2104-89-4Relevant articles and documents
Simultaneous determination of serine enantiomers in plasma using Mosher's reagent and stable isotope dilution gas chromatography-mass spectrometry
Hasegawa, Hiroshi,Shinohara, Yoshihiko,Masuda, Nami,Hashimoto, Takao,Ichida, Kimiyoshi
, p. 502 - 507 (2011)
D-Serine is a co-agonist of the N-methyl-D-aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D-serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D-serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC-MS with selected ion monitoring (GC-MS-SIM). DL-[2H3]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O-diacylation with optically active (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular-related ions of the epimers in the chemical ionization mode. The intra- and inter-day reproducibility of the assay was less than 5% for D-serine and 3% for L-serine. The method was successively applied to study the pharmacokinetics of D-serine in rats. Copyright
N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
, (2020/04/09)
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF ABNORMAL CELLULAR PROLIFERATION
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Page/Page column 127-128, (2019/07/20)
This invention is in the area of heterocyclic-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties
Zhou, Shaa,Zhou, Sha,Xie, Yongtao,Meng, Xiangde,Wang, Baolei,Xiong, Lixia,Yang, Na,Li, Zhengming
supporting information, p. 1254 - 1256 (2017/11/24)
Ryanodine receptors (RyRs) activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the D-alanine acid and D-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points, 1H NMR, 13C NMR, elemental analysis and specific optical rotation analysis. The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10 mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5 mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80% and 90% respectively at 0.0001 mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.
