28898-03-5Relevant articles and documents
Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors
Wang, Zhen,Shi, Jiantao,Zhu, Xianglong,Zhao, Wenwen,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Yajing,Ding, Shi,Liu, Ju,Chen, Ye
, (2020/10/21)
Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed excellent c-Met kinase activity in vitro, and IC50 values of ten compounds (23a, 23e, 23f, 23l, 23r, 23s, 23v, 23w, 23x and 23y) were less than 10.00 nM. Notably, three of them (23v, 23w and 23y) showed remarkable potency with IC50 values of 2.31 nM, 1.91 nM and 2.44 nM, respectively, and thus they were more potent than positive control drug foretinib (c-Met, IC50 = 2.53 nM). Cytotoxic evaluation indicated the most promising compound 23w showed remarkable cytotoxicity against A549, H460 and HT-29 cell lines with IC50 values of 1.57 μM, 0.94 μM and 0.65 μM, respectively. Furthermore, the acridine orange/ethidium bromide (AO/EB) staining, cell apoptosis assays by flow cytometry, wound-healing assays and transwell migration assays on HT-29 and/or A549 cells of 23w were performed. Especially compound 23w, which displayed potent antitumor, apoptosis induction and antimetastatic activity, could be used as a promising lead for further development. Meanwhile, their preliminary structure-activity relationships (SARs) were also discussed.
Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors
Liu, Ju,Yang, Di,Yang, Xiuxiu,Nie, Minhua,Wu, Guodong,Wang, Zhunchao,Li, Wei,Liu, Yajing,Gong, Ping
, p. 4475 - 4486 (2017/07/22)
A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90?nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0.06?μM, 0.05?μM, 0.18?μM, 0.023?μM and 0.66?μM, respectively, and thus it was 1.22- to 3.50-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.
Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modi?ed scaffold as potent antifungal agents
Zhang, Xiao-Xiao,Jin, Hong,Deng, Yuan-Jie,Gao, Xu-Heng,Li, Yong,Zhao, Yong-Tian,Tao, Ke,Hou, Tai-Ping
, p. 1731 - 1736 (2017/07/27)
Twenty-seven novel pyrazole carboxamides with diarylamine-modi?ed scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC50 values of 0.013, 1.608 and 1.874?μg/mL, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC50 value of 22.21?μg/mL. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.
Synthesis and in silico evaluation of novel compounds for PET-based investigations of the norepinephrine transporter
Neudorfer, Catharina,Seddik, Amir,Shanab, Karem,Jurik, Andreas,Rami-Mark, Christina,Holzer, Wolfgang,Ecker, Gerhard,Mitterhauser, Markus,Wadsak, Wolfgang,Spreitzer, Helmut
, p. 1712 - 1730 (2015/01/30)
Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz- ol-2-one (Me@APPI), this paper aims at the development of several fluorinated methylaminebased analogs of this compound. The newly synthesized compounds were computationally evaluated for their interactions with the monoamine transporters and represent reference compounds for PET-based investigation of the NET.
Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-Aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3 H)-yl]-1-(methylamino)butan-2- ols (WYE-103231)
O'Neill, David J.,Adedoyin, Adedayo,Alfinito, Peter D.,Bray, Jenifer A.,Cosmi, Scott,Deecher, Darlene C.,Fensome, Andrew,Harrison, Jim,Leventhal, Liza,Mann, Charles,McComas, Casey C.,Sullivan, Nicole R.,Spangler, Taylor B.,Uveges, Albert J.,Trybulski, Eugene J.,Whiteside, Garth T.,Zhang, Puwen
experimental part, p. 4511 - 4521 (2010/08/20)
Structural modification of a virtual screening hit led to the identification of a new series of 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol- 1(3H)-yl]-1-(methylamino)butan-2-ols which are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound S-17b (WYE-103231) had low nanomolar hNET potency (IC50 = 1.2 nM) and excellent selectivity for hNET over hSERT (>1600-fold) and hDAT (>600-fold). S-17b additionally had a good pharmacokinetic profile and demonstrated oral efficacy in rat models of ovariectomized-induced thermoregulatory dysfunction and morphine dependent flush as well as the hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain.
METHODS FOR THE PREPARATION OF HYDROXY-SUBSTITUTED ARYL SULFAMIDE COMPOUNDS
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Page/Page column 12, (2009/07/03)
The present invention is directed to processes for the preparation of hydroxy-substituted aryl sulfamide derivatives of the formula I or pharmaceutically acceptable salts, stereoisomers or tautomers thereof, which are monoamine reuptake inhibitors wherein
ARYL SULFAMIDE DERIVATIVES AND METHODS OF THEIR USE
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Page/Page column 95-96, (2008/12/06)
The present invention is directed to aryl sulfamide derivatives of formula (I): or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms, sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorders, cognitive disorders, diabetic neuropathy, pain, and other diseases or disorders.
Novel 1,5-benzodiazepines as CCK-B ligands. Effect of aryl-carbamic substituents at the C-3 position together with halogen substitution on the benzo-fused ring
Tranquillini, M. Elvira,Cassara, Paolo G.,Corsi, Mauro,Curotto, Giovanni,Donati, Daniele,Finizia, Gabriella,Pentassuglia, Giorgio,Polinelli, Stefano,Tarzia, Giorgio,Ursini, Antonella,Van Amsterdam, Franciscus T.M.
, p. 353 - 357 (2007/10/03)
The synthesis and biological evaluation as potential CCK-B receptor ligands of a number of 1-isopentyl-3-aryloxycarbamoyl-5-aryl-1,5-benzodiazepines substituted with halogen atoms on the benzo-fused ring is here briefly discussed.
