting amines in an NMR tube is also described. Copyright
The observed and calculated 1H and 13C chemical shifts of tertiary amines and their N-oxides
Pohl, Radek,Dracinsky, Martin,Slavetinska, Lenka,Budesinsky, Milos
, p. 320 - 327 (2011)
A series of model tertiary amines were oxidized in situ in an NMR tube to amine N-oxides and their 1H and 13C NMR spectra were recorded. Next, the chemical shifts induced by oxidation (Δλ) were calculated using different GIAO methods investigating the influence of the method [Hartree-Fock (HF), Moeller-Plesset perturbation, density functional theory (DFT)], the functional applied in the DFT (B3LYP, BPW, OPBE, OPW91) and the basis set used [6-31G*, 6-311G**, 6-311 + + G** and 6-311 + + G(3df,3pd)]. The best results were obtained with the HF/6-311 + + G** and OPBE/6-311 + + G** methods. The computation/experiment comparison approach was used for the configuration prediction of chiral amine N-oxides-(R) and (S)-agroclavine-6-N-oxide.
CRYSTALLINE ANHYDROUS TRIMETHYLAMINE N-OXIDE
Soderquist, John A.,Anderson, Charles L.
, p. 3961 - 3962 (1986)
A rapid, efficient procedure for the preparation of pure, crystalline anhydrous trimethylamine N-oxide from the commercially available dihydrate form of the reagent is described.DMF serves to both allow the distillative removal of water as well as to provide an excellent medium for obtaining large crystals of the pure (mp 225-7oC (dec)), anhydrous material in excellent (94percent) yield.
Infrared matrix isolation studies of the trimethylamine oxide-hydrogen chloride complex
Mielke, Z.
, p. 673 - 676 (1986)
The reaction products of the codeposition of trimethylamine oxide and a HCl/Ar mixture are characterized by diffuse absorption in the region from 1850 to ca 3200 cm-1 and by a strong band at 1700 cm-1.These absorptions are assigned respectively to the O-H+ ...Cl- antisymmetric stretching and in-plane bending modes, which indicates that proton transfer to basic oxygen occurs.
Autoxidation of Trimethylamine in Aqueous Solutions
Chen, Michael J.,Linehan, John C.,Rathke, Jerome W.
, p. 3233 - 3236 (1990)
The autoxidation of trimethylamine in aqueous solutions has been studied at 100 deg C and at O2 pressures up to 153 atm.Trimethylamine N-Oxide is a major product.Its yield accounts for as much as, but never in excess of 50percent, the balance being Me2NH and HCONMe2.The reaction follows second-order kinetics, -d/dt= kPO2, where k= 8.7 x 10-7 atm-1 s-1.In solutions buffered with 0.1 N NaOH, the yield of Me3NO is reduced.These results are interpreted in terms of a rate-limiting electron-transfer reaction between Me3N and dioxygen, followed by reactions dictated by the radical ions, Me3N.+ and O2.- thus generated.It is noted that only one oxygen atom in the O2 molecule is incorporated into Me3NO, the other being used in the sacrificial oxidations to give other products.
SO2F2-mediated oxidation of primary and tertiary amines with 30% aqueous H2O2 solution
Liao, Xudong,Zhou, Yi,Ai, Chengmei,Ye, Cuijiao,Chen, Guanghui,Yan, Zhaohua,Lin, Sen
supporting information, (2021/11/01)
A highly efficient and selective oxidation of primary and tertiary amines employing SO2F2/H2O2/base system was described. Anilines were converted to the corresponding azoxybenzenes, while primary benzylamines were transformed into nitriles and secondary benzylamines were rearranged to amides. For tertiary amine substrates quinolines, isoquinolines and pyridines, their oxidation products were the corresponding N-oxides. The reaction conditions are very mild and just involve SO2F2, amines, 30% aqueous H2O2 solution, and inorganic base at room temperature. One unique advantage is that this oxidation system is just composed of inexpensive inorganic compounds without the use of any metal and organic compounds.
Tetrahydropyrrolization of Resveratrol and Other Stilbenes Improves Inhibitory Effects on DNA Oxidation
Bao, Liang-Liang,Liu, Zai-Qun
, p. 1617 - 1625 (2016/08/28)
The inhibitory effect of resveratrol on DNA oxidation caused by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) was found to be enhanced if the C=C bond in resveratrol was converted into tetrahydropyrrole by reaction with azomethine ylide (CH2=N+(CH3)CH2?). This encouraged us to explore whether the inhibitory activities of other stilbenes could also be increased by the same method. We found that the inhibitory effects of the tetrahydropyrrole derivatives on AAPH-induced oxidation of DNA were higher than those of the corresponding stilbenes, because the tetrahydropyrrole motif can provide hydrogen atoms to be abstracted by radicals. Therefore, the tetrahydropyrrolization offered an advantage for enhancing the antioxidant effects of stilbenes. Notably, (CH3)3SiCH2N(CH3)CH2OCH3(in the presence of CF3COOH) and (CH3)3NO (in the presence of LiN(iPr)2) can be used to generate azomethine ylide for the tetrahydropyrrolization of stilbenes containing electron-withdrawing and -donating groups, respectively.
PYRAZOLE DERIVATIVES AND USES THEREOF AS INHIBITORS OF DLK
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Page/Page column 115, (2015/07/07)
The present invention provides for compounds of formula 0 and various embodiments thereof, and compositions comprising compounds of formula 0 and various embodiments thereof. In compounds of formula 0, the groups R1A, R1B, R1C, R1D, R2, R3, R4, R5 and R6 have the meaning as described herein. The present invention also provides for methods of using compounds of formula 0 and compositions comprising compounds of formula 0 as DLK inhibitors and for treating neurodegeneration diseases and disorders.
SUBSTITUTED PYRAZOLES AND USES THEREOF
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Paragraph 0378, (2015/07/02)
The present invention provides for compounds of formula 0 and various embodiments thereof, and compositions comprising compounds of formula 0 and various embodiments thereof. In compounds of formula 0, the groups R1A, R1B, R1C, R1D, R2, R3, R4, R5 and R6 have the meaning as described herein. The present invention also provides for methods of using compounds of formula 0 and compositions comprising compounds of formula 0 as DLK inhibitors and for treating neurodegeneration diseases and disorders.
