Day: November 24, 2022

Hancock, Michael K. published the artcileMulti-pathway cellular analysis of compound selectivity, Application of SU6656, the publication is Molecular BioSystems (2010), 6(10), 1834-1843, database is CAplus and MEDLINE.

Signaling pathways and their protein target constituents (e.g. kinases) have become important therapeutic targets in many disease areas. Traditional selectivity profiling for kinase inhibitors has relied upon screening panels of recombinant enzymes in biochem. assay formats. Recent studies have highlighted the importance of using cellular assays to better approx. true biol. selectivity. We have developed a portfolio of CellSensor beta-lactamase transcriptional reporter gene assays that can be used to screen for perturbagens of various endogenous signaling pathways. Here we describe a multi-pathway profiling approach for generating compound-pathway selectivity maps. To demonstrate the utility of this approach, we have screened 32 known compounds across a diverse panel of 12 key signaling pathways and generated the first comprehensive cellular pathway selectivity profiles of several clin. approved kinase and other well-known bioactive inhibitors. Selectivity score comparisons identified several kinase inhibitors that were more promiscuous than predicted by traditional biochem. profiling methods. For example, we identified effects of sorafenib on the JAK/STAT pathway and demonstrated the potential therapeutic indication of sorafenib in treating leukemia/myeloproliferative disorder patients harboring TEL-JAK2 or JAK2V617F mutations. Our results indicate that multi-pathway profiling can efficiently characterize both on and off-pathway compound activities, revealing potential novel pathways and opportunities for drug repositioning purposes and/or safety liabilities in one profiling campaign.

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, 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

Loerke, Dinah published the artcileQuantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation, Quality Control of 330161-87-0, the publication is Science Signaling (2012), 5(231), rs5, 13 pp., database is CAplus and MEDLINE.

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image anal. tools that do not require fluorescence tagging and that automatically track and characterize three aspects of scattering in live cells: increase in cell motility, loss of cell-cell adhesion and spatial dispersion of cells (the redistribution of cells during scattering). We used these tools to screen a library of drugs and we identified several efficient inhibitors of scattering, which we classified as selective inhibitors of either motility or loss of cell-cell adhesion, or as nonselective inhibitors. We validated the inhibitors and putative targets from this screen in two unrelated model cell lines. Using pharmacol. treatments and RNA interference (RNAi), we found that nonsteroidal anti-inflammatory drugs inhibited cell-cell dissociation, that indirubins inhibited cell motility and that cyclin-dependent kinase 1 and ribosomal S6 kinase were signaling intermediates in HGF-induced cell scattering. This assay is suitable for larger-scale screenings of chem. compounds or RNAi libraries.

Science Signaling 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, Quality Control 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

Vantourout, Julien C. published the artcileChan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem, SDS of cas: 837392-67-3, the publication is Journal of Organic Chemistry (2016), 81(9), 3942-3950, database is CAplus and MEDLINE.

The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan-Evans-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C-N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines.

Journal of Organic Chemistry published new progress about 837392-67-3. 837392-67-3 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Amide,Boronate Esters,Aliphatic Heterocyclic, name is tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxylate, and the molecular formula is C9H6N2O2, SDS of cas: 837392-67-3.

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

Lukashev, Nikolay V. published the artcile6-Chloro- and 6-bromo-substituted steroids in the Suzuki-Miyaura cross-coupling reaction. A convenient route to potential aromatase inhibitors, SDS of cas: 149108-61-2, the publication is Synthesis (2006), 533-539, database is CAplus.

Chlorine at an sp²-carbon in steroids was shown to be reactive in Suzuki-Miyaura cross-coupling reactions with either Ni or Pd catalysts. The coupling of analogous 6-bromo derivatives was also demonstrated to be applicable to a wider scope of substrates. The Suzuki-Miyaura arylation of 6-bromo-螖^3,5-steroid enol ethers with subsequent hydrolysis is a useful route to 6-arylated steroids bearing aryl at a saturated carbon.

Synthesis 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 C15H14BNO4S, SDS of cas: 149108-61-2.

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

Dolusic, Eduard published the artcileIndol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors, SDS of cas: 20538-12-9, the publication is Bioorganic & Medicinal Chemistry (2011), 19(4), 1550-1561, database is CAplus and MEDLINE.

Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathol. immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biol. activities have been evaluated, leading to compounds with IC₅₀ values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biol. activity, thus corroborating the virtual screening results.

Bioorganic & Medicinal 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, SDS of cas: 20538-12-9.

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

Maybruck, Brian T. published the artcileThe aminoalkylindole BML-190 negatively regulates chitosan synthesis via the cyclic AMP/protein kinase A1 pathway in Cryptococcus neoformans, Application In Synthesis of 2854-32-2, the publication is mBio (2019), 10(6), e02264, database is CAplus and MEDLINE.

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immunocompromising conditions. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify addnl. genes/proteins that influence chitosan biosynthesis. To identify these compounds, we developed a robust and novel cell-based flow cytometry screening method to identify small-mol. inhibitors of chitosan production We screened the ICCB Known Bioactives library and identified 8 compounds that reduced chitosan in C. neoformans. We used flow cytometry-based counterscreens and confirmatory screens, followed by a biochem. secondary screen to refine our primary screening hits to 2 confirmed hits. One of the confirmed hits that reduced chitosan content was the aminoalkylindole BML-190, a known inverse agonist of mammalian cannabinoid receptors. We demonstrated that BML-190 likely targets the C. neoformans G-protein-coupled receptor Gpr4 and, via the cAMP (cAMP)/protein kinase A (PKA) signaling pathway, contributes to an intracellular accumulation of cAMP that results in decreased chitosan. Our discovery suggests that this approach could be used to identify addnl. compounds and pathways that reduce chitosan biosynthesis and could lead to potential novel therapeutics against C. neoformans.

mBio published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Application In Synthesis of 2854-32-2.

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

Krishnamoorthy, Ravi published the artcilePalladium-Catalyzed Preparation of Weinreb Amides from Boronic Acids and N-Methyl-N-methoxycarbamoyl Chloride, Product Details of C15H14BNO4S, the publication is Journal of Organic Chemistry (2010), 75(4), 1251-1258, database is CAplus and MEDLINE.

A simple protocol for the synthesis of Weinreb benzamides and 伪,尾-unsaturated Weinreb amides through a palladium-catalyzed cross-coupling reaction between organoboronic acids and N-methoxy-N-methylcarbamoyl chloride has been developed. The method is also applicable to the use of potassium organotrifluoroborates.

Journal of Organic Chemistry 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 C15H14BNO4S, Product Details of C15H14BNO4S.

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

Gorle, Simhachalam published the artcileA Simple and Efficient [(n-Bu₃Sn)₂MO₄]_n Catalyzed Synthesis of Quinazolinones and Dihydroquinazolinones, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde, the publication is Polycyclic Aromatic Compounds, database is CAplus.

A novel unprecedented approach for the synthesis of various quinazolinones and dihydroquinazolinones using [(n-Bu₃Sn)₂MO4]_n as a catalyst is discussed. The reaction was carried out in various solvents and a gram scale experiment was demonstrated under the given conditions. Further, the substrate scope of the reaction and the recyclability of the catalyst were studied.

Polycyclic Aromatic Compounds 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, Recommanded Product: 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

Martic, S. published the artcileElectrochemical investigations of sarcoma-related protein kinase inhibition, COA of Formula: C19H21N3O3S, the publication is Electrochimica Acta (2011), 56(28), 10676-10682, database is CAplus.

An electrochem. biosensor was developed for the determination of sarcoma (Src)-related protein kinase-catalyzed phosphorylation reactions in the presence of adenosine 5′-纬-ferrocenoyl triphosphate (Fc-ATP). The sensing platform is based on a highly specific amino acid sequence Glu-Gly-Ile-Tyr-Asp-Val-Pro (EGIYDVP), to which a Fc-PO₂ moiety can be transferred from Fc-ATP by the action of the Src kinase. The enzyme kinetics and kinase inhibition were investigated by square wave voltammetry (SWV). The kinetic parameters K_m and V_max were determined for Src protein kinase with respect to Fc-ATP co-substrate and were found to be 200 渭M and 115 渭A cm^-2 min, for phosphorylation of the EGIYDVP peptide substrate. Furthermore, the Src-catalyzed phosphorylation of Tyr was investigated in the presence of the small mol. inhibitors PP1, PP2, SU6656, and roscovitine. PP3 does not inhibit Src activity and was used as a control. The percent inhibition at half concentration, IC₅₀, values were determined for all inhibitors under the study and were estimated to be in the 5-30 nM range. The electrochem. study suggests that the increase in inhibition efficiency was in the order PP3 < SU6656 < roscovitine < PP2 < PP1.

Electrochimica Acta 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, COA of Formula: 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

Karishin, A. P. published the artcileCondensation of 5-chloro-6-fluoroacenaphthenequinone with 3-hydroxythionaphthene, its derivatives, and indoxyl, HPLC of Formula: 2642-37-7, the publication is Zhurnal Obshchei Khimii (1964), 34(9), 306-8, database is CAplus.

Indigoid dyes of structure I were prepared, where X is S or NH, R¹ is H or Me, R² is H, or R¹ + R² is benzo, and R³ is H, Cl, or OEt. 5-Chloro-6- fluoroacenaphthene (10 g.) in 150 ml. HOAc was heated to 100掳, 50 g. Na₂Cr₂O₇ was added, heating continued 4 min., and the mixture poured into 300 ml. H₂O. The precipitate was filtered, washed, and heated twice with 300 ml. 6% NaHC0₃ solution on a boiling water bath for 40 min. 4,5,1,8-ClFC₁₀H₄(CO₂H)₂ (II), precipitated by acidifying the alk. solution with HCl, was filtered and dried to yield 3.1 g. colorless needles of II anhydride (III), m. 234-5掳 (HOAc). The filtrate from the isolation of III was treated twice with 50 ml. 25% NaHSO₃. The resulting compound was decomposed with HCl, and the mixture was boiled to remove SO₂, then cooled, filtered, and dried to give 3.41 g. 5-chloro-6-fluoronaphthenequinone (IV) golden yellow needles, m. 241-2. To 0.01 mole IV in 50 ml. boiling HOAc were added 0.01 mole 3-hydroxythionaphthene and 5 drops concentrated HCl, and the mixture was boiled 5 min., cooled, and filtered to give 88.2% I (R¹ = R² = R³ = H, X = S), m. 284-5掳(PhNO₂)₂, 位max. 492 and 535 m渭. Other I (X = S) were prepared similarly (R¹, R₂, R₃, % yield, m.p., and 位_max in 渭 (PhCl) given): H, H, Cl, 81.5, 375-6掳, 480 and 515; Me, H, Cl, 77.3, 334-5%, 482 and 517; H, H, OEt, 61.2, 271-2掳 460 and 496; R¹ + R² = benzo, H, 61.5, 337-8掳, 464 and 510. To 2.34 g. IV in 50 ml. boiling HOAc was added a filtered solution of 18.6 g. 7% indoxyl melt in 60 ml. 70% HOAc. The mixture was boiled 5 min., then cooled to give 2.6 g. (74.4%) I (R¹ = R² = R³ = H, X = NH), m. 324-5掳 (PhNO₂), 位_max 552 and 571 m渭.

Zhurnal Obshchei Khimii published new progress about 2642-37-7. 2642-37-7 belongs to indole-building-block, auxiliary class Indole,Salt,Sulfonate,Inhibitor,Inhibitor, name is Potassium 1H-indol-3-yl sulfate, and the molecular formula is C8H6KNO4S, HPLC of Formula: 2642-37-7.

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