229028-10-8Relevant articles and documents
[18F]fluoroethyltriazolyl monocyclam derivatives as imaging probes for the chemokine receptor CXCR4
Amor-Coarasa, Alejandro,Kelly, James M.,Singh, Pradeep K.,Ponnala, Shashikanth,Nikolopoulou, Anastasia,Williams, Clarence,Vedvyas, Yogindra,Jin, Moonsoo M.,David Warren,Babich, John W.
supporting information, (2019/05/01)
Determining chemokine receptor CXCR4 expression is significant in multiple diseases due to its role in promoting inflammation, cell migration and tumorigenesis. [68Ga]Pentixafor is a promising ligand for imaging CXCR4 expression in multiple tumor types, but its utility is limited by the physical properties of 68Ga. We screened a library of >200 fluorine-containing structural derivatives of AMD-3465 to identify promising candidates for in vivo imaging of CXCR4 expression by positron emission tomography (PET). Compounds containing fluoroethyltriazoles consistently achieved higher docking scores. Six of these higher scoring compounds were radiolabeled by click chemistry and evaluated in PC3-CXCR4 cells and BALB/c mice bearing bilateral PC3-WT and PC3-CXCR4 xenograft tumors. The apparent CXCR4 affinity of the ligands was relatively low, but tumor uptake was CXCR4-specific. The tumor uptake of [18F]RPS-534 (7.2 ± 0.3 %ID/g) and [18F]RPS-547 (3.1 ± 0.5 %ID/g) at 1 h p.i. was highest, leading to high tumor-to-blood, tumor-to-muscle, and tumor-to-lung ratios. Total cell-associated activity better predicted in vivo tumor uptake than did the docking score or apparent CXCR4 affinity. By this metric, and on the basis of their high yielding radiosynthesis, high tumor uptake, and good contrast to background, [18F]RPS-547, and especially [18F]RPS-534, are promising 18F-labeled candidates for imaging CXCR4 expression.
Deuterated acetylene derivatives, its pharmaceutical composition and application
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Paragraph 0270; 0271; 0272; 0273, (2018/11/22)
The invention discloses a deuterated acetylenic derivative, a pharmaceutical composition and application thereof. The deuterated acetylenic derivative comprises one or more of the deuterated acetylenic derivative (I) with curative effective dose, pharmace
HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS AND COMBINATIONS THEREOF
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Page/Page column 107, (2015/07/07)
Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by disregulation of a fatty acid synthase pathway by the administration of such compounds and combinations of such compounds and other therapeutic agents.
HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS
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Page/Page column 92, (2014/01/18)
Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by disregulation of a fatty acid synthase pathway by the administration of such compounds.
Coupling reactions of ortho-substituted halobenzenes with alkynes. The synthesis of phenylacetylenes and symmetrical or unsymmetrical 1,2-diphenylacetylenes
Stara, Irena G.,Stary, Ivo,Kollarovic, Adrian,Teply, Filip,Saman, David,Fiedler, Pavel
, p. 649 - 672 (2007/10/03)
The Pd- or Pd/Cu-catalyzed coupling reactions of halobenzenes bearing the methyl, hydroxymethyl, acetoxymethyl, methoxycarbonyl, or both methoxy and 4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl groups in the ortho-position with gaseous or metallated acetylene, (trialkylsilyl)acetylenes, and arylacetylenes have been systematically studied. Various functionalized aryl- or diarylacetylenes have been synthesized in good to excellent yields. Whereas additional fluoro, nitro, or methoxy group attached to the benzene ring does not interfere in the coupling reactions, the presence of a methoxycarbonyl requires a careful optimization of reaction conditions to achieve moderate yields.