130-00-7Relevant articles and documents
A missing relative: A Hoveyda-Grubbs metathesis catalyst bearing a peri-substituted naphthalene framework
Barbasiewicz, Michal,Grudzien, Krzysztof,Malinska, Maura
, p. 3171 - 3177 (2012)
Molecular scaffolds of polycyclic aromatic hydrocarbons can serve as unique tools to control the molecular and electronic structure of coordination compounds. Herein, we report the synthesis and properties of a Hoveyda-Grubbs metathesis catalyst bearing a chelating benzylidene ligand assembled on peri-substituted naphthalene. In contrast to other reported naphthalene-based complexes (Barbasiewicz, M. and Grela, K.Chem. Eur. J. 2008, 14, 9330-9337), it exhibits a very fast initiation behavior, attributed to a distorted molecular structure and reduced π-electron delocalization within the chelate ring.
Synthesis and biological evaluation of a benz[cd]indol-2(1H)-one derivatives
Nie, Jing,Dong, Dan-Dan,Zhang, Yan,Wang, Tai-Yi,Liu, Wei,Yi, Shou-Zhi
, p. 7329 - 7336 (2014)
Virtual screening of a library of 6.4 million compounds versus the structure of Xenopus Laevis' Aurora B kinase identified 1-(n-propyl)-6-[2-(carboxyl)tetrahydropyrrol-1-yl]sulfonyl-benzo[cd]indol-2(1H)-one 1 as a possible lead compound. Then, a novel series of benz[cd]indol-2(1H)-one derivatives were synthesized and evaluated as Aurora B kinase inhibitors. The structures of the synthetic compounds were confirmed by 1H NMR, IR, mass spectrometry and elemental analysis. These compounds were evaluated by in vitro enzyme assay using spectrophotometry. Among them, compound 7e displayed potent antitumor activity against Aurora B kinase.
Palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamines with alkyl chloroformates
Shi, Yaqi,Wu, Yangjie,Yang, Fan
, p. 4628 - 4637 (2020)
A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine derivatives with alkyl chloroformates has been developed, exhibiting broad functional group tolerance, high regioselectivity, and oxidant-free conditions. Furthermore, the reaction features its ease of further functionalization and transformation. For example, the concise synthesis of one BET bromodomain inhibitor was accomplished via benz[cd]indol-2(1H)-one after multistep transformations from the obtained alkoxycarbonylation product. In addition, the control experiments suggest that the reaction might involve a radical process and the C-H bond cleavage might not be involved in the rate-determining step.
RhIII-Catalyzed Double Dehydrogenative Coupling of Free 1-Naphthylamines with α,β-Unsaturated Esters
Rej, Supriya,Chatani, Naoto
, p. 11093 - 11098 (2020)
The RhIII-catalyzed, consecutive double C?H oxidative coupling of free 1-naphthylamine and α,β-unsaturated esters through C?H/C?H and C?H/N?H bonds is reported. The one step reaction leads to the formation of biologically important alkylidene-1,2-dihydrobenzo[cd]indoles scaffolds. This efficient process is much more synthetically convenient and useful than others because the starting materials, such as 1-naphthylamine derivatives are readily available and the free amine serves as a directing group.
Y06014 is a selective BET inhibitor for the treatment of prostate cancer
Wu, Tian-bang,Xiang, Qiu-ping,Wang, Chao,Wu, Chun,Zhang, Cheng,Zhang, Mao-feng,Liu, Zhao-xuan,Zhang, Yan,Xiao, Lin-jiu,Xu, Yong
, p. 2120 - 2131 (2021)
Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure?activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.
Discovery of Benzo[cd]indol-2(1H)-ones as Potent and Specific BET Bromodomain Inhibitors: Structure-Based Virtual Screening, Optimization, and Biological Evaluation
Xue, Xiaoqian,Zhang, Yan,Liu, Zhaoxuan,Song, Ming,Xing, Yanli,Xiang, Qiuping,Wang, Zhen,Tu, Zhengchao,Zhou, Yulai,Ding, Ke,Xu, Yong
, p. 1565 - 1579 (2016)
The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one containing compounds as a new class of BET bromodomain inhibitors, starting from structure-based virtual screening (SBVS). Through structure-based optimization, potent compounds were obtained with significantly improved activity. The two most potent compounds bind to the BRD4 bromodomain, with Kd values of 124 and 137 nM. Selected compounds exhibited high selectivity over other non-BET subfamily members. Notably, compound 85 demonstrated a reasonable antiproliferation effect on MV4;11 leukemia cells and exhibited a good pharmacokinetic profile with high oral bioavailability (75.8%) and moderate half-life (T1/2 = 3.95 h). The resulting lead molecule 85 represents a new, potent, and selective class of BET bromodomain inhibitors for the development of therapeutics to treat cancer and inflammatory diseases.
Silver-catalyzed stereoselective cyclization to polysubstituted (z)-1,2-dihydrobenzo [cd] indoles
Wang, Qiqi,Zhang, Lianpeng,Yao, Jinzhong,Qiu, Guanyinsheng,Li, Xiaofang,Zhou, Hongwei
, p. 4092 - 4098 (2018)
Silver-catalyzed stereoselective synthesis of polysubstituted (Z)-1,2-dihydrobenzo[cd]indoles from 8-ethynylnaphthalen-1-amines is reported. In this protocol, a series of nitrogen-containing heterocyclic compounds were synthesized by silver-catalyzed α-ad
Preparation method of aristolochia debilis alkaloid and intermediate thereof
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Paragraph 0057-0061, (2021/01/29)
The invention discloses a preparation method of aristolochia debilis alkaloid and an intermediate thereof; the preparation method of the intermediate comprises the step: under the action of a palladium catalyst and an additive, carrying out alkylation reaction on N-aryl-quinoline-2-formamide and alpha-bromoaryl ketone to obtain the intermediate of aristolochia debilis alkaloid. By adopting the preparation method of the intermediate as a key step, aristolochia debilis alkaloid with various functional groups can be synthesized, and the preparation method has important application significance indrug synthesis.
Aerobic Dehydrogenation of N-Heterocycles with Grubbs Catalyst: Its Application to Assisted-Tandem Catalysis to Construct N-Containing Fused Heteroarenes
Kawauchi, Daichi,Noda, Kenta,Komatsu, Yoshiyuki,Yoshida, Kei,Ueda, Hirofumi,Tokuyama, Hidetoshi
supporting information, p. 15793 - 15798 (2020/10/12)
An aerobic dehydrogenation of nitrogen-containing heterocycles catalyzed by Grubbs catalyst is developed. The reaction is applicable to various nitrogen-containing heterocycles. The exceptionally high functional group compatibility of this method was confirmed by the oxidation of an unprotected dihydroindolactam V to indolactam V. Furthermore, by taking advantage of the oxygen-mediated structural change of the Grubbs catalyst, we integrated ring-closing metathesis and subsequent aerobic dehydrogenation to develop the novel assisted-tandem catalysis using molecular oxygen as a chemical trigger. The utility of the assisted-tandem catalysis was demonstrated by the concise synthesis of N-containing fused heteroarenes including a natural antibiotic, pyocyanine.
Cobalt-Catalyzed Direct Carbonylative Synthesis of Free (NH)-Benzo[ cd]indol-2(1 H)-ones from Naphthylamides
Ying, Jun,Fu, Lu-Yang,Zhong, Guoqiang,Wu, Xiao-Feng
, p. 5694 - 5698 (2019/07/08)
A cobalt-catalyzed C-H carbonylation of naphthylamides for the synthesis of benzo[cd]indol-2(1H)-one scaffolds has been developed. The reaction employs a traceless directing group and uses benzene-1,3,5-triyl triormate as the CO source, affording various free (NH)-benzo[cd]indol-2(1H)-ones in moderate to high yields (up to 88%). Using this protocol, the total synthesis of BET bromodomain inhibitors A and B was accomplished as well.
