2315-36-8Relevant articles and documents
Antiprotozoal activity of bicyclic diamines with a N-methylpiperazinyl group at the bridgehead atom
Faist, Johanna,Seebacher, Werner,Kaiser, Marcel,Brun, Reto,Saf, Robert,Weis, Robert
, p. 4988 - 4996 (2013)
ω-Aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1-yl) bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2-azabicyclo[3.2. 2]nonanes were prepared and their activities were examined in vitro against the multiresistant K1 strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). Some of the newly synthesized compounds showed very promising antiprotozoal activity and selectivity. A few of the alkylamino-2-azabicyclo[3.2.2]nonanes exhibited high antiplasmodial activity, whereas a single bicyclo[2.2.2]octane derivative was the most potent antitrypanosomal compound. The results of the newly synthesized compounds were compared with the activities of already synthesized compounds and of drugs in use. Structure-activity relationships were discussed.
Novel selective and sensitive optical chemosensor based on phenylfluorone derivative for detection of Ge(IV) ion in aqueous solution
Keawwangchai, Somchai,Morakot, Nongnit,Keawwangchai, Tasawan
, p. 290 - 300 (2018)
A water soluble chemosensor for Ge4+ ion based on fluorone derivative containing 3,4?bis(2?(diethylamino)?2?oxoethoxy)phenyl (R8) has been synthesized. The binding abilities between R8 and 10 equiv. of Na+, K+, Ca2+, Fe2+, Cu2+, Cd2+, Hg2+, Pb2+, Al3+, Cr3+, Fe3+ and Ge4+ ions in 1% v/v EtOH-water (tris-buffer pH 7.0) were studied using UV–vis and fluorescence spectrophotometry. When observed by naked-eyes, the color of R8 changed from yellow-orange to pink and the fluorescent color changed from green to non-fluorescence when complexed with Ge4+ ion. The spectral analysis showed that UV–vis absorption and fluorescence emission intensity of R8 decreased dramatically when Ge4+ ion was added comparing with other ions. To explain this behavior, the quantum calculation was performed using the hybrid density functional at B3LYP /LanL2DZ level of theory. The calculated orbital energies indicated that the decreasing of UV–vis absorption and the quenching of fluorescence were due to the complexation induced metal to ligand charge transfer. The association constants (Ka) of R8-Ge4+ complexes calculated from Benesi–Hildebrand equation was 6.21 × 105 M?1. The UV–vis detection limit for Ge4+ was 4.40 × 10?7 M which was three orders of magnitude lower than those of Al3+, Cd2+, Cu2+ and Na+ ion.
Prodrugs of scutellarin: Ethyl, benzyl and N,N-diethylglycolamide ester synthesis, physicochemical properties, intestinal metabolism and oral bioavailability in the rats
Cao, Feng,Guo, Jian-Xin,Ping, Qi-Neng,Liao, Zheng-Gen
, p. 385 - 393 (2006)
In an effort to enhance the oral bioavailability of scutellarin, ethyl, benzyl and N,N-diethylglycolamide ester of scutellarin were synthesized. The hydrolysis of the prodrugs follows first-order kinetics in aqueous solution, and produced a V-shaped pH profile. The N,N-diethylglycolamide ester is highly susceptible to enzymatic hydrolysis in human plasma (t1/2 ≈ 7 min) with a high stability in aqueous solution (t1/2 ≈ 16 day, pH 4.2). Compared with the solubility of scutellarin, the solubility of glycolamide ester was about ten times in pH 4.0 buffer, and about thirty five times in water. Its apparent partition coefficient increased significantly from -2.56 to 1.48. Glycolamide ester of scutellarin was chosen to investigate the intestinal metabolism and in vivo bioavailability. Degradation studies in the intestinal tract content and homogenates indicated intestinal metabolism before absorption was a crucial obstacle for the prodrug. N,N-Diethylglycolamide ester can be protected from the degradation in the intestinal lumen by an emulsion. A significant increase in the plasma AUC and Cmax of the prodrug emulsion was observed in rats, compared with that of the scutellarin-cyclodextrin complex (P 0.01). The emulsion of N,N-diethylglycolamide ester produces a 1.58-fold enhancement in apparent bioavailability and 1.4-fold increase in the absolute bioavailability compared to the scutallarin-cyclodextrin complex.
Preparation method of N,N-diethyl chloroacetamide
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Paragraph 0052; 0055-0065, (2021/03/13)
The invention relates to a preparation method of N,N-diethyl chloroacetamide, which comprises the steps of adding 423+/-2 parts of dichloromethane into a reaction kettle, adding 90+/-0.5 parts of diethylamine, dropwisely adding 69.7+/-0.5 parts of chloroacetyl chloride into the reaction kettle under the temperature control condition of 5+/-5 DEG C, keeping the temperature at 5+/-5 DEG C, stirringfor 180+/-10 minutes, and adding 128.3+/-2 parts of water into the reaction kettle, stirring, standing for layering, taking an organic layer, adding 62.3+/-1 parts of water and 23.2+/-0.5 parts of sodium chloride, stirring, standing for layering, taking the organic layer, recovering dichloromethane, and discharging to obtain the product. The method for preparing N,N-diethyl chloroacetamide is simple and convenient to operate and high in yield, and the prepared finished product is high in purity and low in content of related substances.
De novo Design of SARS-CoV-2 Main Protease Inhibitors
Dovala, Dustin,Fischer, Christian,Nomura, Daniel K.,Peitsinis, Zisis,Spradlin, Jessica N.,Trauner, Dirk,Yang, Chao,Zhang, Yingkai,Rühmann, Klaus-Peter,Vep?ek, Nynke A.
supporting information, (2021/10/16)
The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, M Pro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.
Palladium-Catalyzed β-C(sp3)-H Arylation of Aliphatic Ketones Enabled by a Transient Directing Group
Wang, Yangyang,Wu, Gaorong,Xu, Xiaobo,Pang, Binghan,Liao, Shaowen,Ji, Yafei
, p. 7296 - 7303 (2021/05/29)
The direct arylation of aliphatic ketones has been developed via Pd-catalyzed β-C(sp3)-H bond functionalization with 2-(aminooxy)-N,N-dimethylacetamide as a novel transient directing group (TDG), which showed remarkable directing ability to generate arylated products in moderate to good yields. Furthermore, the reaction can tolerate abundant substrate of ketones and aryl iodides. This study expands the scope of applications for TDGs.
Quinazoline derivative and application thereof as antitumor drug
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Paragraph 0102-0105, (2020/08/22)
The invention belongs to the technical field of medicinal chemistry, and relates to a quinazoline derivative shown as a general formula (I), physiologically acceptable salt formed by the quinazoline derivative and inorganic or organic acid, a pharmaceutical composition containing the quinazoline derivative and the physiologically acceptable salt, and application of the quinazoline derivative and the pharmaceutical composition to preparation of drugs for treating tumor diseases, particularly drugs for treating abnormal EGFR family diseases. The compound has pharmacological properties with important values, and especially has an inhibition effect on signal transduction caused by tyrosine kinase.
Design and synthesis of some barbituric and 1,3-dimethylbarbituric acid derivatives: A non-classical scaffold for potential PARP1 inhibitors
Eldin A. Osman, Essam,Hanafy, Noura S.,George, Riham F.,El-Moghazy, Samir M.
, (2020/09/16)
Six series based on barbituric acid 5a-e, 10a-d; thiobarbituric acid 6a-e, 11a-d and 1,3-dimethylbarbituric acid 7a-e, 12a-d were prepared and screened for their in vitro PARP1 inhibition. They revealed promising inhibition at nanomolar level especially compounds 5c, 7b, 7d and 7e (IC50 = 30.51, 41.60, 41.53 and 36.33 nM) with higher potency than olaparib (IC50 = 43.59 nM). Moreover, compounds 5b, 5d, 7a, 12a and 12c exhibited good comparable activity (IC50 = 65.93, 58.90, 66.57, 45.40 and 50.62 nM, respectively). Furthermore, the most active compounds 5c, 7b, 7d, 7e, 12a and 12c against PARP1 in vitro were evaluated in the BRCA1 mutated triple negative breast cancer cell line MDA-MB-436 where 5c and 12c showed higher potency compared to olaparib and result in cell cycle arrest at G2/M phase. 5c and 12c showed apoptotic effects in MDA-MB-436 and potentiated the cytotoxicity of temozolomide in A549 human lung epithelial cancer cell line. Compounds 5c and 12c represent interesting starting points towards PARP1 inhibitors.
Discovery and Optimization of Glucose Uptake Inhibitors
Liu, Kevin G.,Kim, Ji-In,Olszewski, Kellen,Barsotti, Anthony M.,Morris, Koi,Lamarque, Christophe,Yu, Xuemei,Gaffney, Jack,Feng, Xiao-Jiang,Patel, Jeegar P.,Poyurovsky, Masha V.
supporting information, p. 5201 - 5211 (2020/07/10)
Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.
Catalytic hydrogenation of α,β-unsaturated carboxylic acid derivatives using copper(i)/N-heterocyclic carbene complexes
Zimmermann, Birte M.,Kobosil, Sarah C. K.,Teichert, Johannes F.
supporting information, p. 2293 - 2296 (2019/02/27)
A simple and air-stable copper(i)/N-heterocyclic carbene complex enables the catalytic hydrogenation of enoates and enamides, hitherto unreactive substrates employing homogeneous copper catalysis and H2 as a terminal reducing agent. This atom economic transformation replaces commonly employed hydrosilanes and can also be carried out in an asymmetric fashion.
