- Catalytic asymmetric addition of dialkylzinc to 3,4-dihydroisoquinoline N-oxides utilizing tartaric acid ester as a chiral auxiliary
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The catalytic asymmetric addition of dialkylzinc to a carbon-nitrogen double bond in 3,4-dihydroisoquinoline N-oxides was achieved by utilizing a catalytic amount of 2-magnesium 3-zinc salt of dicyclopentyl (R,R)-tartrate to afford (S)-1-alkyl-2-hydroxy-1
- Ukaji, Yutaka,Shimizu, Yuuko,Kenmoku, Yuuichi,Ahmed, Alauddin,Inomata, Katsuhiko
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Read Online
- Cobalt-catalyzed C[sbnd]H activation/C[sbnd]O formation: Synthesis of benzofuranones
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Herein, C[sbnd]H activation/C[sbnd]O formation reaction using novel cobalt catalytic system is reported. This reaction was given benzofuranones in moderate to excellent yields at room-temperature under air reaction conditions. The introduced strategy is efficient and low-cost method to synthesized benzofuranones from α,α-disubstitution acetic acid.
- Hajipour, Abdol R.,Khorsandi, Zahra
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- Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design
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Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of β-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor 1, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.
- Hoang, Van-Hai,Ngo, Van T.H.,Cui, Minghua,Manh, Nguyen Van,Tran, Phuong-Thao,Ann, Jihyae,Ha, Hee-Jin,Kim, Hee,Choi, Kwanghyun,Kim, Young-Ho,Chang, Hyerim,MacAlino, Stephani Joy Y.,Lee, Jiyoun,Choi, Sun
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p. 8011 - 8027
(2019/10/11)
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- Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase
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Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.
- Bennett, Matthew R.,Thompson, Mark L.,Shepherd, Sarah A.,Dunstan, Mark S.,Herbert, Abigail J.,Smith, Duncan R. M.,Cronin, Victoria A.,Menon, Binuraj R. K.,Levy, Colin,Micklefield, Jason
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supporting information
p. 10600 - 10604
(2018/08/17)
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- A tandem annulation with a [1,3]-hydride transfer as the key step leading to isochromans
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An unprecedented method that enables the direct coupling of an α-C-H bond in alcohols with 2-arylacetaldehydes through a [1,3]-hydride transfer ([1,3]-HT) of oxocarbenium ions catalyzed by a Lewis acid has been developed. The redox neutral preparation of
- Wang, Yingwei,Li, Guangxun,Liu, Hongxin,Tang, Zhuo,Cao, Yuan,Zhao, Gang
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supporting information
p. 10652 - 10655
(2017/10/06)
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- Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist
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TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5
- Agarwal, Sameer,Patil, Amit,Aware, Umesh,Deshmukh, Prashant,Darji, Brijesh,Sasane, Santosh,Sairam, Kalapatapu V. V. M.,Priyadarsiny, Priyanka,Giri, Poonam,Patel, Harilal,Giri, Suresh,Jain, Mukul,Desai, Ranjit C.
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supporting information
p. 51 - 55
(2016/02/03)
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- Tetrahydroberberine derivative and application thereof
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The invention relates to a tetrahydroberberine derivative and application thereof and relates to a compound represented by a formula (V) shown in the description, a preparation method therefor and application of the compound in medicine. Particularly, the invention relates to a derivative of the compound represented by the general formula (V), a preparation method for the derivative of the compound and use of the derivative of the compound in the prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, fatty degeneration of liver, type II diabetes, hyperglycemia, obesity or insulin resistance syndrome and metabolic syndrome. The compound disclosed by the invention can also be used for lowering total cholesterol, LDL (Low-Density Lipoprotein)-cholesterol and triglyceride, improving liver LDL receptor expression and inhibiting PCSK9 expression.
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Paragraph 0345; 0346
(2016/10/08)
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- Tetrahydrocoptisine derivative and applications thereof
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The present invention relates to a compound as shown in a formula (VII), a preparation method and applications thereof in medicines. In particular, the present invention relates to a derivative of the compound as shown in the formula (VII), a preparation method, and the applications of the derivative used as a therapeutic agent in prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, II-type diabetes, hyperglycemia, obesity or insulin resistance syndrome and metabolic syndrome. The compound disclosed by the present invention can also reduce total cholesterol, LDL-cholesterol and triglyceride, and increases expression of a liver LDL receptor and decreases expression of PCSK9.
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Paragraph 0301; 0302
(2016/10/08)
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- 2-THIO-IMIDAZOLE DERIVATIVES AS TGR5 MODULATORS
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The present invention relates to compounds of the general Formula I their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, their N-oxide, metabolites, polymorphs, use of these compounds in medicine for treating diabetes (TGR5 modulators) and the intermediates involved in their preparation.
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Page/Page column 62
(2013/04/25)
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- TRIAZOLE AND IMIDAZOLE DERIVATIVES FOR USE AS TGR5 AGONISTS IN THE TREATMENT OF DIABETES AND OBESITY
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The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprise
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Page/Page column 133
(2012/01/30)
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- NOVEL ISOQUINOLINE DERIVATIVES OR SALTS THEREOF
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The compound of the present invention relates to a drug, particularly to a novel isoquinoline derivative or its salt having an If current inhibitory effect without serious side effects such as convulsion and also to a drug, particularly a cardiac rate lowering agent, containing the compound as the active ingredient. Namely, the compound has a current If inhibitory effect and is particularly useful as a cardiac rate lowering agent for preventing ischemic heart diseases such as angina and cardiac infarction and circulatory diseases such as congestive cardiac insufficiency and arrhythmia (supraventricular arrhythmia). The present invention relates to dialkoxy-1,2,3,4-tetrahydroquinoline-2-carbonylpiperidino-3,4-dialkoxypropaneanilide derivatives, etc.
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- Catalytic turnover of benzylamine by a model for the lysine tyrosylquinone (LTQ) cofactor of lysyl oxidase
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Lysyl oxidase differs from other copper amine oxidases in that its active quinone cofactor reflects cross-linking of a lysyl residue into the tyrosine-derived quinone nucleus found in the plasma and other copper amine oxidases. A model for the lysyl oxida
- Ling,Kim,Sayre
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p. 9606 - 9611
(2007/10/03)
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- Process for preparing benzylnitriles
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A process is described for preparing an aromatic compound substituted by a tertiary nitrile of Formula (1.0.0): comprising treating a substituted aromatic compound of Formula (2.0.0): with a secondary nitrile of Formula (3.0.0): in the presence of a base having a pKanumerical value in the range of from about 17 to about 30, provided that the difference in pKanumerical values between said base and the corresponding tertiary nitrile of Formula (3.0.0) is no more than about 6; in an aprotic solvent having a dielectric constant (∈) of less than about 20; and at a reaction temperature in the range of from about 0° C. to about 120° C.; whereby there is formed said tertiary-nitrile-substituted aromatic compound final product of Formula (1.0.0); wherein the constituent parts W1, W2, W3, W4, and W5; and the substituent moieties R1, R2, R3, R4, R5, R6, and R7in the compounds of Formulas (1.0.0), (2.0.0) and (3.0.0) are selected from known organic groups and radicals as further detailed in the instant specification.
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