- Selective hydrolysis of phosphorus(v) compounds to form organophosphorus monoacids
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An azide and transition metal-free method for the synthesis of elusive phosphonic, phosphinic, and phosphoric monoacids has been developed. Inert pentavalent P(v)-compounds (phosphonate, phosphinate, and phosphate) are activated by triflate anhydride (Tf2O)/pyridine system to form a highly reactive phosphoryl pyridinium intermediate that undergoes nucleophilic substitution with H2O to selectively deprotect one alkoxy group and form organophosphorus monoacids.
- Ash, Jeffrey,Cordero, Paula,Huang, Hai,Kang, Jun Yong
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p. 6007 - 6014
(2021/07/21)
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- Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes
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Nrf2, which is a member of the cap'n’ collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation of anti-oxidant Nrf2 signaling may have therapeutic potential. A number of Nrf2 activators have entered into clinical trials. Nrf2 exists in the cytosol in complex with its binding partner Keap1, which is a thiol-rich redox-sensing protein. In response to oxidative and electrophilic stress, select cysteine residues of Keap1 are modified, which locks Keap1 in the Nrf2-Keap1 complex and allows newly synthesized Nrf2 to enter the nucleus. Numerous Nrf2-activating chemicals, including a number of natural products, are electrophiles that modify Keap1, often by Michael addition, leading to activation of Nrf2. One concern with the design of Nrf2 activators that are electrophilic covalent modifiers of Keap1 is the issue of selectivity. In the present study, substituted trans stilbenes were identified as activators of Nrf2. These activators of Nrf2 are not highly electrophilic and therefore are unlikely to activate Nrf2 through covalent modification of Keap1. Dose-response studies demonstrated that a range of substituents on either ring of the trans stilbenes, especially fluorine and methoxy substituents, influenced not only the sensitivity to activation, reflected in EC50values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2. The stilbene backbone appears to be a privileged scaffold for development of a new class of Nrf2 activators.
- Deck, Lorraine M.,Whalen, Lisa J.,Hunsaker, Lucy A.,Royer, Robert E.,Vander Jagt, David L.
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p. 1423 - 1430
(2017/02/18)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 00205
(2015/07/07)
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- Reductive coupling reactions: A new strategy for C(sp3)-P bond formation
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The C(sp3)-P bond forming reaction utilizing N-tosylhydrazones as readily available alkylating reagents was developed, which provides a new opportunity for preparing phosphine oxide derivatives with moderate to good yields. This reductive coupling reaction is proposed to proceed through an insertion of copper carbene into P-H bond of H-phosphorus oxides. The salient features of the reaction are operational simplicity and functional-group tolerance.
- Chen, Zi-Sheng,Zhou, Zhao-Zhao,Hua, Hui-Liang,Duan, Xin-Hua,Luo, Jian-Yi,Wang, Jia,Zhou, Ping-Xin,Liang, Yong-Min
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p. 1065 - 1068
(2013/02/25)
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- Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques
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Fluorescence probes that can detect Aβ (β-amyloid peptide) plaque are important tools for diagnosis of Alzheimer's disease (AD), and 4-N-methylamino-4′-hydroxystilbene (SB-13) is one of the promising candidate molecules. We report here the synthesis of SB-13 derivatives that consist of various electron donating/withdrawing moieties and distinct size of N-substituents. The synthesized compounds were screened for detection of Aβ40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and Aβ plaque imaging. Among these molecules, compound 42 meets two critical requirements for imaging agent; high fluorescence responsiveness and strong binding affinity. This compound showed more than 25-fold increase with the dissociation constant of 1.13 ± 0.37 μM. In AD mouse brain tissue, 42 selectively stained Aβ plaque, more specifically peripheral regions of Aβ plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies.
- Hong, Myeng Chan,Kim, Yun Kyung,Choi, Jae Yong,Yang, Si Qiang,Rhee, Hakjune,Ryu, Young Hoon,Choi, Tae Hyun,Cheon, Gi Jeong,An, Gwang Il,Kim, Hye Yun,Kim, Youngsoo,Kim, Dong Jin,Lee, Jun-Seok,Chang, Young-Tae,Lee, Kyo Chul
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experimental part
p. 7724 - 7730
(2011/01/13)
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- Synthesis, antitumor evaluation, and apoptosis-inducing activity of hydroxylated (E)-stilbenes
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The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)-stilbene analogues is described. In vitro screening revealed low micromolar activity (GI50) against the MDA MB 468 breast cancer cell line. Activity in MDA MB 468 cells correlated with the ability to induce apoptosis following drug treatment by the most potent agents in the series, e.g., 5dy and 5jy, an observation further reinforced by Annexin V-FITC analysis and fluorescence microscopy.
- Lion, Cedric J.,Matthews, Charles S.,Stevens, Malcolm F. G.,Westwell, Andrew D.
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p. 1292 - 1295
(2007/10/03)
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- Controlled monohalogenation of phosphonates: A new route to pure α- monohalogenated diethyl benzylphosphonates
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Starting from diethyl benzylphosphonates, a wide variety of diethyl α- monofluoro, chloro, bromo and iodobenzylphosphonates have been obtained in pure form by a one-pot procedure. This high yielding method implies the intermediate protection of the benzyl anion with TMSCI followed by halogenation with an electrophilic halogenating reagent.
- Iorga, Bogdan,Eymery, Frederic,Savignac, Philippe
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p. 2671 - 2686
(2007/10/03)
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- Use of benzylphosphonic acid derivatives for the treatment of diseases caused by viruses
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The use of a compound of the formula I STR1 in which V is an alkyl group, fluorine, chlorine, bromine, or iodine, n is an integer from 1 to 5, W is an alkyl, alkenyl, alkynyl or alkoxy group, cyanide, nitro, carboxyl, hydrogen or a cycloalkyl, aryl, aralkyl or carboalkoxy group, R1 and R2 are an alkyl, alkenyl, alkynyl, cycloalkyl or halogenoalkyl group, sodium, potassium, calcium, magnesium, aluminum, lithium, ammonium, triethylammonium or hydrogen, R1 and R2 together form a cyclic diester, R3 and R4 are an alkyl, alkenyl, alkynyl, carboalkoxy, cycloalkyl or alkoxy group, hydrogen, fluorine, chlorine, bromine or iodine and X, Y and Z are oxygen or sulfur, for the treatment of diseases caused by DNA viruses or RNA viruses is described.
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