Month: November 2022

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

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