91806-09-6Relevant 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.
INHIBITING CONNEXIN 46 TO TREAT GLIOBLASTOMA AND OTHER CONDITIONS
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Page/Page column 28, (2019/04/16)
Provided herein are compositions, systems, kits, and methods for treating a disease or condition by administering to a subject an agent that inhibits connexin 46 (Cx46) (e.g., ondancetron, an ondancetron analog or derivative, testosterone, a testosterone
One-pot propagation of (Hetero)Arylamines: Modular synthesis of diverse Amino-di(hetero)arylamines
Liang, Xueting,Xu, Liang,Li, Cuihua,Jia, Xin,Wei, Yu
, p. 721 - 731 (2019/01/08)
Formal propagation of (hetero)arylamine is achieved via a one-pot Buchwald–Hartwig C–N cross-coupling and nitro reduction sequence, enabling a rapid modular synthesis of diverse amino-di(hetero)arylamines from (hetero)arylamines and halogenated nitrobenzenes. Various functionalized aromatic amines with different electronic and steric environments can be efficiently prolongated to formally incorporate another arylamino fragments. This approach has been successfully applied in the synthesis of more than forty amino-di(hetero)arylamines. The applicability of this method has also been demonstrated in the synthesis of oligoanilines and the tyrosine-kinase inhibitor Imatinib.
Design, synthesis, and structure-activity relationships of novel imidazo[4,5-c]pyridine derivatives as potent non-nucleoside inhibitors of hepatitis C virus NS5B
Liu, Moyi,Xu, Qiaoling,Guo, Su,Zuo, Ruixi,Hong, Yue,Luo, Yong,Li, Yingxiu,Gong, Ping,Liu, Yajing
, p. 2621 - 2631 (2018/04/30)
The hepatitis C virus (HCV) NS5B polymerase is an attractive target for the development of novel and selective inhibitors of HCV replication. In this paper, the design, synthesis, and preliminary SAR studies of novel inhibitors of HCV NS5B polymerase based on the structure of tegobuvir have been described. The efforts to optimize the antiviral potency and reduce the treatment side effects with respect to genotype 1b resulted in the discovery of compound 3, which exhibited an EC50 of 1.163 nM and a CC50 >200 nM in a cell-based HCV replicon system assay. Additionally, testing for inhibition of the hERG channel showed a marked improvement over tegobuvir and the pharmacokinetic properties of compound 3 indicated that it was worthy of further investigation as a non-nucleoside inhibitor of HCV NS5B polymerase.
Method for synthesizing diarylamine by optical/nickel concerted catalysis
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Paragraph 0046; 0047; 0048; 0049; 0124; 0125; 0126; 0127, (2018/09/08)
The invention discloses a method for synthesizing diarylamine by optical/nickel concerted catalysis. According to the method, a ligand does not need to be added, and simple and cheap nickel salt is directly used as a metal catalyst to cooperate with a photosensitizer to catalyze arylamine and aryl bromide to generate cross-coupling. The method has the following advantages: (1) the use amount of BODIPY type organic photocatalyst is low, and the BODIPY type organic photocatalyst has a better catalysis effect in comparison with metal iridium and ruthenium photocatalysts reported in the literature; (2) the BODIPY type organic photocatalyst is easy for synthesis; (3) the use amount of nickel salt is few, and the ligand does not need to be added; and (4) the reaction conditions are mild, and theyield of most coupling products is higher than 90%. According to the method disclosed by the invention, high temperature and high pressure equipment is not needed, temperature change scope is small,experimental procedure is simple and easy to operate, and the method has a relatively high application value and industrial popularization potential.
Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids
Wang, Hongyu,Gao, Xuheng,Zhang, Xiaoxiao,Jin, Hong,Tao, Ke,Hou, Taiping
, p. 90 - 93 (2016/12/09)
Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC50= 1.71 mg/L) and lead fungicide fenfuram (EC50= 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.
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.
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.
The 4.4′-benzidine rearrangement of 4-alkyl substituted hydrazobenzenes
Bouillon, Marc E.,Meyer, Hartmut H.
, p. 3151 - 3161 (2016/05/24)
When treated with dilute inorganic acids N,N′-diarylhydrazines (hydrazobenzenes) with an alkyl substituent in the 4-position undergo [5,5]-sigmatropic rearrangement reactions to furnish 4-(4′-aminophenyl)-4-alkylcyclohexa-2,5-dienimines (ipso-benzidines) in moderate to excellent yields. Steric bulk of the 4-alkyl substituent in the starting material decreases the yield of the respective ipso-benzidine. Additional electron-donating alkyl substituents in the ortho- and/or meta-positions on both rings generally promote the reaction and consequently increase the yield of the 4.4′-benzidine rearrangement product. Described herein are our findings regarding the scope and limits of this unusual benzidine rearrangement.
"All-water" one-pot diverse synthesis of 1,2-disubstituted benzimidazoles: Hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' by water
Kommi, Damodara N.,Jadhavar, Pradeep S.,Kumar, Dinesh,Chakraborti, Asit K.
, p. 798 - 810 (2013/04/24)
A new "all-water" tandem arylaminoarylation/arylaminoalkylation- reduction-cyclisation route is reported for one-pot diversity oriented synthesis of regiodefined 1,2-disubstituted benzimidazoles. Water plays a crucial and indispensable role through hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' in the formation of N-mono-aryl/aryl alkyl/alkyl/cycloalkyl o-nitroanilines under metal and base-free conditions to replace the transition metal-based C-N bond formation (aryl amination) chemistry and underlines the origin of regiodefined installation of the diverse selection of aryl, aryl alkyl, and alkyl/cycloalkyl groups as substituents on the benzimidazole scaffold to form the 1,2-disubstituted benzimidazoles. The influence of the hydrogen bond effect of water in promoting the arylaminoarylation reaction under base and metal-free conditions has been realized through observation of inferior yields in D2O compared to that obtained in water during the reaction of o-fluoronitrobenzene with aniline separately performed in water and D2O under similar experimental conditions. Water also provides assistance in promoting the subsequent nitro reduction and in the final cyclocondensation steps. The role of water in promoting the cyclocondensation reaction through hydrogen bonds is realized by the differential product yields during the reaction of mono-N-phenyl-o- phenylenediamine with benzaldehyde performed separately in water and D 2O. The better hydrogen bond donor and hydrogen bond acceptor abilities of water compared to those of the organic solvents are the contributing/deciding factors for making the new water-assisted tandem arylaminoarylation/arylaminoalkylation-reduction-cyclisation strategy for the diversified synthesis of the regiodefined 1,2-disubstituted benzimidazoles effective in an aqueous medium, making it represent a true "all-water chemistry."
