13195-66-9Relevant academic research and scientific papers
π-Conjugated polymers with pendant coumarins: Design, synthesis, characterization, and interactions with carbon nanotubes
Imit, Mokhtar,Imin, Patigul,Adronov, Alex
, p. 759 - 768 (2016)
A series of new fluorene-based π-conjugated polymers having coumarin derivatives as part of dendritic side chains were designed and prepared using the Suzuki-Miyaura cross-coupling reaction. A new coumarin derivative bearing a heptyl side chain for solubility was utilized to ensure solubility of the final polymers. It was found that fluorescence resonance energy transfer (FRET) from the coumrains to the polyfluorene backbone was efficient, especially for the polymers decorated with lower-generation dendrons. Each of the polymers was found to interact strongly with the surface of single-walled carbon nanotubes (SWNTs) in THF, and their ability to selectively disperse specific SWNT chiralities was investigated. Photoluminescence studies revealed that the strong polymer emission is efficiently quenched in the corresponding supramolecular complexes with SWNTs. This high quenching efficiency indicates that the coumarin-polymer FRET system can be supramolecularly bound to the surface of (SWNTs to produce an energy transfer system in which the energy absorbed by the donor coumarin chromophores is channeled to the SWNTs.
Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists
Liu, Yang,Zhang, Qing,Chen, Lin-Hai,Yang, Hui,Lu, Wei,Xie, Xin,Nan, Fa-Jun
, p. 579 - 583 (2016)
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.
A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation
Galleano, Iacopo,Schiedel, Matthias,Jung, Manfred,Madsen, Andreas S.,Olsen, Christian A.
, p. 1021 - 1031 (2016)
Sirtuins are important regulators of lysine acylation, which is implicated in cellular metabolism and transcriptional control. This makes the sirtuin class of enzymes interesting targets for development of small molecule probes with pharmaceutical potential. To achieve detailed profiling and kinetic insight regarding sirtuin inhibitors, it is important to have access to efficient assays. In this work, we report readily synthesized fluorogenic substrates enabling enzyme-economical evaluation of SIRT2 inhibitors in a continuous assay format as well as evaluation of the properties of SIRT2 as a long chain deacylase enzyme. Novel enzymatic activities of SIRT2 were thus established in vitro, which warrant further investigation, and two known inhibitors, suramin and SirReal2, were profiled against substrates containing ε-N-acyllysine modifications of varying length.
Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters
Chen, Jiajia,Joseph, Devaneyan,Xia, Yuanzhi,Lee, Sunwoo
, p. 5943 - 5953 (2021/04/02)
Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method
Synthetic Scope of Br?nsted Acid-Catalyzed Reactions of Carbonyl Compounds and Ethyl Diazoacetate
Rahaman, Mizzanoor,Ali, M. Shahnawaz,Jahan, Khorshada,Hinz, Damon,Belayet, Jawad Bin,Majinski, Ryan,Hossain, M. Mahmun
, p. 6138 - 6147 (2021/05/06)
The comprehensive study of the reactions of carbonyl compounds and ethyl diazoacetate in the presence of a Br?nsted acid catalyst is described. In result, a broad range of 3-oxo-esters were synthesized from a variety of ketones and aliphatic aldehydes by 1,2-aryl/alkyl/hydride shift. Aryl-methyl ketones produced only aryl-migrated products, whereas other ketones yielded a mixture of products. For diaryl ketones, the identity of two inseparable migrated products was confirmed by two-dimensional NMR spectroscopy.
Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5
Ortiz Zacarías, Natalia V.,Van Veldhoven, Jacobus P. D.,Den Hollander, Lisa S.,Dogan, Burak,Openy, Joseph,Hsiao, Ya-Yun,Lenselink, Eelke B.,Heitman, Laura H.,Ijzerman, Adriaan P.
, p. 11035 - 11053 (2019/12/24)
CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the highly conserved intracellular binding site in chemokine receptors provides a new avenue for the design of multitarget ligands. In this study, we synthesized and evaluated the biological activity of a series of triazolopyrimidinone derivatives in CCR2 and CCR5. Radioligand binding assays first showed that they bind to the intracellular site of CCR2, and in combination with functional assays on CCR5, we explored structure-affinity/activity relationships in both receptors. Although most compounds were CCR2-selective, 39 and 43 inhibited β-arrestin recruitment in CCR5 with high potency. Moreover, these compounds displayed an insurmountable mechanism of inhibition in both receptors, which holds promise for improved efficacy in inflammatory diseases.
Screening, synthesis, crystal structure, and molecular basis of 6-amino-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles as novel AKR1C3 inhibitors
Zheng, Xuehua,Jiang, Zan,Li, Xiaolin,Zhang, Chen,Li, Zhe,Wu, Yinuo,Wang, Xinhua,Zhang, Chao,Luo, Hai-bin,Xu, Jun,Wu, Deyan
supporting information, p. 5934 - 5943 (2018/11/23)
AKR1C3 is a promising therapeutic target for castration-resistant prostate cancer. Herein, an evaluation of in-house library discovered substituted pyranopyrazole as a novel scaffold for AKR1C3 inhibitors. Preliminary SAR exploration identified its derivative 19d as the most promising compound with an IC50 of 0.160 μM among the 23 synthesized molecules. Crystal structure studies revealed that the binding mode of the pyranopyrazole scaffold is different from the current inhibitors. Hydroxyl, methoxy and nitro group at the C4-phenyl substituent together anchor the inhibitor to the oxyanion site, while the core of the scaffold dramatically enlarges but partially occupies the SP pockets with abundant hydrogen bond interactions. Strikingly, the inhibitor undergoes a conformational change to fit AKR1C3 and its homologous protein AKR1C1. Our results suggested that conformational changes of the receptor and the inhibitor should both be considered during the rational design of selective AKR1C3 inhibitors. Detailed binding features obtained from molecular dynamics simulations helped to finally elucidate the molecular basis of 6-amino-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles as AKR1C3 inhibitors, which would facilitate the future rational inhibitor design and structural optimization.
Auto-Tandem Catalysis-Induced Synthesis of Trisubstituted Furans through Domino Acid-Acid-Catalyzed Reaction of Aliphatic Aldehydes and 1,3-Dicarbonyl Compounds by using N-Bromosuccinimide as Oxidant
Huang, Wenbo,Liu, Changhui,Gu, Yanlong
supporting information, p. 1811 - 1818 (2017/06/09)
A simple aluminium(III) chloride-catalyzed synthesis of tri-substituted furans from aliphatic aldehydes and 1,3-dicarbonyl compounds was developed by using N-bromosuccinimide (NBS) as an oxidant. This method was effective for the synthesis of various furan derivatives. Some of the products were not accessible with the previously reported methods. Mechanically, this reaction involved an auto-tandem catalysis based on a newly reported acid-acid-catalyzed tandem reaction to ensure that furans were successfully synthesized. (Figure presented.).
From in vitro to in cellulo: Structure-activity relationship of (2-nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa
Storz, Michael P.,Allegretta, Giuseppe,Kirsch, Benjamin,Empting, Martin,Hartmann, Rolf W.
supporting information, p. 6094 - 6104 (2014/08/05)
Recent studies have shown that compounds based on a (2-nitrophenyl)methanol scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The most promising molecule displayed anti-biofilm activity and a tight-binding mode of action. Herein, we report on the convenient synthesis and biochemical evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The in vitro potency of these inhibitors against recombinant PqsD as well as the effect of selected compounds on the production of the signal molecules HHQ and PQS in P. aeruginosa were examined. The gathered data allowed the establishment of a structure-activity relationship, which was used to design fluorescent inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol derivatives with improved in cellulo efficacy providing new perspectives towards the application of PqsD inhibitors as anti-infectives. This journal is the Partner Organisations 2014.
