Day: November 21, 2022

Lo, Wei Fun published the artcileA highly selective Ir-catalyzed borylation of 2-substituted indoles: a new access to 2,7- and 2,4,7-substituted indoles, Name: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Tetrahedron Letters (2007), 48(3), 371-375, database is CAplus.

The selective CH-functionalization of 2-substituted indoles was presented. Using bis(pinacolato)diboron in the presence of iridium complexes, a novel catalytic mono-borylation was observed preferentially at the 7-position of the indole. This allowed for an efficient synthesis of various 2,7-di- and 2,4,7-trisubstituted indoles, e.g., I (R = Me, Ph or CO₂Et), which are otherwise difficult to access. The scope and limitation of the method was demonstrated.

Tetrahedron Letters 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, Name: 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

Arang, Nadia published the artcileIdentifying host regulators and inhibitors of liver stage malaria infection using kinase activity profiles, Recommanded Product: SU6656, the publication is Nature Communications (2017), 8(1), 1-9, database is CAplus and MEDLINE.

Plasmodium parasites have extensive needs from their host hepatocytes during the obligate liver stage of infection, yet there remains sparse knowledge of specific host regulators. Here we assess 34 host-targeted kinase inhibitors for their capacity to eliminate Plasmodium yoelii-infected hepatocytes. Using pre-existing activity profiles of each inhibitor, we generate a predictive computational model that identifies host kinases, which facilitate Plasmodium yoelii liver stage infection. We predict 47 kinases, including novel and previously described kinases that impact infection. The impact of a subset of kinases is exptl. validated, including Receptor Tyrosine Kinases, members of the MAP Kinase cascade, and WEE1. Our approach also predicts host-targeted kinase inhibitors of infection, including compounds already used in humans. Three of these compounds, VX-680, Roscovitine and Sunitinib, each eliminate >85% of infection. Our approach is well-suited to uncover key host determinants of infection in difficult model systems, including field-isolated parasites and/or emerging pathogens.

Nature Communications 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

Neel, David A. published the artcileSynthesis of bisindolylmaleimides using a palladium catalyzed cross-coupling reaction, Synthetic Route of 149108-61-2, the publication is Bioorganic & Medicinal Chemistry Letters (1998), 8(1), 47-50, database is CAplus and MEDLINE.

Bis(indolyl)maleimides are known to be potent and selective PKC inhibitors. A new synthesis of this class of compound is reported. One of the target compounds was 3-(1H-indol-3-yl)-1-methyl-4-(1-methyl-1H-indol-3-yl)-1H-Pyrrole-2,5-dione. The key step is a Suzuki cross-coupling reaction using a readily available indolylmaleimide triflate intermediate.

Bioorganic & Medicinal Chemistry Letters 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, Synthetic Route of 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

Qiu, Di published the artcileSynthesis of Pinacol Arylboronates from Aromatic Amines: A Metal-Free Transformation, Safety of 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of Organic Chemistry (2013), 78(5), 1923-1933, database is CAplus and MEDLINE.

A metal-free borylation process based on Sandmeyer-type transformation using arylamines derivatives as the substrates was developed. Through optimization of the reaction conditions, this novel conversion can be successfully applied to a wide range of aromatic amines, affording borylation products in moderate to good yields. Various functionalized arylboronates, which are difficult to access by other methods, can be easily obtained with this metal-free transformation. Also, this transformation can be followed by Suzuki-Miyaura cross-coupling without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction mechanism involving radical species is proposed.

Journal of Organic Chemistry 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, Safety of 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

Zhao, Yan published the artcileRevisiting the molecular mechanism of acquired resistance to reversible tyrosine kinase inhibitors caused by EGFR gatekeeper T790M mutation in non-small-cell lung cancer, Related Products of indole-building-block, the publication is Medicinal Chemistry Research (2018), 27(9), 2160-2170, database is CAplus.

A variety of tyrosine kinase inhibitors (TKIs) have been developed to target human epidermal growth factor receptor (EGFR) for non-small-cell lung cancer (NSCLC) therapy. However, many patients treated with first-line TKIs are clin. observed to eventually establish a gatekeeper T790M mutation in EGFR active site, which plays a primary role in development of acquired resistance to TKIs. Here, we attempted to investigate the intermol. interactions of wild-type EGFR (EGFRWT) and its T790M mutant (EGFRT790M) with a number of culled reversible EGFR TKIs, paying attention to the structural and energetic response of inhibitor ligands to the mutation. A TKI panel consisting of 9 sophisticated EGFR inhibitors was manually culled, and an integration of structural modeling, virtual mutagenesis, quantum mechanics/mol. mechanics anal. and binding assay was performed to systematically examine the binding of these inhibitors to both wild-type and mutant EGFR. T790M-introduced steric hindrance plays a primary role in the acquired resistance to WT-selective inhibitors, whereas the mutation is observed to form addnl. noncovalent forces with WT-sparing inhibitors. Structural anal. reveals that the steric hindrance generally induces a conformational change of WT-selective inhibitors in EGFR active site, while the weak noncovalent forces have only a moderate effect on the binding mode of WT-sparing inhibitors. EAI045, the first fourth-generation EGFR inhibitor, exhibits a moderate affinity to EGFR and possesses an exquisite selectivity for wild type over mutant kinase (�-fold). This is expected if considering that the EAI045 is an allosteric inhibitor, which does not need to directly compete with ATP, and high affinity and selectivity are therefore not required for the inhibitor.

Medicinal Chemistry Research 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 C9H9BN2O3, 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

Zhang, Li published the artcileVisible-Light-Induced Organocatalytic Borylation of Aryl Chlorides, Synthetic Route of 642494-36-8, the publication is Journal of the American Chemical Society, database is CAplus and MEDLINE.

The preparation of arylboronates from unactivated aryl chlorides in a transition-metal-free manner is rather challenging. There are only few examples to achieve this goal by using UV irradiation Based on the mechanistic understanding of the diboron/methoxide/pyridine reaction system, we achieved photoactivation of the in situ generated super electron donor and developed a visible-light-induced organocatalytic method for efficient borylation of unactivated aryl chlorides.

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 C14H10N2O, Synthetic Route of 642494-36-8.

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

Zhang, Li published the artcileVisible-Light-Induced Organocatalytic Borylation of Aryl Chlorides, Safety of 1-Benzyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society, database is CAplus and MEDLINE.

The preparation of arylboronates from unactivated aryl chlorides in a transition-metal-free manner is rather challenging. There are only few examples to achieve this goal by using UV irradiation Based on the mechanistic understanding of the diboron/methoxide/pyridine reaction system, we achieved photoactivation of the in situ generated super electron donor and developed a visible-light-induced organocatalytic method for efficient borylation of unactivated aryl chlorides.

Journal of the American Chemical Society published new progress about 1206163-56-5. 1206163-56-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Benzene,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 1-Benzyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole, and the molecular formula is C8H19NO, Safety of 1-Benzyl-5-(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, Kun published the artcileEnantioselective Bromocyclization of Tryptamines Induced by Chiral Co(III)-Complex-Templated Bronsted Acids under an Air Atmosphere, Product Details of C15H20N2O2, the publication is Journal of Organic Chemistry (2018), 83(12), 6815-6823, database is CAplus and MEDLINE.

The chiral Co(III)-complex-templated Bronsted acids were found to be efficient bifunctional phase-transfer catalysts for the highly enantioselective bromocyclization of protected tryptamines with readily available N-bromosuccinimide (NBS) under an air atm. The 3-bromohexahydropyrrolo[2,3-b]indoles, which are key building blocks of cyclotryptamine alkaloids, were thus obtained in up to 95% yield and 93.5:6.5 er.

Journal of Organic Chemistry 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 C15H20N2O2, Product Details of C15H20N2O2.

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

Xie, Weiqing published the artcileHighly Enantioselective Bromocyclization of Tryptamines and Its Application in the Synthesis of (-)-Chimonanthine, Application In Synthesis of 167015-84-1, the publication is Angewandte Chemie, International Edition (2013), 52(49), 12924-12927, database is CAplus and MEDLINE.

The authors report the first highly enantioselective bromocyclization of tryptamines and its application to the enantioselective synthesis of (-)-chimonanthine (I). For example, tryptamine II reacted with bromine salt III in the presence of phosphoric acid ligand IV and NaHCO₃ to give pyrrolo[2,3-b]indoledicarboxylate V in quant. yield and 96% ee.

Angewandte Chemie, International Edition 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 C13H19Br2ClN2O, Application In Synthesis 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

Yu, Ah-Ran published the artcileAlpha-naphthoflavone induces apoptosis through endoplasmic reticulum stress via c-Src-, ROS-, MAPKs-, and arylhydrocarbon receptor-dependent pathways in HT22 hippocampal neuronal cells, Quality Control of 330161-87-0, the publication is NeuroToxicology (2019), 39-51, database is CAplus and MEDLINE.

α-Naphthoflavone (αNF) is a prototype flavone, also known as a modulator of aryl hydrocarbon receptor (AhR). In the present study, we investigated the mol. mechanisms of αNF-induced cytotoxic effects in HT22 mouse hippocampal neuronal cells. αNF induced apoptotic cell death via activation of caspase-12 and -3 and increased expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by treatment with the ER stress inhibitor, salubrinal, or by CHOP siRNA transfection reduced αNF-induced cell death. αNF activated mitogen-activated protein kinases (MAPKs), such as p38, JNK, and ERK, and inhibition of MAPKs reduced αNF-induced CHOP expression and cell death. αNF also induced accumulation of reactive oxygen species (ROS) and an antioxidant, N-acetylcysteine, reduced αNF-induced MAPK phosphorylation, CHOP expression, and cell death. Furthermore, αNF activated c-Src kinase, and inhibition of c-Src by a kinase inhibitor, SU6656, or siRNA transfection reduced αNF-induced ROS accumulation, MAPK activation, CHOP expression, and cell death. Inhibition of AhR by an AhR antagonist, CH223191, and siRNA transfection of AhR and AhR nuclear translocator reduced αNF-induced AhR-responsive luciferase activity, CHOP expression, and cell death. Finally, we found that inhibition of c-Src and MAPKs reduced αNF-induced transcriptional activity of AhR. Taken together, these findings suggest that αNF induces apoptosis through ER stress via c-Src-, ROS-, MAPKs-, and AhR-dependent pathways in HT22 cells.

NeuroToxicology 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 C15H20BNO5, 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