Day: November 25, 2022

Soderberg, Bjorn C. G. published the artcileIntramolecular cyclization reactions of unsaturated amino Fischer chromium carbenes forming indoles and quinolines, Product Details of C11H11NO2, the publication is Tetrahedron (2003), 59(44), 8775-8791, database is CAplus.

A thermally induced intramol. annulation reaction of N-(2-alkenylphenyl)amino substituted Fischer chromium carbenes has been extensively examined The carbene complexes were prepared in moderate to good yields by reaction of 2-aminostyrenes with intermediately formed acyloxy substituted carbenes. Upon heating, the thermally labile carbenes decomposed producing indoles and quinolines as the major products. The product distribution was found to be highly dependent on the substitution pattern and electronic properties of the starting material, and on the solvent used. The reaction of pentacarbonyl[1-[[2-ethenyl-3-(methoxycarbonyl)phenyl]amino]ethylidene]chromium gave 2-methyl-1H-indole-4-carboxylic acid Me ester. The reaction of pentacarbonyl[1-[[2-(1-methylethenyl)phenyl]amino]ethylidene]chromium gave 2,4-dimethylquinoline and 1,2,3,4-tetrahydro-2,4-dimethylquinoline.

Tetrahedron published new progress about 57663-18-0. 57663-18-0 belongs to indole-building-block, auxiliary class Indole,Ester, name is Methyl 2-methyl-1H-indole-5-carboxylate, and the molecular formula is C3H5BN2O2, Product Details of C11H11NO2.

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

Grinshtain, Elina published the artcileThe Fer tyrosine kinase protects sperm from spontaneous acrosome reaction, Related Products of indole-building-block, the publication is Developmental Biology (Amsterdam, Netherlands) (2022), 24-33, database is CAplus and MEDLINE.

The physiol. acrosome reaction occurs after mammalian spermatozoa undergo a process called capacitation in the female reproductive tract. Only acrosome reacted spermatozoon can penetrate the egg zona-pellucida and fertilize the egg. Sperm also contain several mechanisms that protect it from undergoing spontaneous acrosome reaction (sAR), a process that can occur in sperm before reaching proximity to the egg and that abrogates fertilization. We previously showed that calmodulin-kinase II (CaMKII) and phospholipase D (PLD) are involved in preventing sAR through two distinct pathways that enhance F-actin formation during capacitation. Here, we describe a novel addnl. pathway involving the tyrosine kinase Fer in a mechanism that also prevents sAR by enhancing actin polymerization during sperm capacitation. We further show that protein-kinase A (PKA) and the tyrosine-kinase Src, as well as PLD, direct Fer phosphorylation/activation. Activated Fer inhibits the Ser/Thr phosphatase PP1, thereby leading to CaMKII activation, actin polymerization, and sAR inhibition.

Developmental Biology (Amsterdam, Netherlands) 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, Related Products of 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

Yan, Chao published the artcilePotent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target, Computed Properties of 192820-78-3, the publication is Molecular Pharmacology (2009), 76(1), 163-172, database is CAplus and MEDLINE.

The indolequinone ES936 {5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione} was previously developed in our laboratory as an antitumor agent against pancreatic cancer. The objective of this study was to identify indolequinones with improved potency against pancreatic cancer and to define their mechanisms of action. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and BxPC-3 were used in in vitro assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) and clonogenic assays]; indolequinones displayed potent cytotoxicity against all three cell lines, and two specific classes of indole-quinone were particularly potent agents. These indolequinones induced caspase-dependent apoptosis but no redox cycling or oxidative stress in MIA PaCa-2 and BxPC-3 cells. Selected indolequinones were also screened against the NCI-60 cell line panel and were found to be particularly effective against colon, renal, and melanoma cancer cells. A potential target of these indolequinones was identified as thioredoxin reductase. Indolequinones were found to be potent inhibitors of thioredoxin reductase activity both in pancreatic cancer cells and in cell-free systems. The mechanism of action of the indolequinones was shown to involve metabolic reduction, loss of a leaving group to generate a reactive electrophile resulting in alkylation of the selenocysteine residue in the active site of thioredoxin reductase. In vivo efficacy of the indolequinones was also tested in the MIA PaCa-2 pancreatic tumor xenograft in nude mice, and lead indolequinones demonstrated high efficacy and low toxicity. Inhibition of thioredoxin reductase represents a potential novel target in pancreatic cancer and may provide a biomarker of effect of lead indolequinones in this type of cancer.

Molecular Pharmacology 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 C5H5F3O2, Computed Properties 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

Lv, Handeng published the artcileAn UPLC-MS/MS method for the determination of EAI045 in plasma and tissues and its application to pharmacokinetic and distribution studies in rats, Quality Control of 1942114-09-1, the publication is Pharmazie (2018), 73(11), 630-634, database is CAplus and MEDLINE.

EAI045 represents a fourth generation allosteric EGFR TKI compound which targets T790M and C797S EGFR mutants. The study reported herein describes a method to explore the distribution of EAI045 in rat tissues as well as to quantify it in plasma. The method used here is an ultra-performance liquid chromatog.-tandem mass spectrometry with high sensitivity and selectivity. An ACQUITY UPLC BEN HILIC column with dimensions of 2.1 × 100 mm, 1.7 mum was used to sep. the analytes and IS. As mobile phase acetonitrile as well as 0.1% of formic acid/water was used combined with an elution gradient and 0.40 mL/min flow rate. This eluent was also used for electrospray ionization in pos. ion mode. A mode on multiple reactions monitoring (MRM) was also employed in the quantification. This quantification included the use of targeted segment ions with m/z 384.1 100.8 for EAI045, and m/z 285.1 193.3 for IS, resp. It was found that the linearity of this method was appropriate and the concentration range could be kept within a range of 2-2000 ng/mL for EAI045 in rat plasma and tissues. The level of EAI045 was found to be highest in the liver, followed by kidneys, lungs and heart. Furthermore, the results provided evidence that EAI045 could be absorbed quickly and distributed widely in different tissue types.

Pharmazie published new progress about 1942114-09-1. 1942114-09-1 belongs to indole-building-block, auxiliary class Indoline,Thiazole,Fluoride,Amine,Benzene,Amide,Alcohol,Protein Tyrosine Kinase/RTK, name is 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, and the molecular formula is C19H14FN3O3S, Quality Control of 1942114-09-1.

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

Norton, Charles E. published the artcileAugmented pulmonary vasoconstrictor reactivity after chronic hypoxia requires Src kinase and epidermal growth factor receptor signaling, Computed Properties of 330161-87-0, the publication is American Journal of Respiratory Cell and Molecular Biology (2020), 62(1), 61-73, database is CAplus and MEDLINE.

We tested the hypothesis that Src-epidermal growth factor receptor (EGFR) signaling mediates enhanced vasoconstrictor sensitivity after chronic hypoxia through NADPH oxidase-derived superoxide generation. Protocols employed pharmacol. inhibitors in isolated, pressurized rat pulmonary arteries to examine the contribution of a variety of signaling moieties to enhanced vascular tone after chronic hypoxia. Superoxide generation in pulmonary arterial smooth muscle cells was assessed using the fluorescent indicator dihydroethidium. Indexes of pulmonary hypertension were measured in rats treated with the EGFR inhibitor gefitinib. Inhibition of NADPH oxidase, Rac1 (Ras-related C3 botulinum toxin substrate 1), and EGFR abolished pressure-induced pulmonary arterial tone and endothelin-1 (ET-1)-dependent calcium sensitization and vasoconstriction after chronic hypoxia. Src kinases were also activated by ET-1 after chronic hypoxia and contributed to enhanced basal arterial tone and vasoconstriction in response to ET-1. A role for matrix metalloproteinase 2 to mediate Src-dependent EGFR activation is further supported by our findings. Our studies support a novel role for an Src kinase-EGFR-NADPH oxidase signaling axis to mediate enhanced pulmonary vascular smooth muscle Ca21 sensitization, vasoconstriction, and pulmonary hypertension after chronic hypoxia.

American Journal of Respiratory Cell and Molecular Biology 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, Computed Properties 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

Wright, Jay S. published the artcileSequential Ir/Cu-Mediated Method for the Meta-Selective C-H Radiofluorination of (Hetero)Arenes, HPLC of Formula: 2304635-05-8, the publication is Journal of the American Chemical Society (2021), 143(18), 6915-6921, database is CAplus and MEDLINE.

This article describes a sequential Ir/Cu-mediated process for the meta-selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp²)-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [¹⁸F]tetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochem. yield and radiochem. purity. This entire process is performed on a bench top without Schlenk or glove box techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FX_FN module with 1,3-dimethoxybenzene and a meta-tyrosine derivative The products, [¹⁸F]1-fluoro-3,5-dimethoxybenzene and an ¹⁸F-labeled meta-tyrosine derivative, were obtained in 37 ± 5% isolated radiochem. yield and >99% radiochem. purity and 25% isolated radiochem. yield and 99% radiochem. purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity (A_m), resp.

Journal of the American Chemical Society published new progress about 2304635-05-8. 2304635-05-8 belongs to indole-building-block, auxiliary class Boronate Esters,Boronic Acids,Boronic acid and ester, name is Methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-4-carboxylate, and the molecular formula is C10H23N, HPLC of Formula: 2304635-05-8.

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

Wu, Xingxin published the artcileEpigallocatechin-3-gallate sensitizes IFN-γ-stimulated CD4⁺ T cells to apoptosis via alternative activation of STAT1, Computed Properties of 330161-87-0, the publication is International Immunopharmacology (2014), 23(2), 434-441, database is CAplus and MEDLINE.

Epigallocatechin-3-gallate (EGCG) exerts anti-inflammatory properties on immune cells and binds to CD4 mols. However, the effects of EGCG on CD4⁺ T cells remain largely unknown. Here, we found that EGCG enhanced IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) activation in primary CD4⁺ T cells from C57BL/6 mice and in a human leukemic CD4⁺ T-cell line of Hut 78 cells, while it inhibited the classical pathway of IFN-γ signaling including activating phosphorylations of Janus kinase (JAK) 1, JAK2 and STAT3, forming interferon-γ activated sequence (GAS)-binding STAT1 homodimers, and producing pro-inflammatory chemokine (C-X-C motif) ligand 9 (CXCL9). CD4 blockade did not suppress the increase in IFN-γ-induced STAT1 activation in CD4⁺ T cells by EGCG. Furthermore, activation of Src kinase was also triggered by IFN-γ plus EGCG in both Hut 78 and primary CD4⁺ T cells. Interestingly, EGCG promoted apoptosis of CD4⁺ T cells treated with IFN-γ. The increases in STAT1 activation and apoptosis induced by EGCG in IFN-γ-activated CD4⁺ T cells were almost completely abolished by a selective Src family kinase inhibitor, SU6656. Moreover, EGCG alleviates CD4⁺ CD45RB^hi CD25^– T cell transfer induced colitis with less accumulation of CD4⁺ T cells in the colon. In conclusion, the present study reports an alternative activation of STAT1 via Src by EGCG in IFN-γ-activated CD4⁺ T cells, which promotes the apoptosis of IFN-γ-activated CD4⁺ T cells and contributes to the improvement of T cell-mediated colitis. Our findings suggest a novel role of EGCG in regulating IFN-γ signaling and controlling inflammation.

International Immunopharmacology 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 C16H24BF4Ir, Computed Properties 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

Bert, Giancarlo published the artcileThe nitration of 3-indolecarboxyaldehyde and ethyl 3-indoleglyoxylate, HPLC of Formula: 10242-03-2, the publication is Gazzetta Chimica Italiana (1961), 728-41, database is CAplus.

A suspension of 1 g. 3-indolecarboxaldehyde (I) in 8 ml. AcOH treated with 1.05 ml. HNO₃ (d. 1.37), heated to 80° until an exothermic reaction began, and cooled rapidly gave 0.2 g. 6-nitro-3-indolecarboxaldehyde (II), m. 302-4° (Me₂CO-EtOH). A solution of 5.7 g. KNO₃ in 10 ml. H₂SO₄ was added slowly at 10° to 5 g. I in 15 ml. concentrated H₂SO₄, the mixture stirred 10 min., poured onto ice, and the precipitate extracted with 100 ml. boiling C₆H₆ to yield 5.5 g. mixture, which was shown by spectrophotometric analysis to consist of 34% II and 66% 5-nitro-3-indolecarboxaldehyde (III), m. 300-2°; fractional crystallization from EtOH allowed partial separation of the two compounds A solution of 0.35 g. II in 10 ml. EtOH and 1 ml. 2N NaOH was boiled 15 min. with 0.25 g. KBH₄, cooled, acidified, and extracted with Et₂O; the residue of the evaporation of the Et₂O was extracted with ligroine to give 5 mg. yellow needles (6-nitroskatole ?), m. 122-4°; the ligroineinsol. part yielded after extraction with C₆H₆ 25 mg. 3-hydroxymethyl-6-nitroindole (IV), m. 144-6° (decomposition). Oxidation of 0.2 g. II in 1 ml. 2N NaOH by refluxing 1 hr. with 0.54 g. AgNO₃ in 10 ml. 2N NH₃ gave 60 mg. 6-nitro-3-indolecarboxylic acid (V), m. 265-7°; the same result was obtained with alk. KMnO₄; similarly the mixture of II and III gave a mixture, m. 225-30°, of V and 5-nitro-3-indolecarboxylic acid (VI). V and VI were transformed resp. into 6- and 5-nitroindole by heating at 160-80° in quinoline. A suspension of 1 g. ethyl 3-indoleglyoxylate (VII) in 8 ml. AcOH heated 30 min. at 80° with 0.8 ml. HNO₃ (d. 1.37) gave 0.4 g. ethyl 6-nitro-3-indolecarboxylate (VIII), m. 284-6° (decomposition) (EtOH), while 0.11 g. 4-nitro-3-indoleglyoxylate, m. 184-6° (EtOH), was obtained by concentration of the mother liquor. Nitration of 4 g. VII in 28 ml. concentrated H₂SO₄ with 2.8 g. KNO₃ led to 3.3 g. mixture of 34% VIII and 66% ethyl 5-nitro-3-indoleglyoxylate (IX), m. 280-2° (decomposition), which was separated in part by crystallization from Me₂CO. Saponification of VIII with KOH in EtOH gave the free acid (X), decomposing above 250° (Me₂NCHO-H₂O); similarly, IX yielded 5-nitro-3-indolecarboxylic acid (XI), decomposing at 233° (Me₂NCHO-H₂O). X and XI were decarboxylated to II and III at 170-80° in quinoline. Ultraviolet curves were given for I, II, III, IV, VIII, and IX.

Gazzetta Chimica Italiana published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, HPLC of Formula: 10242-03-2.

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

Cherubini, Fabio published the artcileSrc inhibitors modulate frataxin protein levels, Product Details of C19H21N3O3S, the publication is Human Molecular Genetics (2015), 24(15), 4296-4305, database is CAplus and MEDLINE.

Defective expression of frataxin is responsible for the inherited, progressive degenerative disease Friedreich’s Ataxia (FRDA). There is currently no effective approved treatment for FRDA and patients die prematurely. Defective frataxin expression causes critical metabolic changes, including redox imbalance and ATP deficiency. As these alterations are known to regulate the tyrosine kinase Src, we investigated whether Src might in turn affect frataxin expression. We found that frataxin can be phosphorylated by Src. Phosphorylation occurs primarily on Y118 and promotes frataxin ubiquitination, a signal for degradation Accordingly, Src inhibitors induce accumulation of frataxin but are ineffective on a non-phosphorylatable frataxin-Y118F mutant. Importantly, all the Src inhibitors tested, some of them already in the clinic, increase frataxin expression and rescue the aconitase defect in frataxin-deficient cells derived from FRDA patients. Thus, Src inhibitors emerge as a new class of drugs able to promote frataxin accumulation, suggesting their possible use as therapeutics in FRDA.

Human Molecular Genetics 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

Lian, Xiaojun published the artcileA small molecule inhibitor of Src family kinases promotes simple epithelial differentiation of human pluripotent stem cells, Category: indole-building-block, the publication is PLoS One (2013), 8(3), e60016, database is CAplus and MEDLINE.

Human pluripotent stem cells (hPSCs) provide unprecedented opportunities to study the earliest stages of human development in vitro and have the potential to provide unlimited new sources of cells for regenerative medicine. Although previous studies have reported cytokeratin 14+/p63+ keratinocyte generation from hPSCs, the multipotent progenitors of epithelial lineages have not been described and the developmental pathways regulating epithelial commitment remain largely unknown. Here we report membrane localization of β-catenin during retinoic acid (RA) – induced epithelial differentiation. In addition hPSC treatment with the Src family kinase inhibitor SU6656 modulated β-catenin localization and produced an enriched population of simple epithelial cells under defined culture conditions. SU6656 strongly upregulated expression of cytokeratins 18 and 8 (K18/K8), which are expressed in simple epithelial cells, while repressing expression of the pluripotency gene Oct4. This homogeneous population of K18+K8+Oct4- simple epithelial precursor cells can further differentiate into cells expressing keratinocyte or corneal-specific markers. These enriched hPSC-derived simple epithelial cells may provide a ready source for development and toxicol. cell models and may serve as a progenitor for epithelial cell transplantation applications.

PLoS One 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, 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