1481-27-2Relevant articles and documents
Discovery of novel 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole analogs as promising very long chain fatty acids inhibitors
Lin, Jian,Li, Yitao,Hu, Xiaoyun,Chi, Weilin,Zeng, Shuiming,Xu, Junxing
, p. 226 - 240 (2020/10/19)
Very long chain fatty acids (VLCFAs) are one of the most principal and promising targets for herbicides discovery. In order to explore and find novel VLCFAs inhibitors with higher herbicidal activity and improved crop safety, a variety of new 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole derivatives were reasonably designed and synthesized. The results of greenhouse experiments indicated that several compounds exhibited good herbicidal activity against Digitaria sanguinalis, Echinochloa crus-galli, and Setaria faberii at rates of 150 g ai/ha. Compounds g4 and h1 displayed promising herbicidal activity against D sanguinalis and E crus-galli at rates of 75 g ai/ha, which is better than commercial pyroxasulfone and S-metolachlor. Moreover, compound h1 displayed higher activity against E crus-galli, D sanguinalis, and S faberii than pyroxasulfone and S-metolachlor even at a rate of 37.5 and 18.75 g ai/ha. Furthermore, both of the compounds g4 and h1 were much safer to these tested crops, especially to rice, wheat and rape, at the rate of 150 g ai/ha than pyroxasulfone. Therefore, h1 may act as a new lead structure for novel herbicides discovery.
SALTS AND SOLID FORMS AND PROCESSES OF PREPARING A PI3K INHIBITOR
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Page/Page column 67; 68, (2021/08/13)
The present disclosure provides processes for preparing (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, which is useful as an inhibitor phosphoinositide 3-kinase-delta (PI3Kδ), a
Optimized TrkB Agonist Ameliorates Alzheimer's Disease Pathologies and Improves Cognitive Functions via Inhibiting Delta-Secretase
Chen, Chun,Ahn, Eun H.,Liu, Xia,Wang, Zhi-Hao,Luo, Shilin,Liao, Jianming,Ye, Keqiang
, p. 2448 - 2461 (2021/06/30)
BDNF/TrkB neurotropic pathway, essential for neural synaptic plasticity and survival, is deficient in neurodegenerative diseases including Alzheimer's disease (AD). Our previous works support that BDNF diminishes AD pathologies by inhibiting delta-secreta
HETEROCYCLIC FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO
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, (2020/03/02)
In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of
ISOXAZOLINE DERIVATIVES AND THEIR USES IN AGRICULTURE RELATED APPLICATION
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Paragraph 00208, (2019/04/26)
The present invention provides isoxazoline derivatives and uses thereof in agriculture; in particular, the present invention provides a compound having formula (I), or a stereoisomer, an N-oxide or a salt thereof, preparation methods thereof, and compositions containing these compounds and uses thereof in agriculture, particularly uses as herbicide active ingredients for controlling unwanted plants; wherein R1, R2, R3, R4, n, R5, R6 and Hy are as described in the invention.
A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib
Du, Fangyu,Zhou, Qifan,Shi, Yajie,Yu, Miao,Sun, Wenjiao,Chen, Guoliang
, p. 576 - 586 (2019/02/01)
A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.
5-6-5 azatricyclic compound and preparation method thereof
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, (2019/10/01)
The embodiment of the invention discloses a preparation method of a 5-6-5 azatricyclic compound. By using 3-fluorophenol as a raw material and through multistep cascade reactions including esterification, rearrangement, oximation, intramolecular cyclizati
Structure-Based Discovery and Optimization of Benzo [d] isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC)
Zhang, Maofeng,Zhang, Yan,Song, Ming,Xue, Xiaoqian,Wang, Junjian,Wang, Chao,Zhang, Cheng,Li, Chenchang,Xiang, Qiuping,Zou, Lingjiao,Wu, Xishan,Wu, Chun,Dong, Baijun,Xue, Wei,Zhou, Yulai,Chen, Hongwu,Wu, Donghai,Ding, Ke,Xu, Yong
, p. 3037 - 3058 (2018/04/23)
The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.
A kind of benzo [d] different wicked zuozuo apperception compound and use thereof
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, (2018/06/14)
The invention relates to the technical field of chemical medicine, and particularly discloses a benzo[d]isoxazole compound shown as a general formula (A) and application thereof. The compound can effectively inhibit bromodomain of BET family proteins so as to block interaction between the BET family proteins and chromatin histone to adjust genetic transcription, cause changing of a downstream signal path and exert important influence on various diseases, so that the compound and a combination thereof can be used for preparing medicine for treating or preventing diseases like tumorigenesis, inflammation, viral infection, cell proliferation disorder, autoimmune diseases and septicemia.
Discovery of small-molecule inhibitors selectively targeting the DNA-binding domain of the human androgen receptor
Li, Huifang,Ban, Fuqiang,Dalal, Kush,Leblanc, Eric,Frewin, Kate,Ma, Dennis,Adomat, Hans,Rennie, Paul S.,Cherkasov, Artem
supporting information, p. 6458 - 6467 (2014/10/15)
The human androgen receptor (AR) is considered as a master regulator in the development and progression of prostate cancer (PCa). As resistance to clinically used anti-AR drugs remains a major challenge for the treatment of advanced PCa, there is a pressing need for new anti-AR therapeutic avenues. In this study, we identified a binding site on the DNA binding domain (DBD) of the receptor and utilized virtual screening to discover a set of micromolar hits for the target. Through further exploration of the most potent hit (1), a structural analogue (6) was identified demonstrating 10-fold improved anti-AR potency. Further optimization resulted in a more potent synthetic analogue (25) with anti-AR potency comparable to a newly FDA-approved drug Enzalutamide. Site-directed mutagenesis demonstrated that the developed inhibitors do interact with the intended target site. Importantly, the AR DBD inhibitors could effectively inhibit the growth of Enzalutamide-resistant cells as well as block the transcriptional activity of constitutively active AR splice variants, such as V7.
