- Regorafenib analogues and their ferrocenic counterparts: Synthesis and biological evaluation
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Approved by the FDA in 2012, regorafenib is one of the last chance treatments for colorectal cancer. While various analogues have already been prepared, ferrocenic derivatives have never been evaluated. In this study, we prepared various ferrocene-containing derivatives of regorafenib and recorded their biological activity in kinase and cellular assays. This led to the identification of a squaramide derivative which shows a good cellular activity and three ferrocene analogues with promising activity in both kinase and cellular assays. This journal is
- Wilde, Myron,Arzur, Danielle,Baratte, Blandine,Lefebvre, Dorian,Robert, Thomas,Roisnel, Thierry,Le Jossic-Corcos, Catherine,Bach, Stéphane,Corcos, Laurent,Erb, William
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p. 19723 - 19733
(2020/12/04)
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- Dioxane quinazoline and dioxane quinazoline type compound, and preparation method and application thereof
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The invention relates to a dioxane quinazoline and dioxane quinazoline type compound having a formula (I) as described in the specification or a pharmaceutically acceptable salt thereof. The inventionalso provides preparation of the compound having the formula (I) and the pharmaceutically acceptable salt and application of the compound and the pharmaceutically acceptable salt as a medicine. The medicine is used as a tyrosine kinase (such as VEGFR-2, c-MET and RET) inhibitor for treating diseases relevant to tyrosine kinases.
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Paragraph 0069-0071; 0072-0073
(2020/03/17)
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- Direct conversion of carboxylic acids to various nitrogen-containing compounds in the one-pot exploiting curtius rearrangement
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Herein we report, a single-pot multistep conversion of inactivated carboxylic acids to various N-containing compounds using a common synthetic methodology. The developed methodology rendered the use of carboxylic acids as a direct surrogate of primary amines, for the synthesis of primary ureas, secondary/tertiary ureas, O/S-carbamates, benzoyl ureas, amides, and N-formyls, exploiting the Curtius reaction. This approach has a potential to provide a diversified library of N-containing compounds, starting from a single carboxylic acid, based on the selection of the nucleophile.
- Kumar, Arun,Kumar, Naveen,Sharma, Ritika,Bhargava, Gaurav,Mahajan, Dinesh
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p. 11323 - 11334
(2019/09/10)
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- Characterization of degradation products of regorafenib by LC-QTOF-MS and NMR spectroscopy: Investigation of rearrangement and odd-electron ion formation during collision-induced dissociations under ESI-MS/MS
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Regorafenib is an oral multikinase inhibitor, and it was subjected to stress conditions (hydrolysis, oxidative, thermal and photolytic) as per ICH specified conditions. The drug showed considerable degradation under hydrolysis (acidic, basic and neutral) and oxidative stress conditions, whereas it was stable under other stress conditions. A total of five degradation products (DPs) were observed and these were analyzed by using a UHPLC-DAD system. Chromatographic separation was achieved on an Acquity CSH C18 column (100 × 2.1 mm, 1.7 μ) using 0.1% formic acid and acetonitrile:methanol (80:20%, v/v) as the mobile phase in gradient mode. All DPs were characterized by LC-MS/MS, and the major degradation product (DP1) was isolated by using an HPLC preparative system from a degradation mixture and analyzed using NMR (1D and 2D NMR) and IR experiments. It was observed that protonated DP1 and DP3 undergo rearrangement reactions during collision-induced dissociations under positive electrospray ionization conditions. Additionally, in silico toxicity of the drug and its degradation products (DP1-DP5) was evaluated using TOPKAT and DEREK toxicity prediction software tools.
- Baira, Shandilya Mahamuni,Srinivasulu, Gannoju,Nimbalkar, Rakesh,Garg, Prabha,Srinivas,Talluri, M.V.N. Kumar
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p. 12091 - 12103
(2017/10/16)
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- SORAFENIB ANALOGS AND USES THEREOF
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The present invention provides, inter alia, compounds according to formula I. Also provided are pharmaceutical compositions and kits containing such compounds. Methods for using such compounds, compositions, and kits for treating a subject having system xc-, dysregulation for activating ferroptosis, for inhibiting system xc- in a cell, and for monitoring treatment of a subject having system xc- dysregulation are provided as well.
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Paragraph 0140; 0183
(2015/04/22)
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