- Iron-catalyzed hydroaminocarbonylation of alkynes: Selective and efficient synthesis of primary α,β-unsaturated amides
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α,β-Unsaturated primary amides are important intermediates and building blocks in organic synthesis. Herein, we report a ligand-free iron-catalyzed hydroaminocarbonylation of alkynes using NH4HCO3 as the ammonia source, enabling the highly efficient and regioselective synthesis of linear α,β-unsaturated primary amides. Various aromatic and aliphatic alkynes are transformed into the desired linear α,β-unsaturated primary amides in good to excellent yields. Further studies show that using NH4HCO3 as the ammonia source is key to obtain good yields and selectivity. The utility of this route is demonstrated with the synthesis of linear α,β-unsaturated amides including vanilloid receptor-1 antagonist TRPV-1.
- Huang, Zijun,Jiang, Xiongwei,Lan, Donghui,Li, Yuehui,Pi, Shaofeng,Tan, Zhengde,Tang, Jia,Xie, Tianle,Yi, Bing,Zhang, Minmin
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supporting information
(2022/02/22)
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- (E)-4-methyl-2-(4-(trifluoromethyl) styryl) oxazole compound as well as preparation method and application thereof
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The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and in particular relates to an (E)-4-methyl-2-(4-(trifluoromethyl) styryl) oxazole compound as well as a preparation method and an application thereof. The structural general formula of the compound is shown in the specification, wherein an R1 group is substituted by a 2-position, 3-position or 4-position mono-substituted fluorine atom, methyl, chlorine atom, methoxy group, bromine atom or an unsubstituted group; and the R2 group is substituted by a 2-position, 3-position or 4-position mono-substituted methoxy group, a chlorine atom or an unsubstituted group. Pharmacological studies show that the compound has certain inhibitory activity on human non-small cell lung cancer A549 cells, can be used for preparing anti-tumor drugs, and opens up a new way for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.
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- A Facile Total Synthesis of Mubritinib
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A five-step, practical, and concise total synthesis of mubritinib is described. The synthesis utilized Friedel-Crafts acylation, click reaction, reduction, and demethylation for the construction of the triazole ring system as key steps. Another important feature of this synthesis is the Bredereck oxazole synthesis. The main advantages of this process are the improved yield and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of mubritinib.
- Wang, Rong,Cui, Menghan,Yang, Qing,Kuang, Chunxiang
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supporting information
p. 978 - 982
(2021/02/03)
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- Catalytic, transition-metal-free semireduction of propiolamide derivatives: Scope and mechanistic investigation
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We report a transition-metal-free trans-selective semireduction of alkynes with pinacolborane and catalytic potassium tert-butoxide. A variety of 3-substituted primary and secondary propiolamides, including an analog of FK866, a potent nicotinamide mononucleotide adenyltransferase (NMNAT) inhibitor, are reduced to the corresponding (E)-3-substituted acrylamide derivatives in up to 99% yield with >99:1 E/Z selectivity. Mechanistic studies suggest that an activated Lewis acid-base complex transfers a hydride to the α-carbon followed by rapid protonation in a trans fashion.
- Grams, R. Justin,Garcia, Christopher J.,Szwetkowski, Connor,Santos, Webster L.
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supporting information
p. 7013 - 7018
(2020/09/12)
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- Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex i
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Disruption of mitochondrial function selectively targets tumour cells that are dependent on oxidative phosphorylation. However, due to their high energy demands, cardiac cells are disproportionately targeted by mitochondrial toxins resulting in a loss of cardiac function. An analysis of the effects of mubritinib on cardiac cells showed that this drug did not inhibit HER2 as reported, but directly inhibits mitochondrial respiratory complex I, reducing cardiac-cell beat rate, with prolonged exposure resulting in cell death. We used a library of chemical variants of mubritinib and showed that modifying the 1H-1,2,3-triazole altered complex I inhibition, identifying the heterocyclic 1,3-nitrogen motif as the toxicophore. The same toxicophore is present in a second anti-cancer therapeutic carboxyamidotriazole (CAI) and we demonstrate that CAI also functions through complex I inhibition, mediated by the toxicophore. Complex I inhibition is directly linked to anti-cancer cell activity, with toxicophore modification ablating the desired effects of these compounds on cancer cell proliferation and apoptosis.
- Allen, Timothy E. H.,Chung, Injae,Fischer, Peter,Hardy, Rachel,Harvey, Robert F.,Hirst, Judy,Kellam, Barrie,Macfarlane, Marion,Mistry, Sarah,Pryde, Kenneth R.,Serreli, Riccardo,Stephenson, Zo? A.,Stoneley, Mark,Willis, Anne E.
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- Zinc-mediated facile synthesis of α,β-unsaturated primary amides
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A general method for the synthesis of α,β-unsaturated primary amides was achieved by an one-pot, triphenylphosphine-and zinc powder-promoted Wittig reaction of bromoacetamide and aldehydes under solvent-free conditions.
- Feng, Sunlin,Zhang, Zhiying,Jiang, Shilei,Yu, Xiaochun
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experimental part
p. 382 - 384
(2010/11/03)
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- Preventive/therapeutic method for cancer
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This invention provides a prophylactic or therapeutic method for cancer. A prophylactic or therapeutic method for cancer, which is characterized by selectively inhibiting ErbB-2 (HER2) to block information signals of multimers of the epithelial growth factor receptor family.
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- HETEROCYCLIC COMPOUNDS, OXAZOLE DERIVATIVES, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF
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This invention provides a heterocyclic compound having potent tyrosine kinase-inhibiting activity represented by the formula: wherein m is an integer of 1 to 3; n is an integer of 1 or 2; R1 is a halogen atom or an optionally halogenated C
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- MEDICINAL COMPOSITIONS IMPROVED IN SOLUBLITY IN WATER
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Solid dispersions are provided comprising an HER2 inhibitor which is hardly or not soluble in water and a hydrophilic polymer. These solid dispersions have been improved in the solubility of the HER2 inhibitor, oral absorption and bioavailability in blood
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Page/Page column 29
(2010/11/29)
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- MEDICINAL COMPOSITIONS HAVING IMPROVED ABSORBABILITY
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An HER2 inhibitor having an average particle size of about 3 μm or less or a composition containing the same which has improved HER2 inhibitor-absorbability.
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Page/Page column 34
(2010/11/29)
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- Method for producing 1-substituted-1,2,3- triazole derivative
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A method for producing a compound of the formula: (1) in a secondary or tertiary alcohol in the presence of a base, or (2) in the absence of a base is provided. According to this method, a 1-substituted-1,2,3-triazole compound having a tyrosine kinase inhibitory action can be produced efficiently in a high yield at an industrial large scale by a convenient method
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- Heterocyclic compounds their production and use
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A compound represented by the formula: wherein m is 1 or 2, R1 is a halogen or an optionally halogenated C1-2 alkyl; one of R2 and R3 is a hydrogen atom and the other is a group represented by the formula: wherein n is 3 or 4; R4 is a C1-4 alkyl group substituted by 1 or 2 hydroxy groups, or a salt thereof shows tyrosine kinase-inhibiting activity.
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- Structure and Photoisomerization of (E)- and (Z)-Cinnamamides and Their Lewis Acid Complexes
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The spectroscopic properties and photoisomerization reactions of several (E)- and (Z)-cinnamamides have been investigated in the absence and presence of the strong Lewis acid BF3.The (E)-cinnamamides are essentially planar and exist predominantly in the enone s-cis conformation, except in the case of the α-methyl tertiary amide which adopts the s-trans conformation in order to minimize nonbonded repulsion.The (Z)-cinnamamides exist predominantly in the highly nonplanar s-trans conformation.This unusual conformational preference is attributed to intramolecular charge transfer from the aromatic to amide functionality.Photoisomerization efficiencies are dependent upon N-alkylation, aromatic substitution, α-alkylation, and excitation wavelength.These effects are attributed to the existence of two lowest energy ?,?* singlet states (one reactive and one nonreactive) whose relative energies are dependent upon substitution.The cinnamamides form 1:1 complexes with BF3 with equilibrium constants >103.Complexation alters both the electronic structure and photochemical behavior of the cinnamamides.Quantitative E -> Z isomerization has been observed for the BF3 complexes of two tertiary amides.
- Lewis, Frederick D.,Elbert, Jeffrey E.,Upthagrove, Alana L.,Hale, Paul D.
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p. 553 - 561
(2007/10/02)
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