16859-59-9Relevant articles and documents
Kinetics of the equilibration of 3-hydroxyphtalide and o-formylbenzoic acid. Hemiacetal breakdown with a carboxylic acid leaving group
McClelland, Robert A.,Soerensen, Poul E.
, p. 1196 - 1200 (1986)
A temperature-jump relaxation study is reported for the equilibration: 3-hydroxyphtalide (SH) o-formylbenzoate (R-) o-formylbenzoic acid (RH).A kinetic analysis is carried out in which SH and R- interconvert with catalysis in the ring opening direction by water and by added general bases.Excellent Broensted plots based upon a series of oxyacid buffer catalysts are obtained.These have slopes β for the base-catalyzed ring opening of 0.81 and α for the reverse acid-catalyzed ring closing of 0.19.A mechanism where S-, the conjugate base of SH, is a discrete intermediate can be ruled out on the basis of the Broensted values and the magnitudes of the rate constants.The lifetime of S- is estimated to lie in the range 1E-11-1E-15 s.Two mechanisms can be proposed.A fully concerted mechanism "enforced" by lifetimes less than 1E-13 s involves direct interconversion of SH and R- with no intermediate.A preassociated mechanism "enforced" by lifetimes in the 1E-11-1E-12 s range requires, in the ring closing direction, that an acid catalyst be hydrogen bonded to the carbonyl in R-.
Development of 5-hydroxyl-1-azabenzanthrone derivatives as dual binding site and selective acetylcholinesterase inhibitors
Chen, Li,Lei, Zhichao,Sun, Jianbo,Sun, Xiaona,Wang, Yujin,Yue, Shasha
, (2022/03/27)
A series of novel 5-hydroxyl-1-azabenzanthrone derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (AD). The most effective Compound 16 showed selective inhibition of acetylcholinesterase (eeAChE IC50 = 0.045 μM; eeBuChE IC50 = 19.68 μM; SI = 437.33). Most of the compounds showed cytoprotective effects on PC12 cells damaged by hydrogen peroxide, which might be related to their antioxidant activity. Further experiments confirmed that 16 exhibited anti-apoptotic effects at low concentrations and reduced the relative level of ROS generation in PC12 cells. The expression level of proteins related to antioxidant stress pathway in PC12 cells was relatively increased after administrated with 16, which may be beneficial to delay the progression of the disease. Moreover, 16 was evaluated to be safe in vivo and in vitro, and showed good overall pharmacokinetic performance and high bioavailability (Foral = 55.5%). Besides, 16 showed comparable performance in ameliorating the scopolamine-induced cognition impairment to donepezil. In addition, in vitro BBB permeability experiments confirmed that 16 had high BBB permeability.
Chiral Bicyclic Imidazole-Catalyzed Acylative Dynamic Kinetic Resolution for the Synthesis of Chiral Phthalidyl Esters
Zhou, Muxing,Gridneva, Tatiana,Zhang, Zhenfeng,He, Ende,Liu, Yangang,Zhang, Wanbin
, p. 1641 - 1645 (2020/11/30)
Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, an alternative route has been developed for the efficient synthesis of chiral phthalidyl ester prodrugs via dynamic kinetic resolution of 3-hydroxyphthalides through enantioselective acylation (up to 99 % ee). The computational studies suggest a general base catalytic mechanism differing from the widely accepted nucleophilic catalytic mechanism. The structure analysis of the key transition states shows that the CH-π interactions and not the previously considered cation/π-π interactions between the catalyst and substrate is the dominant factor giving rise to the observed stereocontrol.
Oxoisoaporphine alkaloid derivative as well as preparation method and application thereof
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Paragraph 0034-0037, (2021/08/19)
The invention belongs to the field of biological medicine, and discloses an oxoisoaporphine alkaloid derivative shown in a formula II, X is O, R is selected from H and heterocyclic radical containing one or more N, and n is an integer ranging from 2 to 4. Pharmacological experiment research shows that the oxoisoaporphine alkaloid derivative disclosed by the invention has excellent acetylcholin esterase and A beta inhibitory activity, and the invention also discloses an application of the oxoisoaporphine alkaloid derivative in preparation of an anti-Alzheimer disease drug.
Industrial synthesis method of o-aldehyde phenyl fatty acid
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Paragraph 0074; 0076; 0077; 0083; 0085; 0086; 0088; 0090, (2020/01/08)
The invention provides an industrial synthesis method of o-aldehyde phenyl fatty acid, which comprises the following steps: by using aromatic lactone or o-methylphenyl fatty acid as a raw material, carrying out halogenation reaction and hydrolysis to obtain the o-aldehyde phenyl fatty acid. In the method, halogen is used in the production process; however, if haloid acid or haloid salt formed byhydrolysis is directly discharged to the environment, the cost of a halogen source accounts for most of the cost of the whole process, and severe environmental pollution is caused; by means of the method, an activated halogen source can be obtained in real time by adding a specific oxidant in the reaction process, so that the closed cycle of halogen elements is realized by means of the subsequenthydrolysis process; therefore, a large amount of raw material cost is saved on the whole, environmental pollution is reduced, the product yield is high, and large-scale production is facilitated.
DL-3-n-butylphthalide-Edaravone hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer's therapy
Qiang, Xiaoming,Li, Yan,Yang, Xia,Luo, Li,Xu, Rui,Zheng, Yunxiaozhu,Cao, Zhongcheng,Tan, Zhenghuai,Deng, Yong
, p. 718 - 722 (2017/02/10)
Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, compounds 9a–d exhibited good inhibition of self-induced Aβ1-42aggregation with inhibition ratio 57.7–71.5%. For MAO, these new hybrids exhibited good balance of inhibition for MAO-A and MAO-B. In addition, all target compounds retained the antioxidant activity of edaravone, showed equal or better antioxidant activity than edaravone. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compounds 9a–d would be able to cross the blood-brain barrier and reach their biological targets in the central nervous system. The promising results in all assays demonstrated that the strategy behind the designing of compounds was rational and favourable. Taken together, these preliminary findings suggested that the compounds with the strongest bioactivity deserves further investigated for pharmacological development in AD therapy.
ENEDIYNE COMPOUNDS, CONJUGATES THEREOF, AND USES AND METHODS THEREFOR
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Page/Page column, (2013/08/28)
Enediyne compounds having a structure according to formula (I), where R0, R2, R3, R4, R5, R6, and R7 are defined herein, can be used in chemotherapeutic drugs, especially in conjugates, for the treatment of diseases such as cancer.
Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin- 5(9bH)-ones as 5-HT2C receptor agonists
Fevig, John M.,Feng, Jianxin,Rossi, Karen A.,Miller, Keith J.,Wu, Ginger,Hung, Chen-Pin,Ung, Thao,Malmstrom, Sarah E.,Zhang, Ge,Keim, William J.,Cullen, Mary Jane,Rohrbach, Kenneth W.,Qu, Qinling,Gan, Jinping,Pelleymounter, Mary Ann,Robl, Jeffrey A.
, p. 330 - 335 (2013/02/25)
A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT2C agonism with excellent selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model.
Cyclopentadienylcobalt-mediated intermolecular cycloaddition of ,α ω-diynes to (Cyclo)alkenes: Synthesis of linearly fused fligocycles and extension to enantiomerically pure (6a R,10a R)-dihydroanthracyclinones
Aubert, Corinne,Gandon, Vincent,Han, Sangdon,Johnson, Barry M.,Malacria, Max,Schoemenauer, Sten,Vollhardt, K. Peter C.,Whitener, Glenn D.
experimental part, p. 2179 - 2200 (2010/09/06)
The generality of the [CpCoL2]-mediated [2+2+2] cycloaddition of , α ω-diynes to (cyclo)alkenes has been extended to include linear oligocycles as models for the one-step, A + D→ ABCD construction of optically pure, novel 6,10-dihydroanthracyclinones. Georg Thieme Verlag Stuttgart - New York.
Photo-oxidation of aldehydes with molecular oxygen in the presence of catalytic bromine or hydrobromic acid
Hirashima, Shin-Ichi,Itoh, Akichika
, p. 156 - 158 (2007/10/03)
Aldehydes were found to be oxidized with molecular oxygen to the corresponding carboxylic acid in the presence of catalytic hydrobromic acid or bromine under photo-irradiation.
