55377-84-9Relevant academic research and scientific papers
Discovery of (5-Phenylfuran-2-yl)Methanamine derivatives as new human sirtuin 2 Inhibitors
Wang, Lijiao,Li, Chao,Chen, Wei,Song, Chen,Zhang, Xing,Yang, Fan,Wang, Chen,Zhang, Yuanyuan,Qian, Shan,Wang, Zhouyu,Yang, Lingling
, (2019/08/07)
Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl) furan-2-yl)benzoic acid (20), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound 25 with an IC50 value of 2.47 μM, which is more potent than AGK2 (IC50 = 17.75 μM). Meanwhile, 25 likely possesses better water solubility (cLogP = 1.63 and cLogS = ?3.63). Finally, the molecular docking analyses indicated that 25 fitted well with the induced hydrophobic pocket of SIRT2.
Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties
Staroń, Jakub,Kurczab, Rafa?,Warszycki, Dawid,Sata?a, Grzegorz,Krawczyk, Martyna,Bugno, Ryszard,Lenda, Tomasz,Popik, Piotr,Hogendorf, Adam S.,Hogendorf, Agata,Dubiel, Krzysztof,Mat?oka, Miko?aj,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Wieczorek, Maciej,Zajdel, Pawe?,Bojarski, Andrzej J.
supporting information, (2019/11/28)
A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (1, 5-HT6R Ki = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R Ki = 25, 5-HT2AR Ki = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with pro-cognitive properties.
Mono- and biscouplings using triarylbismuths for the atom-efficient arylations of functionalized furans under palladium catalysis
Rao, Maddali L. N.,Awasthi, Dheeraj K.,Talode, Jalindar B.
supporting information; experimental part, p. 1907 - 1912 (2012/09/22)
Palladium-catalyzed cross-coupling reactions of functionalized bromofurans with triarylbismuths have been described for the atom-economic synthesis of functionalized arylfuran systems. The coupling reactions using triarylbismuths with various 2-bromofurans and 2,5-dibromofuran underwent smoothly to afford the corresponding 2-arylfurans and 2,5-diarylfurans in high yields in a short reaction time (one hour). Georg Thieme Verlag Stuttgart · New York.
Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization
Kong, Xiangqian,Qin, Jie,Li, Zeng,Vultur, Adina,Tong, Linjiang,Feng, Enguang,Rajan, Geena,Liu, Shien,Lu, Junyan,Liang, Zhongjie,Zheng, Mingyue,Zhu, Weiliang,Jiang, Hualiang,Herlyn, Meenhard,Liu, Hong,Marmorstein, Ronen,Luo, Cheng
experimental part, p. 7402 - 7417 (2012/10/08)
Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC 50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC 50 values with selectivity for B-RafV600Ein vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells.
BROAD SPECTRUM ANTIVIRAL AND ANTIPARASITIC AGENTS
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Page/Page column 42, (2011/11/01)
The invention provides compounds represented by the formulae: (I) and (II) where the compounds are useful in treating, for example, viral and/or parasitic infections. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds.
Synthesis and evaluation of compounds that induce readthrough of premature termination codons
Jung, Michael E.,Ku, Jin-Mo,Du, Liutao,Hu, Hailiang,Gatti, Richard A.
supporting information; experimental part, p. 5842 - 5848 (2011/10/18)
A structure-activity relationship (SAR) study was carried out to identify novel, small molecular weight compounds which induce readthrough of premature termination codons. In particular, analogs of RTC13, 1, were evaluated. In addition, hypothesizing that these compounds exhibit their activity by binding to the ribosome, we prepared the hybrid analogs 13 containing pyrimidine bases and these also showed good readthrough activity.
Gold catalysis: Desymmetrization in the furan-yne reaction
Hashmi, A. Stephen K.,Woelfle, Michael,Ata, Filiz,Frey, Wolfgang,Rominger, Frank
experimental part, p. 2297 - 2307 (2010/08/21)
A series of seven symmetric difuryl-diynes were synthesized by a route delivering an anti-configurated product as the major product. The gold-catalyzed conversion of the individual anti- and syn-diastereomers was investigated. The anti-diastereomer in a desymmetrization reaction chemoselectively delivered dihydroindenediols with a furyl and a 2-oxopropyl side chain. The syn-diastereomer was completely converted into oligomeric/polymeric material. Thus, it was not necessary to separate the minor amount of the syn-diastereomers from the product mixtures in order to isolate the dihydroindenediols. Georg Thieme Verlag Stuttgart - New York.
Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase γ
Pomel, Vincent,Klicic, Jasna,Covini, David,Church, Dennis D.,Shaw, Jeffrey P.,Roulin, Karen,Burgat-Charvillon, Fabienne,Valognes, Delphine,Camps, Montserrat,Chabert, Christian,Gillieron, Corinne,Fran?on, Bernard,Perrin, Dominique,Leroy, Didier,Gretener, Denise,Nichols, Anthony,Vitte, Pierre Alain,Carboni, Susanna,Rommel, Christian,Schwarz, Matthias K.,Rückle, Thomas
, p. 3857 - 3871 (2007/10/03)
Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kγ, have become attractive drug targets for inflammatory and autoimmune diseases. Here, we disclose a novel series of furan-2-ylmethylene thiazolidinediones as selective, ATP-competitive PI3Kγ i
Dantrolene analogues revisited: General synthesis and specific functions capable of discriminating two kinds of Ca2+ release from sarcoplasmic reticulum of mouse skeletal muscle
Hosoya, Takamitsu,Aoyama, Hiroshi,Ikemoto, Takaaki,Kihara, Yasutaka,Hiramatsu, Toshiyuki,Endo, Makoto,Suzuki, Masaaki
, p. 663 - 673 (2007/10/03)
The general synthesis of dantrolene analogues with various substituents on its phenyl ring has been developed via palladium-catalyzed cross-coupling reactions, the Stille or Suzuki reaction, as the key step. The effects of synthesized analogues have been evaluated by two kinds of Ca2+ release modes from sarcoplasmic reticulum (SR) of mouse skeletal muscle fibers based on: (1) the measurement of twitch contraction caused by the physiological Ca2+ release (PCR) of intact skeletal muscle and (2) the rate of Ca2+-induced Ca2+ release (CICR) in saponin-treated skinned muscle fibers. Although dantrolene, a lead compound, inhibits both twitch contraction and CICR, some structurally modified analogues exhibit one or the other of these effects. The methoxy congener, GIF-0185, potently inhibits the twitch contraction without affecting the CICR, while GIF-0166 and GIF-0248, the ortho-nitro regioisomer and ortho, ortho-dinitro substituted analogues, respectively, doubly potentiate the CICR exclusively.
Preparation of 5-aryl furfurals and aryl thiophene-2-carboxaldehydes via palladium-catalyzed C-C bond formation in aqueous media
Bussolari, Jacqueline C.,Rehborn, Diana C.
, p. 965 - 967 (2008/02/09)
(matrix presented) A series of 5-aryl furfurals and aryl thiophene-2-carboxaldehydes was synthesized. To this end, efficient and effective palladium-catalyzed C-C bond-forming reactions were carried out at room temperature in aqueous media. This mild proc
