- Method for realizing N-alkylation by using alcohols as carbon source under photocatalysis
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The invention discloses a method for realizing N-alkylation by using alcohols as a carbon source under photocatalysis, and belongs to the technical field of catalytic synthesis. Alcohol, a substrate raw material and a catalyst are placed in a reaction device, ultraviolet and/or visible light irradiation is carried out in an inert atmosphere, after the irradiation is finished, solid-liquid separation is carried out to remove the catalyst, and an N-alkylation product can be obtained through extraction, distillation and purification, wherein the substrate raw material comprises any one of an amine compound, an aromatic nitro compound or an aromatic nitrile compound, the alcohol comprises any one or more of soluble primary alcohols, and the catalyst is metal oxide/titanium dioxide or metal sulfide/titanium dioxide. The method is simple and easy to operate, can be used for efficient photocatalysis one-pot multi-step hydrogenation N-alkylation reaction, and is mild in reaction condition, high in chemical selectivity of N-alkylamine, good in catalyst stability and easy to recycle.
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Paragraph 0048-0056; 0058
(2021/03/13)
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- Selective N -monomethylation of primary anilines with the controllable installation of N -CH2D, N -CHD2, and N -CD3units
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The selective N-monomethylation of primary anilines was realized by the use of the Me3N-BH3/N,N-dimethylformamide (DMF) system as the methyl source. This method also allows for the controllable introduction of N-CH2D, N-CHD2, and N-CD3 units with high lev
- Meng, Jing,Wang, Yi-Feng,Wang, Zhijuan,Xia, Hui-Min,Xu, Ai-Qing,Zhang, Feng-Lian
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supporting information
p. 4922 - 4926
(2020/07/30)
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- Highly Efficient Binuclear Copper-catalyzed Oxidation of N,N-Dimethylanilines with O2
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A binuclear copper-salicylate complex, [Cu(Sal)2(NCMe)]2 (Sal=salicylate), was found to be an active catalyst for the oxidation of N,N-dimethylanilines by O2, affording the corresponding N-methyl-N-phenylformamides as major products. The reactions were carried out with a O2 balloon and the S/C (substrate/catalyst ratio) of the model reaction could be up to 1×105, providing a practical and highly efficient catalytic protocol for accessing N-methyl-N-phenylformamides.
- Liu, Yuxia,Yan, Yonggang,Xue, Dong,Wang, Zhongfu,Xiao, Jianliang,Wang, Chao
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p. 2221 - 2225
(2020/03/23)
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- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
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Paragraph 001116; 001117
(2021/01/22)
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- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
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Paragraph 001158; 001159; 001160
(2019/07/17)
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- Binding Mode Characterization and Early in Vivo Evaluation of Fragment-Like Thiols as Inhibitors of the Virulence Factor LasB from Pseudomonas aeruginosa
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The increasing emergence of antibiotic resistance necessitates the development of anti-infectives with novel modes of action. Targeting bacterial virulence is considered a promising approach to develop novel antibiotics with reduced selection pressure. The extracellular collagenase elastase (LasB) plays a pivotal role in the infection process of Pseudomonas aeruginosa and therefore represents an attractive antivirulence target. Mercaptoacetamide-based thiols have been reported to inhibit LasB as well as collagenases from clostridia and bacillus species. The present work provides an insight into the structure-activity relationship (SAR) of these fragment-like LasB inhibitors, demonstrating an inverse activity profile compared to similar inhibitors of clostridial collagenase H (ColH). An X-ray cocrystal structure is presented, revealing distinct binding of two compounds to the active site of LasB, which unexpectedly maintains an open conformation. We further demonstrate in vivo efficacy in a Galleria mellonella infection model and high selectivity of the LasB inhibitors toward human matrix metalloproteinases (MMPs).
- Kany, Andreas M.,Sikandar, Asfandyar,Haupenthal, J?rg,Yahiaoui, Samir,Maurer, Christine K.,Proschak, Ewgenij,K?hnke, Jesko,Hartmann, Rolf W.
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p. 988 - 997
(2018/06/14)
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- Evaluation of 4-phenylamino-substituted naphthalene-1,2-diones as tubulin polymerization inhibitors
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A series of 4-phenylamino-substituted naphthalene-1,2-dione derivatives were prepared and evaluated as effective antiproliferative agents. MTT assays showed that the compounds with a methyl group on the nitrogen linker exhibited potent antiproliferative activities against human cancer cells. The mechanistic study revealed that these compounds could induce mitochondrial depolarization, which resulted in intracellular ROS production, and they also acted as tubulin polymerization inhibitors. Moreover, the typical compound could arrest A549 cells in the G2/M phase, resulting in cellular apoptosis and induced mitotic arrest in A549 cells through disrupting microtubule dynamics.
- Yang, Honghao,An, Baijiao,Li, Xingshu,Zeng, Wei
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p. 3057 - 3063
(2018/08/09)
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- Water Soluble Haloanilide Calcium-Release Calcium Channel Inhibitory Compounds and Methods to Control Bone Erosion and Inflammation Associated with Arthritides
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A compound that is selected from the group consisting of 3-(3,4-dichloroanilino)-3-oxopropanoic acid (hereinafter “DCOPA”); N-methyl-DCOPA; N,2-dimethyl-DCOPA; 2-methyl-DCOPA; isobutyl-DCOPA; N-methyl-isobutyl DCOPA; 3-(3,4-bibromoanilino)-3-oxopropanoic
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Paragraph 0085
(2017/09/23)
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- Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance
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The role of the G-protein-coupled bile acid receptor TGR5 in various organs, tissues, and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability. In this article, we describe their synthesis, characterization, and biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue, has low effect on gallbladder volume, and improves glucose homeostasis in a preclinical murine model of diet-induced obesity and insulin resistance, making the proof of concept of the potential of topical intestinal TGR5 agonists as therapeutic agents in type-2 diabetes.
- Lasalle, Manuel,Hoguet, Vanessa,Hennuyer, Nathalie,Leroux, Florence,Piveteau, Catherine,Belloy, Lo?c,Lestavel, Sophie,Vallez, Emmanuelle,Dorchies, Emilie,Duplan, Isabelle,Sevin, Emmanuel,Culot, Maxime,Gosselet, Fabien,Boulahjar, Rajaa,Herledan, Adrien,Staels, Bart,Deprez, Benoit,Tailleux, Anne,Charton, Julie
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p. 4185 - 4211
(2017/06/05)
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- IMIDAZOL- OR 1,2,4-TRIAZOL-DERIVATIVES AND THEIR USE
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The present invention is directed to novel compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.
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Page/Page column 64; 65
(2016/01/01)
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- USE OF UREA VARIANTS AS AFFINITY LIGANDS
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The present invention relates to an IgG-binding compound, which more specifically has affinity for human IgGs of k-type and functional derivatives thereof. More specifically, the compound according to the invention comprises an N,N-alkylated urea moiety l
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- 2,4-diaminopyridopyrimidine Inhibitors of Dihydrofolate Reductase from Pneumocystis carinii and Toxoplasma gondii
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Six previously unknown 2,4-diamino-6-(anilinomethyl)- and 2,4-diamino-6-pyridopyrimidines (5-10) were synthesized from 2,4-diamino-6-(bromomethyl)pyridopyrimidine hydrobromide (11*HBr) by treatment with the appropriate aniline or N-methylaniline in dimethylformamide at room temperature, with or without NaHCO3 present.Compounds 5-10 were tested as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, and rat liver as a part of a larger effort directed toward the discovery of lipophilic nonclassical antifolates combining high enzyme selectivity and high potency.Of the six analogues tested, the most potent and selective against T. gondii DHFR was 2,4-diamino-6-pyridopyrimidine (7), which had an IC50 of 0.0047 μM against this enzyme as compared with 0.026 μM against the rat liver enzyme.The potency of 7 against T. gondii DHFR was similar to that of trimetrexate (TMQ, 1) and piritrexim (PTX, 2) but was >500-fold greater than that of trimethoprim (TMP, 3).However, while 7 was more selective than either TMQ (19*) or PTX (63*) against this enzyme, its selectivity in comparison with TMP was 8-fold lower. 2,4-Diamino-6-pyridopyrimidine (6) was 17-fold less active than 7 and was also less selective. 2,4-Diamino-6-pyridopyrimidine (10) had an IC50 of 0.022 μM against P. carinii DHFR and was comparable in potency to TMQ and PTX.The species selectivity of 10 for P. carinii versus rat liver DHFR was greater than that of either TMQ (21-fold) or PTX (31-fold).On the other hand, even though 10 was slightly more active than TMQ against the P. carinii enzyme, its selectivity was 7-fold lower than that of TMP.Thus, the goal of combining high enzyme binding activity, which is characteristic of the fused-ring compounds TMQ and PTX, with high selectivity for T. gondii and P. carinii DHFR versus rat liver DHFR, which is characteristic of the monocyclic compound TMP, remained unmet in this limited series.
- Rosowsky, Andre,Forsch, Ronald A.,Queener, Sherry F.
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p. 2615 - 2620
(2007/10/03)
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