120060-13-1Relevant articles and documents
Micromolecular non-nucleoside compound as immunomodulator
-
Paragraph 0237-0239; 0241; 0274-0277, (2021/06/09)
The invention discloses a structure, a preparation method and application of a micromolecular non-nucleoside targeted CD73 immunomodulator. The structure of the compound is shown as a general formula (I), and R1, R2, R3, R4, R5, X, Y and W groups are defined as in the claims. The compound acts on CD73 protein, blocks the interaction between the CD73 protein and a substrate of the CD73 protein, and can be used for preparing medicines and/or compositions for treating and/or diagnosing cancers, infectious diseases, autoimmune diseases and neurodegenerative diseases.
Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties
Yu, Jui-Yin,Cheng, Hsiu-Jung,Wu, Huei-Ru,Wu, Wei-Shen,Lu, Jui-Wen,Cheng, Ting-Jen,Wu, Ying-Ta,Fang, Jim-Min
, p. 729 - 741 (2018/03/26)
Transglycosylase (TGase) is essential to biosynthesis of peptidoglycan for formation of bacterial cell wall. Moenomycin is a potent TGase inhibitor, but not used in clinic treatment due to its poor pharmacokinetics. The E?F disaccharide, phosphoglycerate and lipid tail in moenomycin are crucial elements for TGase inhibition and antibacterial activity. Based on this scaffold, a series of truncated mimics comprising biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties were designed to test their TGase inhibitory activity. In this design, the phosphorylpropanoate group is a surrogate of phosphoglycerate with improved stability. A library of lipid tails can be constructed by a straightforward approach using Cu(I)-catalyzed (3 + 2) cycloaddition reactions, and the as-synthesized triazole ring can provide additional hydrogen bonds in the TGase active site. Our molecular docking experiments reveal that the biphenyl group provides π–π and π–cation interactions to act as a simplified alternative of the C–E disaccharide in moenomycin. To play the role of the oxonium transition state in transglycosylation, the amine linker exists as a positively charged species in physiological condition to attain electrostatic interactions with acidic residues. In this study, two biphenyl-linked 2-alkoxy-3-phosphorylpropanoate compounds (8 and 10) are found to exhibit modest inhibitory activity (IC50 ≈ 150 μM) against the TGase of Acinetobacter baumannii and good antibacterial activity against Staphylococcus aureus (MIC = 6.3 μM).
THERAPEUTIC MACROLIDE COMPOUNDS AND THEIR USE
-
Page/Page column 90, 91, (2010/06/17)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain macrolide compounds (for convenience, collectively referred to herein as "MC compounds"), which, inter alia, are useful in treatment of cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to treat proliferative conditions such as cancer, and in the treatment of diseases and conditions that are mediated by the regulation (e.g. inhibition) of cell proliferation, optionally in combination with another agent.
Syntheses of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones: Intermediates in the synthesis of aprepitant
Nelson, Todd D.,Rosen, Jonathan D.,Brands, Karel M.J.,Craig, Bridgette,Huffman, Mark A.,McNamara, James M.
, p. 8917 - 8920 (2007/10/03)
The preparation of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones from N-substituted β-amino alcohols is reported. These were useful intermediates in the synthesis and development of aprepitant.