5551-72-4Relevant academic research and scientific papers
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 (2021/03/15)
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.
2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof
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Paragraph 0172; 0173, (2018/02/28)
The present invention relates to the technical field of medicinal chemistry, and in particular discloses a 2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof. The compound and pharmaceutically acceptable salt, isomer, racemate, prodrug, co-crystallized complex, hydrate, and solvate thereof can effectively inhibit the BET bromodomain receptor, and can be used for preparing a medicine for treating cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections.
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 (2016/03/05)
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.
Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation
Zhang, Yan,Xue, Xiaoqian,Jin, Xiangyu,Song, Yu,Li, Jing,Luo, Xiaoyu,Song, Ming,Yan, Weiqun,Song, Hongrui,Xu, Yong
, p. 431 - 441 (2014/04/17)
Retinoic acid receptor-related orphan receptor γ (RORγ), a member of the nuclear hormone receptor superfamily, is a promising therapeutic target for treating Th17-mediated autoimmune diseases. We performed structure-based virtual screening targeting the RORγ ligand-binding domain. Among the tested compounds, s4 demonstrated RORγ antagonistic activities with micromolar IC50 values in both an AlphaScreen assay (20.27 μM) and a cell-based reporter gene assay (11.84 μM). Optimization of the s4 compound led to the identification of compounds 7j, 8c, 8k, and 8p, all of which displayed significantly enhanced RORγ inhibition with IC 50 values of 40-140 nM. These results represent a promising starting point for developing potent small molecule RORγ inhibitors.
OPTICAL FILTER
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Page/Page column 22; 26, (2011/07/06)
An optical filter containing at least one naphtholactam derivative represented by general formula (I), wherein X is oxygen or sulfur; R1, R2, R3, R4, R5, R6, and Y are each hydrogen, halogen, nitro, cyano, aldehyde, carboxyl, hydroxyl, —NRR′, organosilyl, optionally substituted C1-C30 alkyl, optionally substituted C6-C30 aryl, or optionally substituted C7-C30 arylalkyl; and R and R′ are each hydrogen, optionally substituted C1-C30 alkyl, or optionally substituted C6-C30 aryl.
Studies on the Lossen-type rearrangement of N-(3-phenylpropionyloxy) phthalimide and N-tosyloxy derivatives with several nucleophiles
Chanmiya Sheikh,Takagi, Shunsuke,Ogasawara, Asako,Ohira, Masayuki,Miyatake, Ryuta,Abe, Hitoshi,Yoshimura, Toshiaki,Morita, Hiroyuki
supporting information; experimental part, p. 2132 - 2140 (2010/04/26)
The reaction of N-(3-phenylpropionyloxy)phthalimide (1a) and N-tosyloxy (5a,b) derivatives with nucleophiles was examined and found to give the products via Lossen-type rearrangement. In order to obtain the scope of this reaction mechanism, further studies the reaction of several N-sulfonyloxyimide derivatives with various nucleophiles under similar conditions were carried out and found to afford the corresponding same types of products in high yields.
Photocleavage of o-nitrobenzyl ether derivatives for rapid biomedical release applications
Kim, Moon Suk,Diamond, Scott L.
, p. 4007 - 4010 (2007/10/03)
The externally controlled cleavage of covalently linked prodrugs, proteins, or solid-phase formulation vehicles offers potential advantages for controlled drug or gene delivery. A series of o-nitrobenzyl ester compounds (1-8) were synthesized to allow a systematic study of photolability. The o-nitrobenzyl ester was strictly required for photolability, while imido esters were not photolabile. The degradation kinetics of 1-o-phenylethyl ester was an order of magnitude faster than that of o-nitrobenzyl ester. Tosylate, phosphate, and benzoate derivatives of 1-o-nitrophenylethyl displayed similar photolability (>80% decomposition within 10 min at 3.5 mW/cm2 at 365 nm). O-o-Nitrobenzyl O′,O″-diethyl phosphate displayed the fastest decomposition at photoirradiation condition (3.5 mW/cm2, 365 nm) suitable for biological systems. We report the synthesis and photo-decomposition of 1-o-nitrophenylethyl derivatives amenable for the creation of photolabile prodrugs or formulation particles for drug depots, DNA condensation, or tissue engineering applications.
