The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> in good overall yields using an efficient and practical methodology in 3 steps has been implemented i...The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> in good overall yields using an efficient and practical methodology in 3 steps has been implemented in this present work. The first step was a heterocyclization between 2-hydroxybenzaldehyde <strong>1</strong> and propanedinitrile <strong>2</strong> which produced 2-iminocoumarin <strong>3</strong> which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine <strong>4</strong>. In the third step, reduction of <strong>5</strong> led to the desired 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6</strong>. Compounds <strong>5(a-d)</strong> and <strong>6(a-d)</strong> were evaluated for their potential <em>in vitro</em> cytotoxicity against six selected tumor cell lines (Huh7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and tested for their protein kinase inhibition on eight selected protein kinases. Among them, compounds <strong>5c</strong> and <strong>6b</strong> exhibited inhibition on HsCK1e (<strong>5c</strong>: 44% and <strong>6b</strong>: 42% at 1 μM) and <strong>5c </strong>for cytotoxicity on PC3 cell lines (63% at 25 μM).展开更多
The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by <s...The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by <sup>1</sup>H, <sup>13</sup>C NMR, FTIR, UV-Visible and HRMS. They were tested for their antiproliferative activities against six representative human tumor cell lines (Huh 7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and HaCat keratinocytes. Among them, compound 5e was active on HCT 116 (IC<sub>50</sub> 15 μM).展开更多
Abemaciclib (Verzerio<span style="white-space:nowrap;"><sup><span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">®</span>...Abemaciclib (Verzerio<span style="white-space:nowrap;"><sup><span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">®</span></sup></span>) is a cell cycle inhibitor of both CDK4 and CDK6. In 2017, abemaciclib was approved by the Food and Drug Administration (FDA) and, in 2018 by the European Medicines Agency (EMA) for the treatment of postmenopausal women with hormone receptor positive (HR<sup>+</sup>), human epidermal growth factor receptor 2 negative (HER2<sup><span style="white-space:nowrap;"><sup><span style="white-space:nowrap;">−</span></sup></span></sup>) advanced breast cancer. In this mini-review, we provide a series of information for respectively their targets and its selectivity, results on preclinical trial, clinical phase I, II and III trials, and some perspectives. We also describe the batch and flow steps used for the synthesis of this cancer drug.展开更多
This theoretical chemical reactivity study was conducted using the Density Functional Theory (DFT) method, at computational level B3LYP/6-31G (d). It involved a series of six (06) 5-arylidene rhodanines and allowed to...This theoretical chemical reactivity study was conducted using the Density Functional Theory (DFT) method, at computational level B3LYP/6-31G (d). It involved a series of six (06) 5-arylidene rhodanines and allowed to predict the chemical reactivity of these compounds. DFT global chemical reactivity descriptors (HOMO and LUMO energies, chemical hardness, softness, electronegativity) were examined to predict the relative stability and reactivity of rhodanin derivatives. Thus, the compound 6 which has an energy gap between the orbitals of ΔEgap = 3.004 eV is the most polarizable, the most reactive, the least stable, the best electron donor and the softest molecule. Calculation of the local indices of reactivity as well as dual descriptors revealed that the sulfur heteroatom of the Rhodanine ring is the privileged site of electrophilic attack in a state of sp3 hybridization and privileged site of nucleophilic attack in a state of sp2 hybridization.展开更多
文摘The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> in good overall yields using an efficient and practical methodology in 3 steps has been implemented in this present work. The first step was a heterocyclization between 2-hydroxybenzaldehyde <strong>1</strong> and propanedinitrile <strong>2</strong> which produced 2-iminocoumarin <strong>3</strong> which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine <strong>4</strong>. In the third step, reduction of <strong>5</strong> led to the desired 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6</strong>. Compounds <strong>5(a-d)</strong> and <strong>6(a-d)</strong> were evaluated for their potential <em>in vitro</em> cytotoxicity against six selected tumor cell lines (Huh7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and tested for their protein kinase inhibition on eight selected protein kinases. Among them, compounds <strong>5c</strong> and <strong>6b</strong> exhibited inhibition on HsCK1e (<strong>5c</strong>: 44% and <strong>6b</strong>: 42% at 1 μM) and <strong>5c </strong>for cytotoxicity on PC3 cell lines (63% at 25 μM).
文摘The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by <sup>1</sup>H, <sup>13</sup>C NMR, FTIR, UV-Visible and HRMS. They were tested for their antiproliferative activities against six representative human tumor cell lines (Huh 7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and HaCat keratinocytes. Among them, compound 5e was active on HCT 116 (IC<sub>50</sub> 15 μM).
文摘Abemaciclib (Verzerio<span style="white-space:nowrap;"><sup><span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">®</span></sup></span>) is a cell cycle inhibitor of both CDK4 and CDK6. In 2017, abemaciclib was approved by the Food and Drug Administration (FDA) and, in 2018 by the European Medicines Agency (EMA) for the treatment of postmenopausal women with hormone receptor positive (HR<sup>+</sup>), human epidermal growth factor receptor 2 negative (HER2<sup><span style="white-space:nowrap;"><sup><span style="white-space:nowrap;">−</span></sup></span></sup>) advanced breast cancer. In this mini-review, we provide a series of information for respectively their targets and its selectivity, results on preclinical trial, clinical phase I, II and III trials, and some perspectives. We also describe the batch and flow steps used for the synthesis of this cancer drug.
文摘This theoretical chemical reactivity study was conducted using the Density Functional Theory (DFT) method, at computational level B3LYP/6-31G (d). It involved a series of six (06) 5-arylidene rhodanines and allowed to predict the chemical reactivity of these compounds. DFT global chemical reactivity descriptors (HOMO and LUMO energies, chemical hardness, softness, electronegativity) were examined to predict the relative stability and reactivity of rhodanin derivatives. Thus, the compound 6 which has an energy gap between the orbitals of ΔEgap = 3.004 eV is the most polarizable, the most reactive, the least stable, the best electron donor and the softest molecule. Calculation of the local indices of reactivity as well as dual descriptors revealed that the sulfur heteroatom of the Rhodanine ring is the privileged site of electrophilic attack in a state of sp3 hybridization and privileged site of nucleophilic attack in a state of sp2 hybridization.