Day: November 21, 2022

Schiwek, Christian H. published the artcileDiastereoselective Rhodium-Catalyzed Hydrogenation of 2-Oxindoles and 3,4-Dihydroquinolones, HPLC of Formula: 837392-64-0, the publication is Organic Letters (2020), 22(24), 9468-9472, database is CAplus and MEDLINE.

The benzene ring of indolin-2-ones (2-oxindoles) and 3,4-dihydroquinol-2-ones was converted to a saturated cyclohexane ring by hydrogenation in the presence of the rhodium complex ^Cy(CAAC)Rh(cod)Cl. The stereoselectivity of the process was found to be high with respect to both external substituent R¹ within the saturated part of the heterocyclic ring and substituent X on the benzene ring. Twenty-one hexahydroindolin-2(3H)-ones (70-99% yield, dr = 83/17 to >99/1) and twelve octahydro-2(1H)-quinolinones (87-96% yield, dr = 64/36 to >99/1) were obtained with the major diastereoisomer exhibiting the hydrogen atoms in an all-cis arrangement. The high tolerance toward functional groups and the compatibility with existing stereogenic centers are key features of the hydrogenation protocol presented here.

Organic Letters published new progress about 837392-64-0. 837392-64-0 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Amide,Boronate Esters, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one, and the molecular formula is C14H18BNO3, HPLC of Formula: 837392-64-0.

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

Riffell, Jenna L. published the artcileCaspase-3-Dependent Mitotic Checkpoint Inactivation by the Small-Molecule Inducers of Mitotic Slippage SU6656 and Geraldol, Product Details of C19H21N3O3S, the publication is Molecular Cancer Therapeutics (2011), 10(5), 839-849, database is CAplus and MEDLINE.

Microtubule-targeting cancer drugs such as paclitaxel block cell-cycle progression at mitosis by prolonged activation of the mitotic checkpoint. Cells can spontaneously escape mitotic arrest and enter interphase without chromosome segregation by a process termed mitotic slippage that involves the degradation of cyclin B1 without mitotic checkpoint inactivation. Inducing mitotic slippage with chems. causes cells to die after multiple rounds of DNA replication without cell division, which may enhance the antitumor activity of microtubule-targeting drugs. Here, we explore pathways leading to mitotic slippage by using SU6656 and geraldol, two recently identified chem. inducers of mitotic slippage. Mitotic slippage induced by SU6656 or geraldol was blocked by the proteasome inhibitor MG-132 and involved proteasome-dependent degradation of cyclin B1 and the mitotic checkpoint proteins budding uninhibited by benzimidazole related 1 (BubR1) and cell division cycle 20 (Cdc20) in T98G cells. Mitotic slippage and the degradation of BubR1 and Cdc20 were also inhibited by the caspase-3 and -7 inhibitor DEVD-CHO. MCF-7 cells lacking caspase-3 expression could not degrade BubR1 or undergo mitotic slippage in response to SU6656 or geraldol. Introduction of caspase-3 completely restored the ability of MCF-7 cells to degrade BubR1 and undergo mitotic slippage. However, lack of expression of caspase-3 did not affect cell death after exposure to paclitaxel, with or without mitotic slippage induction. The requirement for caspase-3 for chem. induced mitotic slippage reveals a new mechanism for mitotic exit and a link between mitosis and apoptosis that has implications for the outcome of cancer chemotherapy. Mol Cancer Ther; 10(5); 839-49.

Molecular Cancer Therapeutics 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, Product Details of C19H21N3O3S.

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

Pang, Yadong published the artcileIridium(I)-Catalyzed C-H Borylation in Air by Using Mechanochemistry, Recommanded Product: 5-Methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Chemistry – A European Journal (2019), 25(18), 4654-4659, database is CAplus and MEDLINE.

Mechanochem. has been applied for the first time to an iridium(I)-catalyzed C-H borylation reaction. By using either none or just a catalytic amount of a liquid, the mechanochem. C-H borylation of a series of heteroaromatic compounds proceeded in air to afford the corresponding arylboronates in good-to-excellent yields. A one-pot mechanochem. C-H borylation/Suzuki-Miyaura cross-coupling sequence for the direct synthesis of 2-aryl indole derivatives is also described. The present study constitutes an important milestone towards the development of industrially attractive solvent-free C-H bond functionalization processes in air.

Chemistry – A European Journal published new progress about 683229-62-1. 683229-62-1 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Ether,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 5-Methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO3, Recommanded Product: 5-Methoxy-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

Pang, Yadong published the artcileIridium(I)-Catalyzed C-H Borylation in Air by Using Mechanochemistry, Category: indole-building-block, the publication is Chemistry – A European Journal (2019), 25(18), 4654-4659, database is CAplus and MEDLINE.

Mechanochem. has been applied for the first time to an iridium(I)-catalyzed C-H borylation reaction. By using either none or just a catalytic amount of a liquid, the mechanochem. C-H borylation of a series of heteroaromatic compounds proceeded in air to afford the corresponding arylboronates in good-to-excellent yields. A one-pot mechanochem. C-H borylation/Suzuki-Miyaura cross-coupling sequence for the direct synthesis of 2-aryl indole derivatives is also described. The present study constitutes an important milestone towards the development of industrially attractive solvent-free C-H bond functionalization processes in air.

Chemistry – A European Journal published new progress about 1256358-91-4. 1256358-91-4 belongs to indole-building-block, auxiliary class Indole,Chloride,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 5-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H17BClNO2, Category: indole-building-block.

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

Kilic, Zuhal published the artcileEvaluation of new indole and bromoindole derivatives as pp60^c-Src tyrosine kinase inhibitors, Application of SU6656, the publication is Chemical Biology & Drug Design (2009), 74(4), 397-404, database is CAplus and MEDLINE.

A series of N-benzyl-indole-3-imine-, amine derivatives and their 5-bromo congeners were synthesized and their biol. activity were evaluated against the pp60^c-Src tyrosine kinase target. To afford the imine derivatives, aldehydes were reacted with substituted benzylamines and the corresponding amine derivatives were obtained by NaBH₄ reduction of these imines. Except insoluble N-benzyl-indole-3-imine derivatives, all the derivatives showed some activity against the kinase target. Screening of these compounds for their biol. activity revealed that among N-benzylindole derivatives, those bearing 5-bromo substitution have the enhanced potency, where the amine derivatives were more active than imines.

Chemical Biology & Drug Design 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 of 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

Tani, Masanobu published the artcileSynthetic studies of indoles and related compounds. XXX. Regioselective bromination of methoxy derivatives of ethyl indole-2-carboxylate, Category: indole-building-block, the publication is Heterocycles (1992), 34(12), 2349-62, database is CAplus.

Bromination of Et methoxyindole-2-carboxylates I (R = H, R¹ = 4-, 5-, 6-, 7-OMe) with bromine in acetic acid proceeded on the benzene moiety of I, whereas the reaction of I with pyridinium bromide perbromide in pyridine or N-bromosuccinimide in DMF gave 3-bromo derivatives I (R = Br).

Heterocycles 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 C5H13Cl2N, Category: indole-building-block.

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

White, James D. published the artcileTandem Photocycloaddition-Retro-Mannich Fragmentation of Enaminones. A Route to Spiropyrrolines and the Tetracyclic Core of Koumine, Quality Control of 167015-84-1, the publication is Organic Letters (2006), 8(6), 1081-1084, database is CAplus and MEDLINE.

Intramol. [2+2] photocycloaddition of β-aminoalkylidene malonates gives transiently a cyclobutane which undergoes retro-Mannich fragmentation to a Δ¹-pyrroline. The tandem sequence, exemplified in two series based on tryptamine and aminoethyl-1,4-cyclohexadiene, leads to a spiroindolopyrroline skeleton (I) and to the nonindolenine portion (II) of koumine.

Organic Letters published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C6H10O7, Quality Control of 167015-84-1.

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

Johnson, Ronald L. published the artcileA quantitative high-throughput screen for modulators of IL-6 signaling: A model for interrogating biological networks using chemical libraries, Synthetic Route of 330161-87-0, the publication is Molecular BioSystems (2009), 5(9), 1039-1050, database is CAplus and MEDLINE.

Small mol. modulators are critical for dissecting and understanding signaling pathways at the mol. level. Interleukin 6 (IL-6) is a cytokine that signals via the JAK-STAT pathway and is implicated in cancer and inflammation. To identify modulators of this pathway, we screened a chem. collection against an IL-6 responsive cell line stably expressing a β-lactamase reporter gene fused to a sis-inducible element (SIE-bla cells). This assay was optimized for a 1536-well microplate format and screened against 11 693 small mols. using quant. high-throughput screening (qHTS), a method that assays a chem. library at multiple concentrations to generate titration-response profiles for each compound The qHTS recovered 564 actives with well-fit curves that clustered into 32 distinct chem. series of 13 activators and 19 inhibitors. A retrospective anal. of the qHTS data indicated that single concentration data at 1.5 and 7.7 μM scored 35 and 71% of qHTS actives, resp., as inactive and were therefore false negatives. Following counter screens to identify fluorescent and non-selective series, we found four activator and one inhibitor series that modulated SIE-bla cells but did not show similar activity in reporter gene assays induced by EGF and hypoxia. Small mols. within these series will make useful tool compounds to investigate IL-6 signaling mediated by JAK-STAT activation.

Molecular BioSystems 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, 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

Lin, Kai-Chun published the artcileInhibition of AMPK through Lyn-Syk-Akt enhances FcεRI signal pathways for allergic response, Recommanded Product: SU6656, the publication is Journal of Molecular Medicine (Heidelberg, Germany) (2016), 94(2), 183-194, database is CAplus and MEDLINE.

AMPK was shown to neg. regulate FcεRI activation, and FcεR-mediated Fyn activation can counteract the LKB1/AMPK axis in mast cells. However, the relationship between the major Src family kinase Lyn and AMPK remains poorly defined. Here, we investigate the mol. mechanism for AMPK inhibition by FcεRI-Lyn signaling in rat RBL-2H3 cells. We found that FcεRI activation could rapidly inhibit AMPK activation through increased AMPK phosphorylation at the inhibitory Ser485/491 residues without a change at the activating Th172 residue, and this was accompanied by a reduction of ACC phosphorylation. Using specific inhibitors and gene silencing, we found that such AMPK inhibition involved a signaling cascade through Lyn-Syk-Akt. When AMPK was activated by AICAR, A769662 and metformin, FcεRI-mediated Syk, ERK, JNK and p38 activation, and TNFα release were all inhibited. Consistently, AMPK inhibition by compound C increased FcεRI-mediated Lyn activation. Moreover, AMPK activation dominantly impaired IgE-induced recruitment of signal proteins to the FcεRI by blocking the formation of FcεRIβ-Lyn-Syk, FcεRIγ-Lyn-Syk, and AMPK-FcεRIβ complexes. In vitro kinase assay further revealed the ability of AMPKα2 to phosphorylate FcεRIβ in the complex. In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE. In summary, our findings demonstrate that IgE-mediated FcεRI activation results in AMPK inhibition through activation of Lyn-Syk-Akt pathway, and as such FcεRI receptor can efficiently propagate Lyn-mediated allergic signaling and response. These results provide important insights into the use of AMPK activators for the treatment of allergic diseases. AMPK is inhibited by FcεRI via Lyn-Syk-Akt signaling in RBL-2H3 cells. AMPK inhibition supports FcεRI-mediated Lyn signaling and allergic response. Metformin has inhibitory effect on passive cutaneous anaphylaxis.

Journal of Molecular Medicine (Heidelberg, Germany) 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

Chang, Hua-Ching published the artcileSpleen tyrosine kinase mediates the actions of EPO and GM-CSF and coordinates with TGF-β in erythropoiesis, HPLC of Formula: 330161-87-0, the publication is Biochimica et Biophysica Acta, Molecular Cell Research (2017), 1864(4), 687-696, database is CAplus and MEDLINE.

Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biol. actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis. Notably, unlike Syk, Src family kinases are not involved in the viability control of TF-1 cells. Signaling studies showed that Syk is required for STAT5 and ERK activation induced by EPO, and Akt and ERK activation induced by GM-CSF. Nevertheless, R406 does not change the Smad2/3 signal caused by TGF-β, and TGF-β neither affects above signal pathways of EPO and GM-CSF. Of note, Syk is constitutively associated with EPOR in plasma membrane and can bind to STAT5 at active status upon EPO stimulation. Furthermore, EPO-induced Hb γ expression was reduced by R406. In BFU-E and CFU-E colony formation assays in Syk-deficient erythroid progenitor cells, we confirmed the essential role of Syk in erythropoiesis mediated by EPO. Taken together, Syk is a novel upstream signaling mol. of EPOR, and contributes to erythroblast proliferation, survival and differentiation.

Biochimica et Biophysica Acta, Molecular Cell Research 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, HPLC of Formula: 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