- Optimized TrkB Agonist Ameliorates Alzheimer's Disease Pathologies and Improves Cognitive Functions via Inhibiting Delta-Secretase
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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
- Chen, Chun,Ahn, Eun H.,Liu, Xia,Wang, Zhi-Hao,Luo, Shilin,Liao, Jianming,Ye, Keqiang
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p. 2448 - 2461
(2021/06/30)
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- 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
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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.
- Lin, Jian,Li, Yitao,Hu, Xiaoyun,Chi, Weilin,Zeng, Shuiming,Xu, Junxing
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p. 226 - 240
(2020/10/19)
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- SALTS AND SOLID FORMS AND PROCESSES OF PREPARING A PI3K INHIBITOR
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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
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Page/Page column 67; 68
(2021/08/13)
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- HETEROCYCLIC FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO
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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
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Page/Page column 30
(2020/03/02)
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- 5-6-5 azatricyclic compound and preparation method thereof
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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
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Paragraph 0033; 0037-0039
(2019/10/01)
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- ISOXAZOLINE DERIVATIVES AND THEIR USES IN AGRICULTURE RELATED APPLICATION
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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.
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Paragraph 00208
(2019/04/26)
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- A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib
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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.
- Du, Fangyu,Zhou, Qifan,Shi, Yajie,Yu, Miao,Sun, Wenjiao,Chen, Guoliang
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p. 576 - 586
(2019/02/01)
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- 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)
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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.
- 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
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p. 3037 - 3058
(2018/04/23)
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- A kind of benzo [d] different wicked zuozuo apperception compound and use thereof
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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.
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Paragraph 0331; 0333; 0337; 0338
(2018/06/14)
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- Discovery of small-molecule inhibitors selectively targeting the DNA-binding domain of the human androgen receptor
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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.
- Li, Huifang,Ban, Fuqiang,Dalal, Kush,Leblanc, Eric,Frewin, Kate,Ma, Dennis,Adomat, Hans,Rennie, Paul S.,Cherkasov, Artem
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supporting information
p. 6458 - 6467
(2014/10/15)
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- Broadening the catalyst and reaction scope of regio- and chemoselective C-H oxygenation: A convenient and scalable approach to 2-acylphenols by intriguing Rh(ii) and Ru(ii) catalysis
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A unique Rh(ii) and Ru(ii) catalyzed C-H oxygenation of aryl ketones and other arenes has been developed for the facile synthesis of diverse functionalized phenols. The reaction demonstrates excellent reactivity, regio- and chemoselectivity, good functional group compatibility and high yields. The practicality of this method has been proved by gram-scale synthesis of a few different 2-acylphenols. Its utility has been well exemplified in further applications in heterocycle synthesis and direct modifications of drug Fenofibrate.
- Shan, Gang,Han, Xuesong,Lin, Yun,Yu, Shanyou,Rao, Yu
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supporting information
p. 2318 - 2322
(2013/04/10)
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- Pd-catalyzed sp2 C-H hydroxylation with TFA/TFAA via weak coordinations
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An efficient sp2 C-H hydroxylation has been developed for the synthesis of a wide range of functionalized phenols with aryl ketones, benzoates, benzamides, acetanilides and sulfonamides through palladium(II) catalysis. A trifluoroacetic acid (TFA)/trifluoroacetic anhydride (TFAA) co-solvent system serves as the oxygen source and is the critical factor for weak coordination promoted C-H activation. Georg Thieme Verlag Stuttgart New York.
- Rao, Yu
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p. 2472 - 2476
(2013/12/04)
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- Pd-catalyzed C-H oxygenation with TFA/TFAA: Expedient access to oxygen-containing heterocycles and late-stage drug modification
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Functionalized phenols are valuable industrial chemicals related to pharmaceuticals, agrochemicals, and polymers. Therefore, the direct catalytic hydroxylation of arenes to produce phenols has attracted much attention. Although tremendous progress has been made in this field, there are still difficult substrates which remain unmet challenges for direct hydroxylation in terms of regio- and chemoselectivity, as well as the practicality of current methods (Scheme 1). For example, 2-hydroxy aromatic ketones are useful synthetic intermediates for the preparation of various oxygen-containing heterocycles such as benzofuranone, chromanone, benzoxazole, and dibenzooxazepine; they also serve as key building blocks for drugs such as celiprolol, acebutolol, and propafenone. Traditional strategies for accessing 2-hydroxy aromatic ketones have mainly involved the oxidation of benzylic alcohols, the hydrolysis of aromatic halides, Fries rearrangement of esters or the demethylation of methyl phenyl ether. These methods generally suffer from one limitation or another, such as tedious reaction procedures, harsh reaction conditions, low yields, or the formation of side products. Hence, direct transformation of readily available aromatic ketones into valuable 2-hydroxylated products by transition metal-catalyzed C-H functionalization is arguably a highly efficient and atom-economic method to access these compounds. Moreover, developing a more general strategy for the regio- and chemoselective C-H oxygenation of a variety of challenging arenes would be especially desirable for phenol synthesis (Scheme 1).
- Shan, Gang,Yang, Xinglin,Ma, Linlin,Rao, Yu
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supporting information
p. 13070 - 13074
(2013/02/26)
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- Direct acylation of phenol and naphthol derivatives in a mixture of graphite and methanesulfonic acid
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Graphite in methanesulfonic acid is used to prepare o-hydroxyketones by direct acylation of phenol and naphthol derivatives with carboxylic acids. Georg Thieme Verlag Stuttgart.
- Sharghi, Hashem,Hosseini-Sarvari, Mona,Eskandari, Razieh
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p. 2047 - 2052
(2007/10/03)
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- QSAR studies of paeonol analogues for inhibition of platelet aggregation
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Various paeonol analogues were synthesized and tested in vitro as inhibitors of platelet aggregation. Structural properties (or descriptors) of paeonol analogues were calculated and the structure-activity relationships were determined. Several multiple linear and nonlinear regression models and back-propagation neural network model were tested and the latter using relative positive charge, hydration energy, and hydrophilic factor as inputs gave the best data fitting with R2 = 0.89 and qpre2=0.66. The correlation coefficient between antiplatelet inhibition activity with an interaction energy between the paeonol compounds with COX-1 enzyme is only 0.39.
- Doble, Mukesh,Karthikeyan,Padmaswar,Akamanchi
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p. 5996 - 6001
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF 6-(PERFLUOROALKYL)URACIL COMPOUNDS FROM CARBAMATE COMPOUNDS
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An improved process for the preparation of 6-(perfluoroalkyl)uracil compounds having structural formula (I) from carbamate compounds having structural formula (II).
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- 7- (1, 3-THIAZOL-2-YL)THIO!-COUMARIN DERIVATIVES AND THEIR USE AS LEUKOTRIENE BIOSYNTHESIS INHIBITORS
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The instant invention provides compounds of Formula (I) which are leukotriene biosynthesis inhibitors. Compounds of formula (I) are useful as anti-asthmatic, anti-allergic, anti-inflammatory, cytoprotective and anti-artherosclerotic agents.
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- Processes and intermediate compounds for the preparation of 2-(N,N-disubstituted) amino-4-(perfluoroalkyl)-1, 3- oxazin-6-one and 6-(perfluoroalkyl) uracil compounds
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An improved process and intermediate compounds for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds having the structural formula I and an improved process for the preparation of 6-(perfluoroalkyl)uracil compound
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- Process for the preparation of 6-(perfluoroalkyl) uracil compounds form urea compounds
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An improved process for the preparation of 6-(perfluoroalkyl)uracil compounds having the structural formula I from urea compounds having the structural formula II
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- Process for the preparation of 6-(perfluoroalkyl) uracil compounds from 2-(N,N-disubstituted) amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds
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An improved process for the preparation of 6-(perfluoroalkyl)uracil compounds having the structural formula I from 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds having the structural formula II
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- Synthesis and in-vitro evaluation of platelet aggregation inhibitory activity of paeonol and its analogues
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Paeonol (1-(2-hydroxy-4-methoxyphenyl)ethanone) and a series of substituted 1-(2-hydroxyphenyl)ethanone derivatives were synthesized and screened as inhibitors of platelet aggregation. The compounds with the greatest anti-platelet potential among the series tested were 1-(2,5-dihydroxyphenyl)ethanone (65.36% inhibition at 300 μM against 5 μM ADP), paeonol(36.31%), 1-(2-hydroxy-5-methoxyphenyl)ethanone (24.47%), 1-(2-hydroxy-5-nitrophenyl) ethanone (30.40%) and 1-(5-chloro-2-hydroxy-4-methylphenyl)ethanone (24.43%).
- Akamanchi,Padmawar,Thatte,Rege,Dahanukar
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p. 323 - 329
(2007/10/03)
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- Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues
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The further development of allosteric HIV-1 RT inhibitors in the urea analogue series of PETT (phenylethylthiazolylthiourea) derivatives is described here. The series includes derivatives with an ethyl linker (1-5) and racemic (6-16) and enantiomeric (17-
- H?gberg, Marita,Sahlberg, Christer,Engelhardt, Per,Noréen, Rolf,Kangasmets?, Jussi,Johansson, Nils Gunnar,?berg, Bo,Vrang, Lotta,Zhang, Hong,Sahlberg, Britt-Louise,Unge, Torsten,L?vgren, Seved,Fridborg, Kerstin,B?ckbro, Kristina
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p. 4150 - 4160
(2007/10/03)
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- 3-(1,2-benzisothiazol- and isoxazol-5-Y1)-2,4(1H,3H)-pyrimidinedione or thione and 3-(1,2-benzisothiazol- and isoxazol-5-y1)-4(3H)-pyrimidinone or thione herbicidal agents
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There are provided 3-(1,2-benzisothiazol- and isoxazol-5-yl)-2,4(1H,3H)-pyrimidinedione or thione compounds of formula I and 3-(1,2-benzisothiazol- and isoxazol-5-yl)-4(3H)-pyrimidinone or thione compounds of formula II Further provided are compositions and methods comprising those compounds for the control of undesirable plant species.
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- Alumina in Methanesulfonic Acid (AMA) as a New Efficient Reagent for Direct Acylation of Phenol Derivatives and Fries Rearrangement. A Convenient Synthesis of o-Hydroxyarylketones
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Alumina in methanesulfonic acid (AMA) is used to prepare o-hydroxyaryl ketones by acylation of phenol and naphthol derivatives with carboxylic acids and the Fries rearrangement of phenolic esters. Mechanistic studies show that the acylation reaction in AMA occurred through an esterification followed by a Fries rearrangement of the phenolic ester by an intermolecular mechanism.
- Sharghi, Hashem,Kaboudin, Babak
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p. 2678 - 2695
(2007/10/03)
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- Imidazopyrimidines and Imidazopyrazines: The Role of Nitrogen Position in Inotropic Activity
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Congestive heart failure is a major medical problem for which existing medicaments have provided limited benefit.Recent new experimental drugs, including imidazo- and imidazopyridines, have both inotropic and vasodilatory properties.Subtle c
- Spitzer, Wayne A.,Victor, Frantz,Pollock, G. Don,Hayes, J. Scott
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p. 1590 - 1595
(2007/10/02)
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- Inotropic agents
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This invention provides for certain phenyl-substituted imidazo compounds, their pharmaceutical formulations, and their use as positive inotropic agents and vasodilators.
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