Month: December 2022

Bremer, Paul T. published the artcilePicolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain, Name: 5-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, 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 1256358-91-4. 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, Name: 5-Chloro-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

Bremer, Paul T. published the artcilePicolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain, Product Details of C15H20BNO2, 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 1072811-23-4. 1072811-23-4 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Boronic Acids,Boronate Esters, name is 4-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO2, Product Details of C15H20BNO2.

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

Chu, Zixuan published the artcileDevelopment and Validation of an LC-MS/MS Method for Quantitative Determination of EAI045, A Novel EGFR Inhibitor, in Rat Plasma, Category: indole-building-block, the publication is Current Pharmaceutical Analysis (2020), 16(3), 273-279, database is CAplus.

EAI045 is the fourth-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), which can overcome acquired resistance to the third-generation EGFR TKIs and is the first allosteric inhibitor that targets T790M and C797S EGFR mutants. A rapid and sensitive LC-MS/MS method was established and validated for the quantification of EAI045 in rat plasma. Chromatog. separation was carried out at 25°C on a Hypersil GOLD C18 column (50 mm x 2.1 mm, 3μm) and eluted on a gradient mobile phase of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.5 mL/min. The mass spectrometer was operated in the pos. ESI mode and selected reaction monitoring mode. The assay was validated over a concentration range of 1.0 – 1000 ng/mL for EAI045 with a lower limit of quantification (LLOQ) of 1.0 ng/mL. The intra- and inter-batch accuracy for the EAI045 ranged from 92.25% to 97.18% and 95.94% to 102.69%, and the intra- and inter-batch precision for the EAI045 ranged from 1.41% to 4.57% and 5.18% to 6.37%, resp. The extraction recovery, matrix effect and stability met all requirements of the guidelines for bioanal. method validation. The rapid and sensitive LC-MS/MS method was successfully applied in a pharmacokinetic study of EAI045 following oral administration (5 mg/kg) to rats.

Current Pharmaceutical Analysis 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, 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

Gao, Hongyin published the artcileRapid Synthesis of Fused N-Heterocycles by Transition-Metal-Free Electrophilic Amination of Arene C-H Bonds, Application of (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Angewandte Chemie, International Edition (2014), 53(10), 2701-2705, database is CAplus and MEDLINE.

We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations

Angewandte Chemie, International Edition 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, Application of (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

Gao, Yuning published the artcileEnantioselective Synthesis of Polycyclic Indole Derivatives Based on aza-Morita-Baylis-Hillman Reaction, HPLC of Formula: 220943-23-7, the publication is ACS Catalysis (2015), 5(11), 6608-6614, database is CAplus.

A chiral phosphine-catalyzed asym. aza-Morita-Baylis-Hillman reaction between indole-derived sulfonyl imines and bis(3-chlorophenyl)methyl acrylate has been developed, giving the desired adducts in good yields and enantiomeric excess values along with the further transformations to polycyclic indoles such as dihydropyrido[1,2-a]indole and dihydropyrazino[1,2-a]indole skeleton.

ACS Catalysis 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, HPLC of Formula: 220943-23-7.

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

Zhang, Jitan published the artcilePd(II)-Catalyzed enantioconvergent twofold C-H annulation to access atropisomeric aldehydes: a platform for diversity-oriented-synthesis, Computed Properties of 220943-23-7, the publication is Organic Chemistry Frontiers (2021), 8(13), 3404-3412, database is CAplus.

Herein, the first Pd(II)-catalyzed atroposelective dual C-H annulative strategy for the assembly of axially chiral aldehyde frameworks such as I [R = Me, Et, i-Pr] using com. available amino acid as the transient auxiliary and chiral pool was presented. This reaction accommodated a broad substrate scope to give atropisomeric aldehydes bearing both C-C and N-C chiral axes in good yields (up to 95%) with excellent enantioinduction (up to 99%). The utility of this synthetic methodol. was testified by various practical late-stage transformations, thereby accomplishing diversity-oriented synthesis of structurally diverse biaryl atropisomers and several functionalized axially chiral species such as bifunctional organocatalysts. Moreover, a series of mechanistic studies had provided more details for this catalytic transformation.

Organic Chemistry Frontiers 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 C20H17FO4S, Computed Properties of 220943-23-7.

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

Wang, Guanghui published the artcileDouble N,B-Type Bidentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C-H Borylation, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society (2015), 137(25), 8058-8061, database is CAplus and MEDLINE.

Boryl ligands hold promise in catalysis due to their very high electron-donating property. In this communication double N,B-type boryl anions were designed as bidentate ligands to promote an sp² C-H borylation reaction. A sym. pyridine-containing tetraaminodiborane(4) compound was readily prepared as the ligand precursor that could be used, in combination with [Ir(OMe)(COD)]₂, to in situ generate a highly active catalyst for a broad range of (hetero)arene substrates including highly electron-rich and/or sterically hindered ones. This work provides the 1st example of a bidentate boryl ligand in supporting homogeneous organometallic catalysis.

Journal of the American Chemical Society 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 C5H6BNO2, Recommanded Product: 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

Li, Yueshan published the artcileIdentification of 5-(2,3-Dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as a new class of receptor-interacting protein kinase 1 (RIPK1) inhibitors, which showed potent activity in a tumor metastasis model, Category: indole-building-block, the publication is Journal of Medicinal Chemistry (2018), 61(24), 11398-11414, database is CAplus and MEDLINE.

We herein report the structural optimization and structure-activity relationship studies of 5-(2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as a new class of receptor-interacting protein kinase 1 (RIPK1) inhibitors. Among all obtained RIPK1 inhibitors, I is the most active one. This compound potently inhibited RIPK1 with a binding affinity (K_D) of 0.004μM and an enzymic IC₅₀ value of 0.011μM and also showed good kinase selectivity. It could efficiently protect cells from necroptosis and attenuate the necrotic cell death of vascular endothelial cells induced by tumor cells both in vitro and in vivo. Importantly, I exhibited excellent antimetastasis activity in the exptl. B16 melanoma lung metastasis model. It also displayed favorable pharmacokinetic properties. Collectively, I could be a promising agent for preventing tumor metastasis.

Journal of Medicinal 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 C19H28BNO4, 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

Jiang, B. published the artcileSynthesis and antitumor evaluation of novel monoindolyl-4-trifluoromethylpyridines and bisindolyl-4-trifluoromethylpyridines, Related Products of indole-building-block, the publication is Bioorganic & Medicinal Chemistry Letters (2001), 11(4), 475-477, database is CAplus and MEDLINE.

A series of novel monoindolyl-4-trifluoromethylpyridines and bisindolyl-4-trifluoromethylpyridines was designed and synthesized as potential antitumor agents. They were evaluated for preliminary cytotoxic activity against P388 and A-549 cells with IC₅₀ values. 4-Trifluoromethyl-2,6-bis[3′-(N-tosyl-6′-methoxyl-indolyl)] pyridine was identified as the most potent in this series.

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, 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

Ma, Yan-rong published the artcileAn LC-MS/MS analytical method for the determination of uremic toxins in patients with end-stage renal disease, Synthetic Route of 2642-37-7, the publication is Journal of Pharmaceutical and Biomedical Analysis (2020), 113551, database is CAplus and MEDLINE.

End-stage renal disease (ESRD) is the last stage of chronic kidney disease, characterized by the progressive accumulation of uremic toxins (UTs). Hemodialysis is the standard approach to remove UTs from the body. Creatinine and urea levels are important indexes of hemodialysis effectiveness, but the utility of those markers to estimate the removal of UTs, especially protein-binding UTs is limited. We developed an LC-MS/MS method for the quantification of UTs and to provide markers for evaluating hemodialysis effectiveness. These substances were extracted from serum samples after acetonitrile precipitation of protein and then separated on a HILIC column. The flow rate was 0.6 mL/min with a run time of 8.0 min for the neg. ion mode and pos. ion mode each. In this study 26 UTs were determined in normal subjects and in patients with ESRD before and after hemodialysis; serum levels were significantly higher in patients with ESRD than in subjects with normal renal function. A significant decrease in a variety of serum UTs were observed in patients after dialysis treatment, but no change in the levels of orotic acid, CMPF, kynurenic acid, p-cresol sulfate, phenyl-β-D-glucuronide, 4-ethylphenyl sulfate and 3-indolyl-β-D-glucopyranoside was found. These results show that some UTs could not be completely removed by hemodialysis. In addition, some biomarkers of different types of UTs are proposed for evaluating hemodialysis effectiveness.

Journal of Pharmaceutical and Biomedical Analysis 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, Synthetic Route of 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