- Photorearrangement of Quinoline-Protected Dialkylanilines and the Photorelease of Aniline-Containing Biological Effectors
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The direct release of dialkylanilines was achieved by controlling the outcome of a photorearrangement reaction promoted by the (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ) photoremovable protecting group. The substrate scope was investigated to obtain structure-activity relationships and to propose a reaction mechanism. Introducing a methyl substituent at the 2-methyl position of the CyHQ core enabled the bypass of the photorearrangement and significantly improved the aniline release efficiency. We successfully applied the strategy to the photoactivation of mifepristone (RU-486), an antiprogestin drug that is also used to induce the LexPR gene expression system in zebrafish and the gene-switch regulatory system based on the pGL-VP chimeric regulator in mammals.
- Deodato, Davide,Asad, Naeem,Dore, Timothy M.
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- Synthesis of metapristone through an efficient: N -demethylation of mifepristone
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Accumulating evidence demonstrates that mifepristone (RU486) exhibits potent anti-proliferative effects on various cancer cell lines. Our recent work shows that its major metabolite metapristone (RU42633) is a good drug candidate for cancer metastatic che
- Wu, Jianlei,Yu, Xuemei,Liu, Jian,Lin, Yuqin,Gao, Yu,Jia, Lee,Chen, Haijun
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- Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer
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Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers currently with a lack of targeted therapeutic drugs. Accumulating evidence supports that KLF5 represents a novel therapeutic target for the treatment of basal TNBC. Our previ
- Lin, Yuqi,Liu, Rong,Zhao, Ping,Ye, Jinxiang,Zheng, Zheng,Huang, Jingan,Zhang, Yingying,Gao, Yu,Chen, Haiying,Liu, Suling,Zhou, Jia,Chen, Ceshi,Chen, Haijun
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Read Online
- Bacterial Biosynthetic P450 Enzyme PikCD50N: A Potential Biocatalyst for the Preparation of Human Drug Metabolites
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Human drug metabolites (HDMs) are important chemicals widely used in drug-related studies. However, acquiring these enzyme-derived and regio-/stereo-selectively modified compounds through chemical approaches is complicated. PikC is a biosynthetic P450 enz
- Cheng, Fangyuan,Du, Lei,Durairaj, Pradeepraj,Guo, Jiawei,Li, Fengwei,Li, Shengying,Liu, Xiaohui,Long, Xiangtian,Ma, Li,Tang, Dandan,Zhang, Gang,Zhang, Wei,Zhang, Xingwang
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p. 14563 - 14571
(2021/11/12)
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- ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS
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The disclosure relates to anti-cancer compounds which are anti-cancer PARP inhibitors of formula Al, A2, A3 or A4 conjugated by a linker to a steroid, whereby the steroid targets the conjugate to the nucleus, as well as to methods for their preparation and use. (I)
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Page/Page column 129-130
(2021/05/21)
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- Preparation method of metapristone
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The invention provides a new and simple synthesis method of metapristone. Metapristone is adopted as the starting material, ferrous phthalocynine is taken as the catalyst, and acetic acid and tert-butyl hydroperoxide are employed as the reaction reagents
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Paragraph 0013; 0014; 0015; 0016; 0017; 0018
(2018/05/01)
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- Acetic Acid Accelerated Visible-Light Photoredox Catalyzed N-Demethylation of N,N-Dimethylaminophenyl Derivatives
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N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible-light photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture. (Figure presented.).
- Wu, Guolin,Li, Yazhen,Yu, Xuemei,Gao, Yu,Chen, Haijun
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supporting information
p. 687 - 692
(2017/02/23)
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- Synthesis, in vitro progesterone receptors affinity of gadolinium containing mifepristone conjugates and estimation of binding sites in human breast cancer cells
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Novel gadolinium-based mifepristone conjugates were synthesised using various synthetic routes. Moderate antiprogestagenic activity of the new conjugates was observed in human breast cancer cells (T47-D cells) using AP (alkaline phosphatase) assay. The amount of incorporated Gd determined by inductively coupled plasma mass spectroscopy (ICPMS) indicates the number of binding sites per cell. These conjugates might be important compounds to develop receptor-targeted MRI contrast agents as well as other anti-breast cancer therapeutics.
- Saha, Pijus,H?dl, Claudia,Strauss, Wolfgang S.L.,Steiner, Rudolf,Goessler, Walter,Kunert, Olaf,Leitner, Alexander,Haslinger, Ernst,Schramm, H. Wolfgang
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experimental part
p. 1891 - 1898
(2010/05/17)
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- Syntheses and antigestagenic activity of mifepristone derivatives
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A series of mifepristone derivatives with different "linker groups" in position 4' of the phenyl ring in the 11β- position of the steroid scaffold (2-41) have been synthesized. Their antigestagenic activites were determined in a cell-based assay (alkali p
- H?dl, Claudia,Raunegger, Katrin,Strommer, Rainer,Ecker, Gerhard F.,Kunert, Olaf,Sturm, Sonja,Seger, Christoph,Haslinger, Ernst,Steiner, Rudolf,Strauss, Wolfgang S. L.,Schramm, Hans-Wolfgang
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supporting information; scheme or table
p. 1268 - 1274
(2009/12/26)
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- Liver-selective glucocorticoid antagonists: A novel treatment for type 2 diabetes
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Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes.
- Von Geldern, Thomas W.,Tu, Noah,Kym, Philip R.,Link, James T.,Jae, Hwan-Soo,Lai, Chunqiu,Apelqvist, Theresa,Rhonnstad, Patrik,Hagberg, Lars,Koehler, Konrad,Grynfarb, Marlena,Goos-Nilsson, Annika,Sandberg, Johnny,Osterlund, Marie,Barkhem, Tomas,H?glund, Marie,Wang, Jiahong,Fung, Steven,Wilcox, Denise,Nguyen, Phong,Jakob, Clarissa,Hutchins, Charles,F?rnegf?rdh, Mathias,Kauppi, Bj?rn,?hman, Lars,Jacobson, Peer B.
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p. 4213 - 4230
(2007/10/03)
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- GLUCOCORTICOID RECEPTOR LIGANDS FOR THE TREATMENT OF METABOLIC DISORDERS
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This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.
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- Liver specific bile acid derivatives of the glucocorticoid antagonist RU486
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Novel glucocorticoid receptor ligands and methods of treating diseases such as diabetes, wherein the ligands have general formula (I) STR1wherein the variables are as defined by the present specification.
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- Synthesis of N-desmethyl derivatives of 17α-acetoxy-11β(4-N,N- dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione and mifepristone: Substrates for the synthesis of radioligands
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The syntheses of N-desmethyl derivatives of CDB-2914 and the mono-N- desmethyl derivative of Mifepristone are described. We also describe the use of the mono-desmethyl derivatives as substrates for the synthesis of N- tritomethyl derivatives of CDB-2914 a
- Rao, Pemmaraju N.,Acosta, C. Kirk,Cessac, James W.,Bahr, Martin L.,Kim, Hyun K.
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p. 205 - 212
(2007/10/03)
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- Synthesis and characterization of tritium-labelled RU486
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[3H]RU38486 (RU486) was synthesized from its penultimate precursor, desmethyl RU486, by substitution of the secondary amine with tritiated methyl iodide; specific activity 85 Ci/mmol. Ligand binding studies confirm that RU486 binds with high affinity to human progesterone receptor type A (PR-A) and progesterone receptor type B (PR-B).
- Mais,Chen,Wagoner,Scott Hayes,Wang
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p. 1199 - 1203
(2007/10/03)
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