14325-35-0Relevant articles and documents
Development of a practical and scalable synthesis of anti-HBV drug Y101
Hu, Zhan-Xing,Zhang, Yan-Gong,An, Qiao,Xu, Bi-Xue,Pan, Wei-Dong,Cao, Pei-Xue,Liu, Chang-Xiao,Huang, Zheng-Ming,Xia, Wen,Qiu, Jing-Ying,Liang, Guang-Yi
, p. 9592 - 9600 (2014)
The process research and development of a practical and scalable synthetic method towards Anti-HBV Drug N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) was described. Initial synthetic routes of Y101 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the collaboration between Medicinal Chemistry and Research active pharmaceutical ingredient (API), a fit for purpose route for the kilo scale synthesis of Y101 was developed. In contrast, the improved route described here did not require purification by column chromatography for all steps, and the formation of impurities was effectively suppressed. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of Y101.
Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry
Wagner, Michel,Ohlund, Leanne B.,Shiao, Tze Chieh,Vézina, Amélie,Annabi, Borhane,Roy, René,Sleno, Lekha
, p. 1632 - 1640 (2015/11/16)
Rationale An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light (12C6) and heavy (13C6) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. Methods Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. Results A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. Conclusions This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.
O-Tertiary amino-alkyl-N-benzoyl tyrosil amides
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, (2008/06/13)
Tyrosine derivatives of the formula: STR1 wherein: R1 is a linear or branched-chain alkyl group having 1-6 carbon atoms, terminating by a tertiary amino group; R 2 is an unsubstituted, monosubstituted or di-substituted phenyl or benzyloxy group, the substituent being --Cl, --Br, --NO2, --OCH3, --CH3 or --CF3 ; R3 is a primary, secondary or tertiary amino group or an aryl-alkylamino group having 7-9 carbon atoms; and salts of said tyrosine derivatives with pharmaceutically acceptable acids.
