Indole Building Blocks

Savall, Brad M. published the artcileDiscovery of Imidazo[1,2-a]pyrazines and Pyrazolo[1,5-c]pyrimidines as TARP γ-8 Selective AMPAR Negative Modulators, Formula: C14H18BNO3, the publication is ACS Medicinal Chemistry Letters (2019), 10(3), 267-272, database is CAplus and MEDLINE.

This report discloses the discovery and characterization of imidazo[1,2-a]pyrazines and pyrazolo[1,5-c]pyrimidines as selective neg. modulators of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) associated with transmembrane AMPAR regulatory protein γ-8. Imidazopyrazine 5 was initially identified as a promising γ-8 selective high-throughput screening hit, and subsequent structure-activity relationship optimization yielded subnanomolar, brain penetrant leads. Replacement of the imidazopyrazine core with an isosteric pyrazolopyrimidine scaffold improved microsomal stability and efflux liabilities to provide 26(I), JNJ-61432059. Following oral administration, 26 exhibited time- and dose-dependent AMPAR/γ-8 receptor occupancy in mouse hippocampus, which resulted in robust seizure protection in corneal kindling and pentylenetetrazole (PTZ) anticonvulsant models.

ACS Medicinal Chemistry 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, Formula: C14H18BNO3.

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

Kim, Jina published the artcileInsights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists, Product Details of C19H28BNO4, the publication is Journal of Medicinal Chemistry (2016), 59(22), 10209-10227, database is CAplus and MEDLINE.

We evaluated the in vitro pharmacol. as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chem. entities that have not only shown to be highly selective agonists for ERRγ, but also exhibited enhanced pharmacokinetic profile than 3 (GSK5182). 6G and 10b had comparable potency to 3 and were far more selective for ERRγ over the ERRα, -β, and ERα. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated as they possessed superior in vitro ADMET profiles compared to the other compounds Addnl., we observed a significant increase of fully-glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b-treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b possess advantageous drug-like properties and can be used to potentially treat various ERRγ-related disorders.

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, Product Details of C19H28BNO4.

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

New, David C. published the artcileBML-190 and AM251 act as inverse agonists at the human cannabinoid CB₂ receptor: signalling via cAMP and inositol phosphates, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is FEBS Letters (2003), 536(1-3), 157-160, database is CAplus and MEDLINE.

The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB₂ and CB₁ receptors, resp. In HEK-293 cells stably expressing the human CB₂ receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB₂ receptor can interact productively with 16z44, a promiscuous Gα_16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB₂ receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB₂ receptor acting via Gα_i/o and Gα_q family-coupled pathways.

FEBS Letters published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone.

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

Yeyeodu, Susan T. published the artcileA rapid, inexpensive high throughput screen method for neurite outgrowth, SDS of cas: 330161-87-0, the publication is Current Chemical Genomics (2010), 74-83, database is CAplus and MEDLINE.

Neurite outgrowth assays are the most common phenotypic screen to assess chem. effects on neuronal cells. Current automated assays involve expensive equipment, lengthy sample preparation and handling, costly reagents and slow rates of data acquisition and anal. We have developed a high throughput screen (HTS) for neurite outgrowth using a robust neuronal cell model coupled to fast and inexpensive visualization methods, reduced data volume and rapid data anal. Neuroscreen-1 (NS-1) cell, a subclone of PC12, possessing rapid growth and enhanced sensitivity to NGF was used as a model neuron. This method reduces preparation time by using cells expressing GFP or native cells stained with HCS CellMask Red in a multiplexed 30 min fixation and staining step. A 2 × 2 camera binning process reduced both image data files and anal. times by 75% and 60% resp., compared to current protocols. In addition, eliminating autofocus steps during montage generation reduced data collection time. Pharmacol. profiles for stimulation and inhibition of neurite outgrowth by NGF and SU6656 were comparable to current standard method utilizing immunofluorescence detection of tubulin. Potentiation of NGF-induced neurite outgrowth by members of a 1,120-member Prestwick compound library as assayed using this method identified six mols., including etoposide, isoflupredone acetate, fludrocortisone acetate, thioguanosine, oxyphenbutazone and gibberellic acid, that more than doubled the neurite mass primed by 2 ng/mL NGF. This simple procedure represents an important routine approach in high throughput screening of large chem. libraries using the neurite outgrowth phenotype as a measure of the effects of chem. mols. on neuronal cells.

Current Chemical Genomics 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 C10H18BNO2, 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

Beall, Howard D. published the artcileIndolequinone Antitumor Agents: Correlation between Quinone Structure, Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase, and in Vitro Cytotoxicity, Category: indole-building-block, the publication is Journal of Medicinal Chemistry (1998), 41(24), 4755-4766, database is CAplus and MEDLINE.

A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl Me position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.

Journal of Medicinal Chemistry 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, 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

Wilkinson, Jonathan D. published the artcileCannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis, HPLC of Formula: 2854-32-2, the publication is Journal of Dermatological Science (2007), 45(2), 87-92, database is CAplus and MEDLINE.

Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterized in part by epidermal keratinocyte hyper-proliferation. We investigated the plant cannabinoids Δ-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR anal. confirmed presence of CB1 and CB2 receptors. The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either CB1/CB2 antagonists. The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.

Journal of Dermatological Science published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C19H14N2, HPLC of Formula: 2854-32-2.

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

Tahata, Eiichi published the artcileMetabolism of indole, Product Details of C8H6KNO4S, the publication is Fukuoka Igaku Zasshi (1959), 4751-67, database is CAplus.

Isolated rabbit liver was perfused with heparinized blood containing indole. After 2-hrs. the perfuzate was deproteinized and treated with an aldehyde reagent. The BuOH extract of the colored substance was subjected to paper chromatography in a isoPrOH-H₂O system. The presence of indole, isatin, indican, anthranilic acid, and urochrome in the perfuzate was demonstrated by comparing their values with those of pure compounds The addition of flavine adenine dinucleotide to the perfuzate enlarged the size of the spots of these compounds except indole.

Fukuoka Igaku 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 C12H14IN, Product Details of C8H6KNO4S.

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

Sprince, Herbert published the artcileA modified Ehrlich benzaldehyde reagent for detection of indoles on paper chromatograms, Name: Potassium 1H-indol-3-yl sulfate, the publication is Journal of Chromatography (1960), 97-8, database is CAplus.

Indole chromatograms, sprayed first with a 2% solution of p-dimethylaminobenzaldehyde in 12.1N HCl, and, after 2-3 min., with 1% aqueous NaO₂, show deep-blue spots which appear immediately. Indican appears as an orange-brown spot and urea as a large deep-yellow spot. Colors developed with this reagent often persist for at least a month without fading.

Journal of Chromatography 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 C65H82N2O18S2, Name: 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

Mueting, Dieter published the artcileDisturbances in protein metabolism in renal insufficiency, Recommanded Product: Potassium 1H-indol-3-yl sulfate, the publication is Protides of the Biological Fluids (1962), 148-54, database is CAplus.

Studies were conducted in 129 patients with renal insufficiency resulting from glomerulonephritis and pyelonephritis. Total serum protein and albumin were decreased and α₁-, α₂– and γ-globulins were increased to an extent proportional to the degree of uremia. Tyrosine and tryptophan were elevated in serum, as well as their phenolic and indolyl catabolites. Increased concentrations of the latter were due not only to decreased urinary excretion but also to decrease oxidative processes. Impairment of oxidation reactions in uremia was also reflected by elevation of sulfate esters. Detoxication processes involving glucuronic acid, as well as sulfate conjugation, are impaired which further aggravates the toxic conditions produced by uremia. The most sensitive criteria of incipient renal insufficiency appeared to be the retention of creatinine and indican, obtained by analyses of their serum and urinary levels.

Protides of the Biological Fluids 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

Melzer, Marvin S. published the artcileApplicability of the Hammett equation to the indole system: acidity of indole-3-carboxylic acids, SDS of cas: 10242-03-2, the publication is Journal of Organic Chemistry (1962), 496-9, database is CAplus.

The acidities of six 5- and 6-substituted indole-3-carboxylic acids were determined in aqueous alc. and their pK plotted against the Hammett substituent constants of the resp. substituents. A good correlation was obtained using the one-term Hammett equation (log K/K° = ρσ) using σ_m for groups in the 5-position and σ_p for groups in the 6-position. These results were taken to indicate thai electronic effects were transmitted to the acid center through the C pare to the 6-position and that virtually no transmission occurred through the indole N atom. It was also found that the 5-bromoindole-3-carboxylic acid (I) was somewhat less acidic than expected, an effect attributed to steric and electronic factors. Infrared data indicated that whereas the 6-aminoindole-3-carboxylic acid (II) existed as the free acid, the 5-amino isomer (III) existed in its zwitterionic form. All pK measurements were made in 50% and 95% alc. and the pH measured using a Beckmann meter. Indole treated with MeMgI then CO₂ gave indote-3-carboxylic acid (IV), m. 214° (decomposition). 5-Nitroindote (.5 g.) treated 1 day in a refrigerator with excess (COCl)₂ gave 5 g. 5-nitroindole-3-glyoxylyl chloride (V), m. 310° (decomposition). V refluxed with KOH gave 3.5 g. 5-nitroindole 3-carboxylic acid (VI), m. 270-2° (decomposition). VI (3.5 g.) refluxed 3 hrs. in refluxing 30% H₂O₂, filtered hot, and the solid further purified gave 2.5 g. 5-nitroindole-3-carboxylic acid (VII), m. 276-8° (decomposition). A portion of V treated directly with 30% H₂O₂ gave 47% VII. V failed to undergo decarboxylation in refluxing tetrachloroethane. VII failed to undergo cleavage on treatment with Pb(OAc)₄ in refluxing AcOH. 5-Bromoindole treated with MeMgl and carbonated gave I, m. 238-40° (decomposition). IV in AcOH treated with HNO₃ gave 6-nitroimtole-3-carboxylic acid (VIII), m. 280-1°. Reduction of VIII in MeOH with Raney Ni under 35 lb./sq. in. H pressure gave II. Another preparation using the same procedure gave a small amount of material, m. 197-9°. VI (500 mg.) in MeOH shaken 8 hrs. with Raney Ni under 50 lb./sq. in. H pressure gave 65 mg. III, m. 177-9° (decomposition). The pK of indole-3-carboxylic acids at 26° were obtained (compound, pK in 50% alc., number of determinations, pK in 95% alc., no of determinations, a used, NH (cm.^-1 given): IV, 7.00, 9, 8.92, 3, 0.00, 3247; VIII, 6.45, 3, 8.06, 2, 0.78, 8425; VI, 6.50, 6, 8.15, 3, 0.71, 3338; I, 6.96, 7, 8.72, 3, 0.391, 3310; 5-ethoxyindote-3-carboxylic acid, 6.98, 6, 8.91, 2, 0.10, 3226; II, 7.43, 2, -, -, -0.66, 3312. Reaction constants and precision of correlation of pK of indole-3-carboxylic acids with Hammett substituent constants were given in a table.

Journal of Organic Chemistry published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, SDS of cas: 10242-03-2.

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