Category: indole-building-block

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

Wu, Xiuli published the artcileValidated LC method for the enantiomeric separation of EAI045 on chiral stationary phase, Product Details of C19H14FN3O3S, the publication is Journal of Chromatographic Science (2020), 58(6), 562-568, database is CAplus and MEDLINE.

A simple and accurate chiral liquid chromatog. method was developed for enantiomeric resolution and determination of 2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide (EAI045). The enantiomers of EAI045 were baseline resolved on a Chiralpak AD-H (250 mm x 4.6 mm, 5μm) column using a mobile phase system containing n-hexane: 2-propanol (75: 25 volume/volume) at a flow rate of 1 mL min-1 at 30°C. The eluted analytes were subsequently detected with an UV detector at 254 nm. The effects of organic modifiers and temperature on the enantioselectivity and resolution of the enantiomers were evaluated. The calibration curves were plotted within the concentration range between 2 and 600μg mL-1 (n = 11), and recoveries between 98.74% and 101.52% were obtained, with relative standard deviation < 1.4%. The limit of detection and limit of quantitation for R-enantiomer were 0.94 and 3.07μg mL-1 and for S-enantiomer were 0.86 and 2.84μg mL-1, resp. The validated method was found to be suitable for enantiomeric separation and sufficiently accurate for the determination of enantiomeric purity of EAI045 in bulk drugs.

Journal of Chromatographic Science 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 C11H10ClNO, Product Details of 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

Outlaw, Victor K. published the artcileUnusual blue-shifted acid-responsive photoluminescence behavior in 6-amino-8-cyanobenzo[1,2-b]indolizines, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde, the publication is RSC Advances (2016), 6(66), 61249-61253, database is CAplus and MEDLINE.

6-Amino-8-cyanobenzo[1,2-b]indolizines, a new class of photoluminescent materials, exhibit reversible pH-dependent optical properties characterized by an uncommon and dramatic blue shift in fluorescence emission when protonated. Acid titration and NMR spectroscopy experiments reveal that, rather than the anticipated N-protonation, C-protonation and loss of aromaticity is responsible for the observed photophys. changes. Efficient synthesis from indole-2-carboxaldehydes makes variously substituted versions of this nucleus readily available to tune optical and pH effects.

RSC Advances 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, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde.

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

Qin, Bo published the artcileSrc family kinases (SFK) mediate angiotensin II-induced myosin light chain phosphorylation and hypertension, Recommanded Product: SU6656, the publication is PLoS One (2015), 10(5), e0127891/1-e0127891/7, database is CAplus and MEDLINE.

Angiotensin (Ang) II is the major bioactive peptide of the renin-angiotensin system (RAS); it contributes to the pathogenesis of hypertension by inducing vascular contraction and adverse remodeling, thus elevated peripheral resistance. Ang II also activates Src family kinases (SFK) in the vascular system, which has been implicated in cell proliferation and migration. However, the role of SFK in Ang II-induced hypertension is largely unknown. In this study, we found that administration of a SFK inhibitor SU6656 markedly lowered the level of systemic BP in Ang II-treated mice, which was associated with an attenuated phosphorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant arteries. In the cultured human coronary artery smooth muscle cells (SMCs), pretreatment with SU6656 blocked Ang II-induced MLC phosphorylation and contraction. These results for the first time demonstrate that SFK directly regulate vascular contractile machinery to influence BP. Thus our study provides an addnl. mechanistic link between Ang II and vasoconstriction via SFK-enhanced MLC phosphorylation in SMCs, and suggests that targeted inhibition of Src may provide a new therapeutic opportunity in the treatment of hypertension.

PLoS One 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

Zhang, Chenghu published the artcileCoupling of Integrin α5 to Annexin A2 by Flow Drives Endothelial Activation, Application of SU6656, the publication is Circulation Research (2020), 127(8), 1074-1090, database is CAplus and MEDLINE.

RATIONALE: Atherosclerosis preferentially occurs at specific sites of the vasculature where endothelial cells (ECs) are exposed to disturbed blood flow. Translocation of integrin α5 to lipid rafts promotes integrin activation and ligation, which is critical for oscillatory shear stress (OSS)-induced EC activation. However, the underlying mechanism of OSS promoted integrin α5 lipid raft translocation has remained largely unknown. OBJECTIVE: The objective of this study was to specify the mechanotransduction mechanism of OSS-induced integrin α5 translocation and subsequent EC activation. METHODS AND RESULTS: Mass spectrometry studies identified endothelial ANXA2 (annexin A2) as a potential carrier allowing integrin α5β1 to traffic in response to OSS. Interference by siRNA of AnxA2 in ECs greatly decreased OSS-induced integrin α5β1 translocation to lipid rafts, EC activation, and monocyte adhesion. Pharmacol. and genetic inhibition of PTP1B (protein tyrosine phosphatase 1B) blunted OSS-induced integrin α5β1 activation, which is dependent on Piezo1-mediated calcium influx in ECs. Furthermore, ANXA2 was identified as a direct substrate of activated PTP1B by mass spectrometry. Using bioluminescence resonance energy transfer assay, PTP1B-dephosphorylated ANXA2 at Y24 was found to lead to conformational freedom of the C-terminal core domain from the N-terminal domain of ANXA2. Immunoprecipitation assays showed that this unmasked ANXA2-C-terminal core domain specifically binds to an integrin α5 nonconserved cytoplasmic domain but not β1. Importantly, ectopic lentiviral overexpression of an ANXA2^Y24F mutant increased and shRNA against Ptp1B decreased integrin α5β1 ligation, inflammatory signaling, and progression of plaques at atheroprone sites in apolipoprotein E (ApoE)^-/- mice. However, the antiatherosclerotic effect of Ptp1B shRNA was abolished in AnxA2^-/-ApoE^-/- mice. CONCLUSIONS: Our data elucidate a novel endothelial mechanotransduction mol. mechanism linking atheroprone flow and activation of integrin α5β1, thereby identifying a class of potential therapeutic targets for atherosclerosis.

Circulation 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 C16H12O, Application of 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

Riffell, Jenna L. published the artcileEffects of chemical manipulation of mitotic arrest and slippage on cancer cell survival and proliferation, Related Products of indole-building-block, the publication is Cell Cycle (2009), 8(18), 3029-3042, database is CAplus.

Microtubule-targeting cancer therapies interfere with mitotic spindle dynamics and block cells in mitosis by activating the mitotic checkpoint. Cells arrested in mitosis may remain arrested for extended periods of time or undergo mitotic slippage and enter interphase without having separated their chromosomes. How extended mitotic arrest and mitotic slippage contribute to subsequent cell death or survival is incompletely understood. To address this question, automated fluorescence microscopy assays were designed and used to screen chem. libraries for modulators of mitotic slippage. Chlorpromazine and triflupromazine were identified as drugs that inhibit mitotic slippage and SU6656 and geraldol as chems. that stimulate mitotic slippage. Using the drugs to extend mitotic arrest imposed by low concentrations of paclitaxel led to increased cell survival and proliferation after drug removal. Cells arrested at mitosis with paclitaxel or vinblastine and chem. induced to undergo mitotic slippage underwent several rounds of DNA replication without cell division and exhibited signs of senescence but eventually all died. By contrast, cells arrested at mitosis with the KSP/EgS inhibitor S-trityl-L-cysteine and induced to undergo mitotic slippage were able to successfully divide and continued to proliferate after drug removal. These results show that reinforcing mitotic arrest with drugs that inhibit mitotic slippage can lead to increased cell survival and proliferation, while inducing mitotic slippage in cells treated with microtubule-targeting drugs seems to lead to protracted cell death.

Cell Cycle 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, 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

Prieto, Monica published the artcileArylboronic acids and arylpinacolboronate esters in Suzuki coupling reactions involving indoles. Partner role swapping and heterocycle protection, HPLC of Formula: 642494-36-8, the publication is Journal of Organic Chemistry (2004), 69(20), 6812-6820, database is CAplus and MEDLINE.

Yields of Suzuki couplings involving indoles depended upon (i) whether arylboronic acids or arylpinacolboronate esters were used, (ii) whether the heterocycle was the aryl halide or the arylboron coupling partner, and (iii) whether the heterocycle was protected or not. Highest yields, which were unaffected by incorporating Boc or Tos protection at the heterocyclic nitrogen, were obtained when indole bromides were reacted with phenylboronic acids. When indolylboronic acids were reacted with Ph bromides, yields were somewhat lower and depended on the nitrogen substituent, being highest in the absence of protection, lower in the presence of the Boc group, and lowest of all with the Tos group. Arylpinacolboronate esters were less reactive than arylboronic acids. They required considerably longer reaction times and furnished generally lower yields of biaryl, e.g., I. Furthermore, irresp. of whether the heterocycle was the aryl bromide or the arylpinacolboronate ester, these yields were highest when it was protected with the Tos group. Yields were lower with the Boc group, and unprotected heterocycles gave only traces of biaryl. Careful selection of arylboron reagent, of coupling partner roles, and of protecting groups were essential to ensuring optimum results in these Suzuki couplings.

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, HPLC of Formula: 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

Anraku, Takao published the artcileDecomposition of tryptophan by sulfurous acid salt. III. Isolation and structure of a greenish fluorescent product, Recommanded Product: Potassium 1H-indol-3-yl sulfate, the publication is Yakugaku Zasshi (1966), 86(11), 1043-50, database is CAplus and MEDLINE.

cf. preceding abstracts The substance which shows strong green fluorescence in a solution of tryptophan with a sulfite was isolated and presumed to be dehydroindirubin-1′,2,3,3′-tetrasulfonic acid tetra-Na salt (I). I was considered to be an intermediate in the formation of a red precipitate of indirubin from tryptophan. The formation of I explains well the changes of yellow coloration, green fluorescence to precipitation, and quenching of fluorescence to yellow coloration. It was assumed that the process of this decomposition followed hydrolysis of tryptophan to form indole, serine, and alanine, oxidation of indole with concurrent addition of sulfurous acid to form dehydroindigodisulfonic acid and dehydroindirubintetrasulfonic acid, and formation of various decomposition products by catalytic oxidation in the presence of H or OH ion.

Yakugaku Zasshi 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, Recommanded Product: Potassium 1H-indol-3-yl sulfate.

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

Bryan, George T. published the artcileA sensitive colorimetric method for the determination of urinary indoxyl sulfate (indican), HPLC of Formula: 2642-37-7, the publication is Analytical Biochemistry (1965), 10(1), 120-34, database is CAplus and MEDLINE.

A new, simple, rapid, and precise colorimetric method for urinary indoxyl sulfate (indican) was described. The method was based on preliminary column chromatography on a cation-exchange resin followed by diazotization and coupling. This method of analysis was compared with 2 other methods that have been used for indican analysis. It was found that 18 adult human subjects excreted 331 ± 144 micromoles (83 ± 36 mg.)/24 hrs. This quantity was several times greater than the amount generally believed to be present in human urine.

Analytical Biochemistry 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, HPLC of Formula: 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

Bryant, W. M. D. published the artcileFurther optical crystallographic studies of biochemical substances, Application of Potassium 1H-indol-3-yl sulfate, the publication is Microscope (1989), 37(3), 233-40, database is CAplus.

The optical crystallog. properties of 7 biochems. compounds were measured. Included are D-ribose and D-deoxyribose, structural elements of common nucleic acids; bilirubin, a blood porphyrin degradation product; glucuronic acid, K indoxyl sulfate (urine indican), and cholic acid, agents in human metabolic processes; and 3-flavonol, the parent substance of a series of bioflavonoids of plant origin, believed to be important in human nutrition. Aside from purely descriptive aspects, attention is given to techniques useful in improving precision of measurement and in extending the range of application of the polarizing microscope in the characterization of crystalline organic compounds

Microscope 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, Application of Potassium 1H-indol-3-yl sulfate.

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