25492-69-7Relevant academic research and scientific papers
Development of Potent and Selective Antagonists for the UTP-Activated P2Y4 Receptor
Rafehi, Muhammad,Malik, Enas M.,Neumann, Alexander,Abdelrahman, Aliaa,Hanck, Theodor,Namasivayam, Vigneshwaran,Müller, Christa E.,Baqi, Younis
, p. 3020 - 3038 (2017/04/21)
P2Y4 is a Gq protein-coupled receptor activated by uridine-5′-triphosphate (UTP), which is widely expressed in the body, e.g., in intestine, heart, and brain. No selective P2Y4 receptor antagonist has been described so far. Therefore, we developed and optimized P2Y4 receptor antagonists based on an anthraquinone scaffold. Potency was assessed by a fluorescence-based assay measuring inhibition of UTP-induced intracellular calcium release in 1321N1 astrocytoma cells stably transfected with the human P2Y4 receptor. The most potent compound of the present series, sodium 1-amino-4-[4-(2,4-dimethylphenylthio)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (PSB-16133, 61) exhibited an IC50 value of 233 nM, selectivity versus other P2Y receptor subtypes, and is thought to act as an allosteric antagonist. A receptor homology model was built and docking studies were performed to analyze ligand-receptor interactions. Compound 64 (PSB-1699, sodium 1-amino-4-[4-(3-pyridin-3-ylmethylthio)phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate) represents the most selective P2Y4 receptor antagonist known to date. Compounds 61 and 64 are therefore anticipated to become useful tools for studying this scarcely investigated receptor.
Development of 1-Amino-4-(phenylamino)anthraquinone-2-sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL-Induced Osteoclastogenesis
Lee, Chia-Chung,Chen, Chun-Liang,Liu, Fei-Lan,Chiou, Chung-Yu,Chen, Tsung-Chih,Wu, Cheng-Chi,Sun, Wei-Hsin,Chang, Deh-Ming,Huang, Hsu-Shan
, p. 342 - 355 (2016/05/19)
A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds was not a result of their cytotoxicity. Further, the inhibitory activities of compounds LCCY-13 and LCCY-15 were further confirmed by including specific inhibition of NFATc1 expression levels in nuclei using an immunofluorescent analysis. In addition, LCCY-13 and LCCY-15 also significantly attenuated the bone resorption activity of osteoclasts according to a pit formation assay. Thus, a new class of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium compounds might be considered as an essential lead structure for the further development of anti-resorptive agents.
Development of potent and selective inhibitors of ecto-5′- nucleotidase based on an anthraquinone scaffold
Baqi, Younis,Lee, Sang-Yong,Iqbal, Jamshed,Ripphausen, Peter,Lehr, Anne,Scheiff, Anja B.,Zimmennann, Herbert,Bajorath, Jürgen,Müller, Christa E.
experimental part, p. 2076 - 2086 (2010/08/19)
ecto-5′-Nucleotidase (eN, CD73) plays a major role in controlling extracellular adenosine levels. eN inhibitors have potential as novel drugs, for example, for the treatment of cancer. In the present study, we synthesized and investigated a series of 55 anthraquinone derivatives as potential inhibitors of eN, 11 of which are novel compounds and another 11 of which had previously been described but have now been synthesized by an improved method. We identified several potent inhibitors of rat eN. The most potent compounds were l-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2- sulfonate (45, PSB-0952, K1 = 260 nM) and 1-amino-4-[2- anthracenylamino]-9,10-dioxo-9,10dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most potent eN inhibitor described to date. Selected compounds were further characterized and found to exhibit a competitive mechanism of inhibition. Investigations of ecio-nucleoside triphosphate diphosphohydrolases (NTPDases) and the P2Y receptor subtypes P2Y2, P2Y4, P2Y6, and P2Y12 showed that compound 45 exhibited the highest degree of selectivity ( > 150-fold).
Combinatorial synthesis of anilinoanthraquinone derivatives and evaluation as non-nucleotide-derived P2Y2 receptor antagonists
Weyler, Stefanie,Baqi, Younis,Hillmann, Petra,Kaulich, Marko,Hunder, Andrea M.,Mueller, Ingrid A.,Mueller, Christa E.
, p. 223 - 227 (2008/09/19)
A library of anilinoanthraquinone derivatives was synthesized by parallel Ullmann coupling reaction of bromaminic acid with aniline derivatives in solution using a compact parallel synthesizer. The products were purified by HPLC and evaluated as antagonists at mouse and human P2Y2 receptors. 4-Phenylamino-substituted 1-amino-2-sulfoanthraquinones, for example, 1-amino-4-(2-methoxyphenyl)-2-sulfoanthraquinone (PSB-716), were potent P2Y2 antagonists with IC50 values in the low micromolar range.
