79477-87-5Relevant academic research and scientific papers
Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95
Zang, Jie,Ye, Fei,Solbak, Sara M. ?.,H?j, Lars J.,Zhang, Mingjie,Bach, Anders
supporting information, p. 949 - 954 (2020/12/31)
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.
General Synthesis of Chiral α,α-Diaryl Carboxamides by Enantioselective Palladium-Catalyzed Cross-Coupling
Li, Bowen,Aliyu, Muinat A.,Gao, Zhenhua,Li, Tiejun,Dong, Wei,Li, Junchen,Shi, Enxue,Tang, Wenjun
, p. 4974 - 4978 (2020/07/03)
A general synthesis of chiral α,α-diaryl carboxamides is developed by enantioselective cross-coupling between 2-bromo-2-aryl carboxamides and arylboronic acids, leading to a series of chiral α,α-diaryl carboxamides with various electronic properties and functionalities in moderate to excellent enantioselectivities and yields. The employment of a sterically bulky chiral P,P═O ligand L2 is critical for the reactivity and selectivity. This protocol is applied to an efficient asymmetric synthesis of a key intermediate of dopamine receptor agonist SKF 38393.
Novel synthesis method of benzene ring polysubstituted compound based on benzoyl formic acid
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Paragraph 0027-0033; 0062-0068, (2020/05/30)
The invention relates to a novel synthesis method of a benzene ring polysubstituted compound based on benzoyl formic acid. According to the synthesis method, an acetophenone-based benzene ring polysubstituted compound is used as a raw material, a specific
Reductive carboxylation of aromatic esters by electron transfer from magnesium metal
Maekawa, Hirofumi,Okawara, Hikaru,Murakami, Taro
supporting information, p. 206 - 209 (2016/12/28)
Magnesium-promoted reductive carboxylation of ethyl benzoate in the presence of chlorotrimethylsilane in N,N-dimethylformamide brought about a new carbon-carbon bond formation between the carbonyl carbon atom and carbon dioxide to give the corresponding benzoylformic acid in good yield. It is noteworthy that only ethyl benzoates with substituents at the meta-position were converted into benzoylformic acid derivatives. Moreover, no mandelic acid was detected even under the reductive conditions. This result indicates that benzoylformic acid was obtained after hydrolysis of a carboxylated intermediate, which would be alive as a stabilized structure in the reaction media.
Enzymatic Resolution by a d-Lactate Oxidase Catalyzed Reaction for (S)-2-Hydroxycarboxylic Acids
Sheng, Binbin,Xu, Jing,Ge, Yongsheng,Zhang, Shuo,Wang, Danqi,Gao, Chao,Ma, Cuiqing,Xu, Ping
, p. 2630 - 2633 (2016/08/30)
Oxidase-catalyzed kinetic resolution is important for the production of enantiopure 2-hydroxycarboxylic acids (2-HAs), which are versatile building blocks for the synthesis of many significant compounds. However, in contrast to that of (R)-2-HAs, the production of (S)-2-HA is challenging because of the lack of related oxidases. Herein, suitable enzymes were screened systematically through the analysis of numerous putative d-lactate oxidase sequences and identification of several required properties. Finally, a d-lactate oxidase from Gluconobacter oxydans 621H with advantageous characteristics, such as good solubility, broad substrate spectrum, and high stereoselectivity, was selected to resolve 2-HAs into (S)-2-HAs. A variety of (S)-2-HAs was produced successfully using this d-lactate oxidase with excellent enantiomeric excess values (>99 %). The presented screening criteria and approach for target biocatalysis suggested a guideline for the production of optically active chemicals such as (S)-2-HAs.
Asymmetric friedel-crafts alkylation of α-substituted β-nitroacrylates: Access to β2,2-amino acids bearing indolic all-carbon quaternary stereocenters
Weng, Jian-Quan,Deng, Qiao-Man,Wu, Liang,Xu, Kai,Wu, Hao,Liu, Ren-Rong,Gao, Jian-Rong,Jia, Yi-Xia
supporting information, p. 776 - 779 (2014/03/21)
A highly enantioselective Friedel-Crafts alkylation reaction of indoles with acyclic α-substituted β-nitroacrylates is developed under the catalysis of Ni(ClO4)2-bisoxazoline complex at 1 mol % catalyst loading, affording chiral indolic β-nitroesters bearing all-carbon quaternary stereocenters in excellent yields and ees of up to 97%. Transformation of one of the products to β2,2-amino ester and tetrahydro-β-carboline through nitro reduction and sequential Pictet-Spengler cyclization was exemplified.
Enantio- and chemoselective Br?nsted-acid/Mg(nBu) 2 catalysed reduction of α-keto esters with catecholborane
Enders, Dieter,St?ckel, Bianca A.,Rembiak, Andreas
supporting information, p. 4489 - 4491 (2014/04/17)
The first enantio- and chemoselective Br?nsted-acid catalysed reduction of α-keto esters with catecholborane has been developed. The α-hydroxy esters were obtained under mild reaction conditions in virtually quantitative yields and excellent enantioselectivities. With slight modifications both enantiomers can be obtained without any loss of selectivity. This journal is the Partner Organisations 2014.
1, 2, 4-TRIAZOLONE DERIVATIVE
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Paragraph 0248; 0249; 0254, (2013/08/14)
The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.
Reduction of manganate(VI) by mandelic acid and its significance to development of a general mechanism for oxidation of organic compounds by high-valent transition metal oxides
Lee, Donald G.,Chen, Tao
, p. 11231 - 11236 (2007/10/02)
Results obtained from a study of the oxidation of mandelic acid and cyclobutanol by manganate(VI) indicate that reaction mechanisms traditionally applied to oxidations of this type (i.e., hydrogen atom or hydride ion transfers) may not be correct. Instead it appears that the reaction may be initiated by a 2 + 2 addition of the α-C-H bond to a manganese oxo double bond. This interpretation may be useful in the development of a general mechanism for the oxidation of organic compounds by high-valent transition metal oxides including more common oxidants such as permanganate, ruthenium tetroxide, and chromic acid.
The Oxidation of Alcohols by Permanganate. A Comparison with Other High-Valent Transition-Metal Oxidants
Lee, Donald G.,Chen, Tao
, p. 5341 - 5345 (2007/10/02)
The results obtained from a study of the oxidation of mandelic acid and cyclobutanol by permanganate in 1.0 M KOH are best accomodated by a mechanism in which the initial reaction is the addition of a manganese-oxo bond to the α-C-H bond of the alcohol, followed by homolytic cleavage of the resulting Mn-C bond to give free-radical intermediates.A comparison with other high-valent transition-metal oxidants suggests that it is possible to systematically classify the way in which these reagents react with alcohols on the basis of the initial reaction (C-H or O-H addition) and the cleavage mode of the metal-oxygen or metal-carbon bond (homolytic or heterolytic).The approach provides a framework for understanding these reactions that is less chaotic than the current situation where distinctive mechanisms have been proposed for each individual oxidant.
