21416-43-3Relevant academic research and scientific papers
New insight into nucleo α-amino acids – Synthesis and SAR studies on cytotoxic activity of β-pyrimidine alanines
Bretner, Maria,Ignatowska, Jolanta,Karatsai, Olena,Mironiuk-Puchalska, Ewa,Wielechowska, Monika,Grze?kowiak, Piotr,Jolanta R?dowicz, Maria,Koszytkowska-Stawińska, Mariola,Wińska, Patrycja
, (2020/05/22)
Three series of the β-pyrimidine alanines, including willardiine - a naturally occurring amino acid, were prepared from the L-serine-derived sulfamidates. Compounds 3b, 4a and 4b demonstrated antiproliferative activity toward the studied cancer cell lines, albeit the effect of these compounds on human brain astrocytoma MOG-G-CCM cells was more significant than on human neuroblastoma SK-N-AS cells. The cytosine analog of willardiine, compound 4b, reduced viability of MOG-G-CCM cells with EC50 = 36 ± 2 μM, more effectively than AMPA antagonist GYKI 52466. Willardiine showed possible capability of affecting invasiveness of glioblastoma U251 MG cells with no effect on their viability and morphology. Compound 3d, the ethyl ester of willardiine, featured activity toward binding domain hHS1S2I of the GluR2 receptor. Docking analysis revealed that the location mode of compound 3d at the S1S2 domain of hGluR2 (PDB ID: 3R7X) might differ from that of willardiine.
Synthesis of Willardiine and 6-azawillardiine analogs: Pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes
Jane, David E.,Hoo, Ken,Kamboj, Raj,Deverill, Michele,Bleakman, David,Mandelzys, Allan
, p. 3645 - 3650 (2007/10/03)
Both willardiine and azawillardiine analogs (18-28) have been reported to be potent and selective agonists for either AMPA or kainate receptors. We report here the novel synthesis and pharmacological characterization of a range of willardiine (18-23) and 6-azawillardiine (24-28) analogs on cells individually expressing human homomeric hGluR1, hGluR2, hGluR4, or hGluR5 receptors. Reaction of the sodium salts of substituted uracils (7-12) or 6- azauracils (13-16) with (S)-3-[(tert-butoxycarbonyl)amino]oxetan-2-one (17) in dry DMF, subsequent deprotection in TFA, and purification by ion-exchange chromatography gave mainly the willardiine analog in which alkylation took place on N1 of the uracil ring. We have investigated the subtype selectivity of these compounds by examining their binding affinity for homomeric hGluR1, -2, -4, or -5 (and hGluR6 in the case of 5-iodowillardiine (22)). From this study we have demonstrated that 22 has high affinity for hGluR5 and, compared to kainate, displays excellent selectivity for this receptor over both the AMPA receptor subtypes and the homomeric kainate receptor, hGluR6. 5- Fluorowillardiine (19) has higher affinity than AMPA for both homomeric hGluR1 and hGluR2 and compared to AMPA displays greater selectivity for AMPA receptor subtypes over the kainate receptor, hGluR5. Some structural features required for optimal activity at homomeric AMPA or kainate receptor subtypes have also been identified. It would appear that quite large lipophilic substituents at the 5-position of the uracil ring not only are accommodated by hGluR5 receptors but also lead to enhanced affinity for these receptors. In contrast to this, for optimal binding affinity to hGluR1, -2, or -4, smaller, electron-withdrawing substituents are required. For optimal activity at hGluR4 receptors a 6-azasubstituted willardiine is favored. The subtype- selective compounds described here are likely to be useful tools to probe the distribution and the physiological roles of the various glutamate receptor subunits in the central nervous system.
BIOSYNTHESIS OF β-(1,2,4-TRIAZOL-1-YL)ALANINE IN HIGHER PLANTS
Ikegami, Fumio,Komada, Yumiko,Kobori, Masuko,Hawkins, Douglas R.,Murakoshi, Isamu
, p. 2507 - 2508 (2007/10/02)
β-(1,2,4-triazol-1-yl)Alanine, an important metabolite of the triazole-based fungicide Myclobutanil, was shown to be derived from O-acetyl-L-serine and 1,2,4-triazole by cysteine synthase in higher plants.Some properties of this enzyme in the biosynthesis of β-(1,2,4-triazol-1-yl)alanine are described.
Biomimetic Synyhesis of Heterocyclic β-Substituted Alanines by Pyridoxal 5'-Phosphate-Catalyzed Chemical Reactions
Murakoshi, Isamu,Ikegami, Fumio,Yoneda, Yoshihiro,Ihara, Harumi,Sakata, Kumiko,Koide, Chiharu
, p. 1473 - 1478 (2007/10/02)
Several heterocyclic β-substituted alanines were biomimetically synthesized by incubating 0.1M acetate buffer solution containing the appropriate heterocyclic compound and O-acetylserine or serine in the presence of pyridoxal 5'-phosphate (PLP) and metal ions.This PLP-catalyzed chemical reaction depends upon pH, metal ions and temperature.The addition of Ga3+, Fe3+ or Al3+ enhanced the rate of synthesis.The optimum of the various reaction conditions of this biomimetic method is described.Keywords - biomymetic synthesis; amino acid synthesis; heterocyclic β-substituted alanine; non-protein amino acid; O-acetylserine; N-heterocyclic compound; pyridoxal 5'-phosphate; metal ion
