Month: December 2022

Jiang, B. published the artcileA highly stereoselective synthesis of indolyl N-substituted glycines, Recommanded Product: (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Tetrahedron Letters (2001), 42(13), 2545-2547, database is CAplus.

Optically active N-substituted α-indolylglycines were synthesized with high diastereoselectivity by Mannich reaction of an indolylboronic acid with glyoxylic acid using (R)-α-methylbenzylamine as the chiral auxiliary. The absolute configuration of one of the products was determined by a single-crystal x-ray anal.

Tetrahedron 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, Recommanded Product: (1-tosyl-1H-Indol-3-yl)boronic acid.

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

Jiang, B. published the artcileSynthesis and cytotoxicity evaluation of novel indolylpyrimidines and indolylpyrazines as potential antitumor agents, Computed Properties of 149108-61-2, the publication is Bioorganic & Medicinal Chemistry (2001), 9(5), 1149-1154, database is CAplus and MEDLINE.

Novel indolylpyrimidines and indolylpyrazines have been synthesized as potential antitumor agents. They were screened in a panel of 60 human tumor cell lines in vitro. Several compounds exhibited efficiently cytotoxic activities with GI₅₀ values in the low micromolar range against a variety of human cancer cell lines. 2,4-Bis(3′-indolyl)pyrimidine displayed selective cytotoxic activity against IGROV1 tumor cell line with the GI₅₀ value below 0.01 μM.

Bioorganic & Medicinal 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, Computed Properties 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

Wan, Shanhe published the artcileInsight into binding mechanisms of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations, Quality Control of 1942114-09-1, the publication is Journal of Biomolecular Structure and Dynamics (2019), 37(16), 4384-4394, database is CAplus and MEDLINE.

Lung cancer is the leading cause of cancer death, and epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small-cell lung cancer (NSCLC), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the EGFR inhibitors Gefitinib and Erlotinib initially, but soon develop resistance to them due to the emergence of the gatekeeper mutation T790M. The new-generation inhibitors such as AZD9291, HM61713, CO-1686 and WZ4002 can overcome T790M through covalent binding to Cys 797, but ultimately lose their efficacy upon the emergence of the C797S mutation that abolishes the covalent bonding. Allosteric inhibitors EAI001 and EAI045 are a new type of EGFR inhibitors that bind to EGFR away from the ATP-binding site and not relying on Cys 797. In this study, mol. dynamics simulations and free energy calculations were carried out on EAI001 and EAI045 in complex with EGFR, revealing the detailed inhibitory mechanism of EAI001 and EAI045 as EGFR allosteric inhibitor, which was expected to provide a basis for rational drug design of the EGFR allosteric inhibitors.

Journal of Biomolecular Structure and Dynamics 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 C15H14Cl2S2, 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

Dufour, Marine published the artcileMechanism-Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is ChemBioChem (2011), 12(8), 1203-1208, database is CAplus and MEDLINE.

A role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism-based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochem. studies confirmed the mechanism-based inhibition, whereas x-ray crystallog. and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.

ChemBioChem 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 C18H16N2O6, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione.

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

Han, Xiaoming published the artcileMonitoring protein kinase activity in cell lysates using a high-density peptide microarray, Synthetic Route of 330161-87-0, the publication is Journal of Biomolecular Screening (2009), 14(3), 256-262, database is CAplus and MEDLINE.

Monitoring and targeting protein kinases is widely accepted as a promising approach for disease diagnosis and drug discovery. For this purpose, the authors have developed an original type of peptide array as a high-throughput screening assay for quant. evaluating kinase activity. A volume of 2 nL of peptide solution was spotted onto a formyl group-modified glass slide by using an arrayer, which was designed for use with protein chip technol. The phosphorylation was recognized by fluorescence-label antibody and detected with an automatic microarray scanner widely used in DNA chip technol. The system needs low sample volume, provides a high-d. peptide array, and supplies high reproducibility. It provided enough sensitivity for inhibitor screening, even though a relatively low concentration of purified kinase was employed. The assay also proved useful for the detection of intracellular kinase activity as well as for the measurement of the fluctuations of intracellular protein kinase activity with drug stimulation. Thus, this peptide array would be applicable for kinase-targeted diagnosis, cell-based drug screening, and signal pathway investigation.

Journal of Biomolecular Screening 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

Nemoto, Tetsuhiro published the artcileCatalytic Asymmetric Total Synthesis of Tangutorine, HPLC of Formula: 167015-84-1, the publication is Organic Letters (2010), 12(4), 872-875, database is CAplus and MEDLINE.

The first enantioselective total synthesis of (-)-tangutorine (I) was achieved via a Pd-catalyzed asym. allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand as the key step.

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 C15H20N2O2, HPLC of Formula: 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

Kuki, Kazumasa published the artcileEnhancement of TGF-β-induced Smad3 activity by c-Abl-mediated tyrosine phosphorylation of its coactivator SKI-interacting protein (SKIP), SDS of cas: 330161-87-0, the publication is Biochemical and Biophysical Research Communications (2017), 490(3), 1045-1051, database is CAplus and MEDLINE.

A review. C-Abl is a non-receptor-type tyrosine kinase that plays an important role in cell proliferation, migration, apoptosis, and fibrosis. Furthermore, although c-Abl is involved in transforming growth factor-β (TGF-β) signaling, its mol. functions in TGF-β signaling are not fully understood. Here, we found that c-Abl phosphorylates SKI-interacting protein (SKIP), a nuclear cofactor of the transcription factor Smad3. The c-Abl inhibitor imatinib suppressed TGF-β-induced expression of Smad3 targets as well as SKIP/Smad3 interaction. TGF-β-stimulation induced tyrosine phosphorylation of SKIP, and this phosphorylation was suppressed by imatinib. Tyr²⁹², Tyr⁴³⁰, and Tyr⁴³³ residues in SKIP were shown to be involved in c-Abl-mediated phosphorylation. Phosphomimetic glutamic acid substitution at Tyr²⁹² in SKIP enhanced, whereas its phospho-dead phenylalanine substitution attenuated TGF-β-induced SKIP/Smad3 interaction. Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3. Taken together, these results suggest that c-Abl phosphorylates SKIP mainly at Tyr²⁹² and promotes SKIP/Smad3 interaction for the full activation of TGF-β/Smad3 signaling.

Biochemical and Biophysical Research 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, SDS of cas: 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

Hu, Xianglong published the artcile2-Oxo-3,4-dihydropyrimido[4, 5-d] pyrimidines as new reversible inhibitors of EGFR C797S (Cys797 to Ser797) mutant, Formula: C19H14FN3O3S, the publication is Chinese Chemical Letters (2020), 31(5), 1281-1287, database is CAplus.

Extensive structure-activity relationships (SARs) study of JND3229 was conducted to yield a series of new reversible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFR^C797S inhibitors. One of the most potent compound 6i potently suppressed EGFR^{L858R/T790M/C797S} kinase with an IC₅₀ value of 3.1 nmol/L, and inhibited the proliferation of BaF3 cells harboring EGFR^{L858R/T790M/C797S} and EGFR^{19D/T790M/C797S} mutants with IC₅₀ values of 290 nmol/L and 316 nmol/L, resp. Further, 6i dose-dependently induced suppression of the phosphorylation of EGFR^{L858R/T790M/C797S} and EGFR^{19D/T790M/C797S} in BaF3 cells. Compound 6i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients.

Chinese Chemical Letters 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, Formula: C19H14FN3O3S.

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

Bremer, Paul T. published the artcilePicolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain, Formula: C14H17BFNO2, the publication is Chemical Communications (Cambridge, United Kingdom) (2016), 52(84), 12521-12524, database is CAplus and MEDLINE.

In developing small-mol. inhibitors of botulinum neurotoxin serotype A light chain (BoNT/A LC), substituted picolinic acids were identified. Extensive investigation into the SAR of the picolinic acid scaffold revealed 5-(1-butyl-4-chloro-1H-indol-2-yl)picolinic acid (I), which possessed low micromolar activity against BoNT/A. Kinetic and docking studies demonstrated binding of I to the β-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.

Chemical Communications (Cambridge, United Kingdom) published new progress about 1256359-96-2. 1256359-96-2 belongs to indole-building-block, auxiliary class Indole,Fluoride,Boronic acid and ester,Boronic Acids,Boronate Esters,Boronate Esters, name is 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H17BFNO2, Formula: C14H17BFNO2.

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

Bremer, Paul T. published the artcilePicolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain, Quality Control of 1256358-95-8, the publication is Chemical Communications (Cambridge, United Kingdom) (2016), 52(84), 12521-12524, database is CAplus and MEDLINE.

In developing small-mol. inhibitors of botulinum neurotoxin serotype A light chain (BoNT/A LC), substituted picolinic acids were identified. Extensive investigation into the SAR of the picolinic acid scaffold revealed 5-(1-butyl-4-chloro-1H-indol-2-yl)picolinic acid (I), which possessed low micromolar activity against BoNT/A. Kinetic and docking studies demonstrated binding of I to the β-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.

Chemical Communications (Cambridge, United Kingdom) published new progress about 1256358-95-8. 1256358-95-8 belongs to indole-building-block, auxiliary class Indole,Chloride,Boronic acid and ester,Boronic Acids,Boronate Esters, name is 4-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H17BClNO2, Quality Control of 1256358-95-8.

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