The title pyrimidine derivative, C(18)H(21)N(3)O(6), was obtained by the reaction of methyl 2-[2-(benzyl-oxycarbon-yl)amino-propan-2-yl]-5-hy-droxy-6-oxo-1,6-dihydro-pyrimidine-4-carboxyl-ate with dimethyl sulfate in dimethyl sulfoxide. The mol-ecule has a V-shaped structure, the phenyl and the pyrimidine rings making a dihedral angle of 43.1 (1)°. The methyl group substituting the pyrimidine ring deviates slightly from the ring mean-plane [C-N-C-C torsion angle = 5.49 (15)°], and the methyl ester substituent has a conformation suitable for the formation of an intra-molecular O-H⋯O hydrogen bond with the hydroxyl functionality. In the crystal, molecules are linked into chains along the b axis by N-H⋯O hydrogen bonds.
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http://dx.doi.org/10.1107/S160053681204233X | DOI Listing |
Genes Genomics
January 2025
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
Background: The clinical course of high-risk neuroblastoma patients remains suboptimal, and the dynamic and reversible nature of cellular senescence provides an opportunity to develop new therapies.
Objective: This study aims to identify unique markers of cellular senescence in neuroblastoma and to explore their clinical significance.
Methods: The impact of multiple genetic regulatory mechanisms on cellular senescence-associated genes (CSAGs) was first assessed.
Br J Anaesth
January 2025
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:
Background: Chronic neuropathic pain generally has a poor response to treatment with conventional drugs. Sympathectomy can alleviate neuropathic pain in some patients, suggesting that abnormal sympathetic-somatosensory signaling interactions might underlie some forms of neuropathic pain. The molecular mechanisms underlying sympathetic-somatosensory interactions in neuropathic pain remain obscure.
View Article and Find Full Text PDFAJNR Am J Neuroradiol
January 2025
From the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland.
Background And Purpose: Whether differences in the O-methylguanine-DNA methyltransferase () promoter methylation status of glioblastoma (GBM) are reflected in MRI markers remains largely unknown. In this work, we analyze the ADC in the perienhancing infiltration zone of GBM according to the corresponding status by using a novel distance-resolved 3D evaluation.
Materials And Methods: One hundred one patients with wild-type GBM were retrospectively analyzed.
J Immunother Cancer
January 2025
Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS/INSERM/UNISTRA, Illkirch-Graffenstaden, France
Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.
Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial.
J Med Chem
January 2025
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i., Prague 160 00, Czech Republic.
Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.
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