Day: November 21, 2022

Pirovano, Valentina published the artcileGold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides, Safety of 5-Fluoro-1H-indole-2-carbaldehyde, the publication is Chemical Communications (Cambridge, United Kingdom) (2013), 49(34), 3594-3596, database is CAplus and MEDLINE.

A gold-catalyzed formal [4+2] cycloaddition of vinyl indoles and N-allenamides leading to tetrahydrocarbazoles is described. E.g., in presence of AuCl₃, [4+2] cycloaddition of vinyl indole (I) and N-allenamide (II) gave 83% tetrahydrocarbazole derivative (III). Moreover, new multicomponent reactions of vinyl indoles with two allene mols. are reported.

Chemical Communications (Cambridge, United Kingdom) published new progress about 220943-23-7. 220943-23-7 belongs to indole-building-block, auxiliary class Indole,Fluoride,Aldehyde, name is 5-Fluoro-1H-indole-2-carbaldehyde, and the molecular formula is C9H6FNO, Safety of 5-Fluoro-1H-indole-2-carbaldehyde.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Anastassiadis, Theonie published the artcileComprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity, Recommanded Product: SU6656, the publication is Nature Biotechnology (2011), 29(11), 1039-1045, database is CAplus and MEDLINE.

Small-mol. protein kinase inhibitors are widely used to elucidate cellular signaling pathways and are promising therapeutic agents. Owing to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments that use these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we used functional assays to profile the activity of 178 com. available kinase inhibitors against a panel of 300 recombinant protein kinases. Quant. anal. revealed complex and often unexpected interactions between protein kinases and kinase inhibitors, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can identify multitargeted inhibitors of specific, diverse kinases. The results have implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments involving kinase inhibitors.

Nature Biotechnology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Recommanded Product: SU6656.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Vancraenenbroeck, Renee published the artcileIn silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2, Synthetic Route of 330161-87-0, the publication is Frontiers in Molecular Neuroscience (2014), 00051, database is CAplus and MEDLINE.

A review. Leucine-rich repeat kinase 2 (LRRK2) is a complex, multidomain protein which is considered a valuable target for potential disease-modifying therapeutic strategies for Parkinson’s disease (PD). In mammalian cells and brain, LRRK2 is phosphorylated and treatment of cells with inhibitors of LRRK2 kinase activity can induce LRRK2 dephosphorylation at a cluster of serines including Ser910/935/955/973. It has been suggested that phosphorylation levels at these sites reflect LRRK2 kinase activity, however kinase-dead variants of LRRK2 or kinase activating variants do not display altered Ser935 phosphorylation levels compared to wild type. Furthermore, Ser910/935/955/973 are not autophosphorylation sites, therefore, it is unclear if inhibitor induced dephosphorylation depends on the activity of compounds on LRRK2 or on yet to be identified upstream kinases. Here we used a panel of 160 ATP competitive and cell permeable kinase inhibitors directed against all branches of the kinome and tested their activity on LRRK2 in vitro using a peptide-substrate-based kinase assay. In neuronal SH-SY5Y cells overexpressing LRRK2 we used compound-induced dephosphorylation of Ser935 as readout. In silico docking of selected compounds was performed using a modeled LRRK2 kinase structure. Receiver operating characteristic plots demonstrated that the obtained docking scores to the LRRK2 ATP binding site correlated with in vitro and cellular compound activity. We also found that in vitro potency showed a high degree of correlation to cellular compound induced LRRK2 dephosphorylation activity across multiple compound classes. Therefore, acute LRRK2 dephosphorylation at Ser935 in inhibitor treated cells involves a strong component of inhibitor activity on LRRK2 itself, without excluding a role for upstream kinases. Understanding the regulation of LRRK2 phosphorylation by kinase inhibitors aids our understanding of LRRK2 signaling and may lead to development of new classes of LRRK2 kinase inhibitors.

Frontiers in Molecular Neuroscience published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C10H15ClO3S, Synthetic Route of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jin, Shengfei published the artcileVisible Light-Induced Borylation of C-O, C-N, and C-X Bonds, Name: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society (2020), 142(3), 1603-1613, database is CAplus and MEDLINE.

Aryl phosphates, arylammonium salts and aryl halides were borylated with B₂pin₂ in photochem. substitution reaction catalyzed by phenothiazines, yielding aryl pinacolboranes and aryltrifluoroborates. Boronic acids are centrally important functional motifs and synthetic precursors. Visible light-induced borylation may provide access to structurally diverse boronates, but a broadly efficient photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C-O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron-rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reaction exhibits excellent functional group tolerance, as demonstrated by the borylation of a range of structurally complex substrates. Remarkably, the reaction is catalyzed by phenothiazine, a simple organic photocatalyst with MW < 200 that mediates the previously unachievable visible light-induced single electron reduction of phenol derivatives with reduction potentials as neg. as approx. – 3 V vs. SCE by a proton-coupled electron transfer mechanism. Mechanistic studies point to the crucial role of the photocatalyst-base interaction.

Journal of the American Chemical Society published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Name: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Liu, Hong published the artcileDesign and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase, Name: 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(24), 126104, database is CAplus and MEDLINE.

Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic benzofuran-based structures were prepared and evaluated. Similar to clin. developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclin. animal species. To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clin. relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.

Bioorganic & Medicinal Chemistry Letters published new progress about 1256359-96-2. 1256359-96-2 belongs to indole-building-block, auxiliary class Indole,Fluoride,Boronic acid and ester,Boronic Acids,Boronate Esters,Boronate Esters, name is 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H17BFNO2, Name: 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Reigan, Philip published the artcileDevelopment of Indolequinone Mechanism-Based Inhibitors of NAD(P)H:Quinone Oxidoreductase 1 (NQO1): NQO1 Inhibition and Growth Inhibitory Activity in Human Pancreatic MIA PaCa-2 Cancer Cells, Synthetic Route of 192820-78-3, the publication is Biochemistry (2007), 46(20), 5941-5950, database is CAplus and MEDLINE.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is currently an emerging target in pancreatic cancer. In this report, we describe a series of indolequinones, based on 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), and evaluate NQO1 inhibition and growth inhibitory activity in the human pancreatic MIA PaCa-2 tumor cell line. The indolequinones with 4-nitrophenoxy, 4-pyridinyloxy, and acetoxy substituents at the (indol-3-yl)methyl position were NADH-dependent inhibitors of recombinant human NQO1, indicative of mechanism-based inhibition. However, those with hydroxy and phenoxy substituents were poor inhibitors of NQO1 enzyme activity, due to attenuated elimination of the leaving group. The ability of this series of indolequinones to inhibit recombinant human NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells. The examination of indolequinone interactions in complex with NQO1 from computational-based mol. docking simulations supported the observed biochem. data with respect to NQO1 inhibition. The design of both NQO1-inhibitory and non-inhibitory indolequinone analogs allowed us to test the hypothesis that NQO1 inhibition was required for growth inhibitory activity in MIA PaCa-2 cells. ES936 and its 6-methoxy analog were potent inhibitors of NQO1 activity and cell proliferation; however, the 4-pyridinyloxy and acetoxy compounds were also potent inhibitors of NQO1 activity but relatively poor inhibitors of cell proliferation. In addition, the phenoxy compounds, which were not inhibitors of NQO1 enzymic activity, demonstrated potent growth inhibition. These data demonstrate that NQO1 inhibitory activity can be dissociated from growth inhibitory activity and suggest addnl. or alternative targets to NQO1 that are responsible for the growth inhibitory activity of this series of indolequinones in human pancreatic cancer.

Biochemistry published new progress about 192820-78-3. 192820-78-3 belongs to indole-building-block, auxiliary class Fused/Partially Saturated Cycles,Dihydroindoles, name is 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, and the molecular formula is C18H16N2O6, Synthetic Route of 192820-78-3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Tsai, Henry J. published the artcileA novel hydroxyfuroic acid compound as an insulin receptor activator – structure and activity relationship of a prenylindole moiety to insulin receptor activation, Safety of (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Journal of Biomedical Science (London, United Kingdom) (2009), No pp. given, database is CAplus and MEDLINE.

Background: Diabetes Mellitus is a chronic disease and many patients of which require frequent s.c. insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far. Methods: A series of hydroxyfuroic acid compounds were synthesized and tested for their efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this study. Results and conclusions: This study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potent as compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a moderate inhibitor to EGF receptor. Structure and activity relationship of the prenylindole moiety to insulin receptor activation is discussed.

Journal of Biomedical Science (London, United Kingdom) published new progress about 149108-61-2. 149108-61-2 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-tosyl-1H-Indol-3-yl)boronic acid, and the molecular formula is C6H12F3NO5S, Safety of (1-tosyl-1H-Indol-3-yl)boronic acid.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Paul, Sulagna published the artcileIr-catalyzed functionalization of 2-substituted indoles at the 7-position: Nitrogen-directed aromatic borylation, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society (2006), 128(49), 15552-15553, database is CAplus and MEDLINE.

Ir-catalyzed borylation of 2-substituted indoles selectively yielded 7-borylated products, e.g., I (R = H, Cl or OMe) in good yields. N-Protection, required for previous functionalizations of 2-substituted indoles, was unnecessary.

Journal of the American Chemical Society published new progress about 919119-59-8. 919119-59-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO2, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Hieda, Yuhzo published the artcileTotal Synthesis of the Neuronal Cell-Protecting Carbazole Alkaloids Carbazomadurin A and (S)-(+)-Carbazomadurin B, COA of Formula: C12H13NO3, the publication is European Journal of Organic Chemistry (2013), 2013(32), 7391-7401, database is CAplus.

The total syntheses of the neuronal cell-protecting carbazole alkaloids carbazomadurin A and (S)-(+)-carbazomadurin B, I [R = Me, (S)-Et, resp.], were achieved. The key step of the synthesis of the polysubstituted carbazole rings included an allene-mediated electrocyclic reaction of the 6π-electron system that involved the indole 2,3-bond. The cleavage of the alkoxy groups of the resulting 3-ethoxy-8-isopropoxycarbazole successfully gave the 3,8-dihydroxycarbazole, which was converted into the 3,8-bis(OSEM)-carbazole (SEM = 2-trimethylsilylethoxymethyl). A Suzuki-Miyaura cross-coupling reaction of the 3,8-bis(OSEM)-carbazole with the corresponding alkenyl pinacol borates afforded the 1-alkenylcarbazoles, which were treated with tetra-n-butylammonium fluoride (TBAF) followed by reduction with NaBH₄ to provide carbazomadurin A and (S)-(+)-carbazomadurin B, resp.

European Journal of Organic Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, COA of Formula: C12H13NO3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ku, Kyung-Eun published the artcileSrc inhibition induces melanogenesis in human G361 cells, Application In Synthesis of 330161-87-0, the publication is Molecular Medicine Reports (2019), 19(4), 3061-3070, database is CAplus and MEDLINE.

The Src kinase family (SKF) includes non-receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, and is involved in the progression of cellular transformation and oncogenic activity. Therefore, the present study investigated whether C-terminal Src kinase inhibition can induce melanogenesis and examined the associated signaling pathways and mRNA expression of melanogenic proteins. First, whether stimulators of melanogenesis, such as UV B and a-MSH, can dephosphorylate Src protein was evaluated, and the results revealed that SU6656 and PP2 inhibited the phosphorylation of Src in G361 cells. Src inhibition by these chem. inhibitors induced melanogenesis in G361 cells and upregulated the mRNA expression levels of melanogenesis-associated genes encoding microphthalmia-associated transcription factor, tyrosinase-related protein 1 (TRP1), TRP2, and tyrosinase. In addition, Src inhibition by small interfering RNA induced melanogenesis and upregulated the mRNA expression levels of melanogenesis-associated genes. As the p38 mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element binding (CREB) pathways serve key roles in melanogenesis, the present study further examined whether Src mediates melanogenesis via these pathways. Taken together, these data indicate that Src is associated with melanogenesis, and Src inhibition induces melanogenesis via the MAPK and CREB pathways in G361 cells.

Molecular Medicine Reports published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Application In Synthesis of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles