Indole Building Blocks

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

Liu, Xiu-Fen published the artcileAntitumor Effects of Immunotoxins Are Enhanced by Lowering HCK or Treatment with Src Kinase Inhibitors, Product Details of C19H21N3O3S, the publication is Molecular Cancer Therapeutics (2014), 13(1), 82-89, database is CAplus and MEDLINE.

Recombinant immunotoxins (RIT) are agents being developed for cancer treatment. They are composed of an Fv that binds to a cancer cell, fused to a 38-kDa fragment of Pseudomonas exotoxin A. SS1P is a RIT that targets mesothelin, a protein expressed on mesothelioma as well as pancreatic, ovarian, lung, and other cancers. Because the protein tyrosine kinase family regulates a variety of cellular processes and pathways, we hypothesized that tyrosine kinases might regulate susceptibility to immunotoxin killing. To investigate their role, we used siRNAs to lower the level of expression of the 88 known tyrosine kinases. We identified five tyrosine kinases, INSR, HCK, SRC, PDGFRβ, and BMX that enhance the activity of SS1P when their level of expression is lowered by siRNAs. We further investigated the Src family member HCK in this study. Knocking down of SRC slightly increased SS1P killing in A431/H9 cells, but knocking down HCK substantially enhanced killing by SS1P. We investigated the mechanism of enhancement and found that HCK knockdown enhanced SS1P cleavage by furin and lowered levels of Mcl-1 and raised Bax. We then found that Src inhibitors mimic the stimulatory effect of HCK knockdown; both SU6656 and SKI-606 (bosutinib) enhanced immunotoxin killing of mesothelin-expressing cells by SS1P and CD22-expressing cells by HA22 (moxetumomab pasudotox). SU6656 also enhanced the antitumor effects of SS1P and HA22 in mouse xenograft tumor models. Our data suggest that the combination of immunotoxin with tyrosine kinase inhibitors may be an effective way to treat some cancers. Mol Cancer Ther; 13(1); 82-89. ©2013 AACR.

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

Friedman, Adam A. published the artcileFeasibility of Ultra-High-Throughput Functional Screening of Melanoma Biopsies for Discovery of Novel Cancer Drug Combinations, Recommanded Product: SU6656, the publication is Clinical Cancer Research (2017), 23(16), 4680-4692, database is CAplus and MEDLINE.

Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclin. models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool. Exptl. Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of thousands of drug combinations in a patient-specific manner within days of biopsy. In parallel, patient-derived xenograft (PDX) mouse models were created and novel combinations tested for their ability to shrink matched PDXs. Results: The screening method identifies specific drug combinations in tumor cells with patterns that are distinct from those obtained from stable cell lines. Screening results were highly specific to individual patients. For patients with matched PDX models, we confirmed that individualized novel targeted therapy combinations could inhibit tumor growth. In particular, a combination of multi-kinase and PI3K/Akt inhibitors was effective in some BRAF-wild-type melanomas, and the addition of cediranib to the BRAF inhibitor PLX4720 was effective in a PDX model with BRAF mutation. Conclusions: This proof-of-concept study demonstrates the feasibility of using primary biopsies directly for combinatorial drug discovery, complementing stable cell lines and xenografts, but with much greater speed and efficiency. This process could potentially be used in a clin. setting to rapidly identify therapeutic strategies for individual patients. Clin Cancer Res; 23(16); 4680-92. ©2017 AACR.

Clinical Cancer Research 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

Wu, Cheng-Jun published the artcileDesign, synthesis and biological evaluation of indole-based [1,2,4]triazolo[4,3-a] pyridine derivatives as novel microtubule polymerization inhibitors, Application of 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is European Journal of Medicinal Chemistry (2021), 113629, database is CAplus and MEDLINE.

A series of indole-based [1,2,4]triazolo [4,3-a]pyridine derivatives was designed and synthesized as novel microtubulin polymerization inhibitors by using a conformational restriction strategy. These compounds exhibited moderate to potent anti-proliferative activities against a panel of cancer cell lines (HeLa, A549, MCF-7 and HCT116). Among them, compound I featuring a N-methyl-5-indolyl substituent at the C-6 position of the [1,2,4]triazolo [4,3-a]pyridine core exhibited the highest antiproliferative activity with the IC₅₀ values ranging from 15 to 69 nM, and remarkable inhibitory effect on tubulin polymerization with an IC₅₀ value of 1.64μM. Mechanistic studies revealed that compound I induced cellular apoptosis and cell cycle arrest at the G₂/M phase in a dose-dependent fashion. Moreover, compound I significantly suppressed wound closure and disturbed microtubule networks.

European Journal of Medicinal 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 C14H10O4, Application 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

Wang, Cong-Shuai published the artcileDesign of C3-Alkenyl-Substituted 2-Indolylmethanols for Catalytic Asymmetric Interrupted Nazarov-Type Cyclization, HPLC of Formula: 100123-25-9, the publication is Advanced Synthesis & Catalysis (2018), 360(5), 846-851, database is CAplus.

The C3-alkenyl-substituted 2-indolylmethanols were designed as a new class of substrates for catalytic asym. interrupted Nazarov-type cyclizations. In the presence of a chiral phosphoric acid as a mild chiral Bronsted acid, the interrupted Nazarov-type cyclization of C3-alkenyl-substituted 2-indolylmethanols I (R¹ = Ph, 4-ClC₆H₄, 2-FC₆H₄, etc.; R² = Ph, 3-FC₆H₄, 3-MeC₆H₄; R³ = H, Cl, Br, MeO) with nucleophiles R⁴H (R⁴ = 3-indolyl, 2-hydroxy-1-naphthyl, etc.) occurred smoothly to construct cyclopenta[b]indole frameworks II with generally excellent diastereo- and enantioselectivities (up to >95:5 dr, >99% ee).

Advanced Synthesis & Catalysis published new progress about 100123-25-9. 100123-25-9 belongs to indole-building-block, auxiliary class Indole,Bromide,Ester,Aldehyde, name is Ethyl 5-bromo-3-formyl-1H-indole-2-carboxylate, and the molecular formula is C6H5F4NO3S, HPLC of Formula: 100123-25-9.

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