Category: indole-building-block

Masuda, Minoru published the artcileUrinary aromatic metabolites in schizophrenia, Category: indole-building-block, the publication is J. Nervous Mental Disease (1960), 125-33, database is CAplus.

The studies were carried out on 50 acute schizophrenic and 53 nonpsychotic subjects. Overnight urine specimens were prepared as recommended by Dalgleish (CA 51, 3715b) and analyzed by paper chromatography. In the schizophrenics the increased excretion of aromatic compounds was due to indolic, but not phenolic, substances, especially indoleacetic acid, 5-hydroxyindoleacetic acid, and indican. There was also increased excretion of urea. No metabolite was found regularly which would characterize the schizophrenic group.

J. Nervous Mental Disease 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, 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

Lim, Soobin published the artcileCobalt-Catalyzed C-F Bond Borylation of Aryl Fluorides, Product Details of C14H18BNO2, the publication is Organic Letters (2018), 20(22), 7249-7252, database is CAplus and MEDLINE.

A mild and practical Co-catalyzed defluoroborylation of fluoroarenes is presented for the 1st time. The method permits straightforward functionalization of fluoroarenes, with high selectivity for borylation of C-F over C-H bonds, and a tolerance for aerobic conditions. Also, two-step ¹⁸F-fluorination was achieved for expanding the scope of ¹⁸F-positron emission tomog. probes.

Organic Letters 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, Product Details of C14H18BNO2.

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, Xu published the artcileRational Design and Development of Novel CDK9 Inhibitors for the Treatment of Acute Myeloid Leukemia, Formula: C14H18BNO3, the publication is Journal of Medicinal Chemistry (2021), 64(19), 14647-14663, database is CAplus and MEDLINE.

CDK9 is an essential drug target correlated to the development of acute myeloid leukemia (AML). Starting from the hit compound 10, which was discovered through a screening of our inhouse compound library, the structural modifications were carried out based on the bioisosterism and scaffold hopping strategies. Consequently, compound 37 (I) displayed the optimal CDK9 inhibitory activity with an IC₅₀ value of 5.41 nM, which was nearly 1500-fold higher than compound 10. In addition, compound 37 exhibited significant antiproliferative activity in broad cancer cell lines. Further investigation of in vivo properties demonstrated that compound 37 could be orally administrated with an acceptable bioavailability (F = 33.7%). In MV-4-11 s.c. xenograft mouse model, compound 37 (7.5 mg/kg) could significantly suppress the tumor progression with a T/C value of 27.80%. Compound 37 represents a promising lead compound for the development of a novel class of CDK9 inhibitors for the treatment of acute myeloid leukemia.

Journal of Medicinal Chemistry 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

Garg, Neil K. published the artcileThe First Total Synthesis of Dragmacidin D, Formula: C15H14BNO4S, the publication is Journal of the American Chemical Society (2002), 124(44), 13179-13184, database is CAplus and MEDLINE.

The first total synthesis of the biol. significant bis-indole alkaloid dragmacidin D has been achieved. Thermal and electronic modulation provides the key for a series of palladium-catalyzed Suzuki cross-coupling reactions that furnished the core structure of the complex guanidine- and aminoimidazole-containing dragmacidins. Thus, 6-bromo-3-iodo-2-methoxypyrazine was coupled with bromoindole I in the presence of Pd(PPh₃)₄/MeOH/C₆H₆/Na₂CO₃/H₂O to give indolopyrazine II. II was then coupled with another indole under similar conditions to give the core silylated bisindole pyrazine III. Following this crucial sequence, a succession of meticulously controlled final events was developed leading to the completion of the natural product.

Journal of the American Chemical Society 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, Formula: C15H14BNO4S.

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

Haustein, Catherine published the artcileRoom-temperature phosphorescence of 3- and 5-substituted indoles, Safety of Potassium 1H-indol-3-yl sulfate, the publication is Talanta (1989), 36(11), 1065-8, database is CAplus and MEDLINE.

The room-temperature phosphorescence of indole and 13 substituted indoles on filter paper is reported. Cesium and iodide ions increase the emission intensity. In the presence of iodide, the excitation and emission wavelengths of indole are 279 and 440 nm, resp. The excitation and emission wavelengths of indoles with aliphatic groups in the 3-position are 288-289 and 443-449 nm, resp. Indoles with 3,5-substitution have excitation and emission wavelengths of 300-308 and 448-460 nm, resp. Indoxylsulfate and indoxyl-β-D-glucoside were the only indoles surveyed for which variations in the excitation and emission wavelengths depended on the heavy-atom ion present. These compounds had excitation wavelengths ranging from 288 to 388 nm, depending on which heavy-atom perturber was used. Emission wavelengths were 460-500 nm. Log-log plots of intensity vs. concentration were linear between 0.05 and 700 μg/mL for all the compounds studied, with detection limits in the nanogram range.

Talanta 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, Safety 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

Ravula, Suchitra published the artcileLead Optimization of 5-Aryl Benzimidazolone- and Oxindole-Based AMPA Receptor Modulators Selective for TARP γ-8, Category: indole-building-block, the publication is ACS Medicinal Chemistry Letters (2018), 9(8), 821-826, database is CAplus and MEDLINE.

Glutamate mediates fast excitatory neurotransmission via ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The trafficking and gating properties of AMPA receptors (AMPARs) can be amplified by transmembrane AMPAR regulatory proteins (TARPs), which are often expressed in localized brain regions. Herein, the authors describe the discovery, lead optimization, and preclin. characterization of 5-arylbenzimidazolone and oxindole-based neg. modulators of AMPARs associated with TARP γ-8, the primary TARP found in hippocampus. High-throughput screen lead 4 (5-(o-tolyl)indolin-2-one) was optimized for potency and brain penetration to provide benzimidazolone 3, JNJ-55511118. Replacement of the benzimidazolone core in 3 with an oxindole mitigated reactive metabolite formation and led to the identification of 18 (5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-methylindolin-2-one) (GluA1/γ-8 pIC₅₀ = 9.7). Following oral dosing in rats, 18 demonstrated robust target engagement in hippocampus as assessed by ex vivo autoradiog. (ED₅₀ = 0.6 mg/kg, plasma EC₅₀ = 9 ng/mL).

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, 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

Giacomelli, Cristiano published the artcileSpecific Interactions Improve the Loading Capacity of Block Copolymer Micelles in Aqueous Media, Formula: C23H23ClN2O4, the publication is Langmuir (2007), 23(13), 6947-6955, database is CAplus and MEDLINE.

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest mols. and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (weight/weight_p)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND Et ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% weight/weight_p. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by ¹H NMR measurements. However, the incorporation of high numbers of hydrophobic guest mols. inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2R_H) of the objects but also a substantial change in the morphol. (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10^-18-10^-17 cm²/s were determined for IND release from 1.0 mg/mL PEO₁₁₃-b-PDPA₅₀ + 100% weight/weight_p IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.

Langmuir 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, Formula: C23H23ClN2O4.

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

Giacomelli, Cristiano published the artcileLoading capacity of copolymer micelles enhanced by specific interactions, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) (2007), 48(2), 411-412, database is CAplus.

Block copolymer self-assemblies have been successfully tested in many applications as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest mols. and core-forming segments can improve significantly the loading capacity of polymeric micelles. When selected probes exhibiting weak carboxylic acid groups in their structure were loaded into micellar nanoparticles with poly(dialkylamino)ethyl methacrylate-based cores (i.e., weak polybases), high loadings were usually achieved (> 100 % weight/weight of polymer (w/wp)). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was evidenced by 1H NMR measurements, and also through a systematic encapsulation study using structurally different probes and block copolymers.

Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) 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

Al-Ali, Hassan published the artcileChemical Interrogation of the Neuronal Kinome Using a Primary Cell-Based Screening Assay, Application In Synthesis of 330161-87-0, the publication is ACS Chemical Biology (2013), 8(5), 1027-1036, database is CAplus and MEDLINE.

A fundamental impediment to functional recovery from spinal cord injury (SCI) and traumatic brain injury is the lack of sufficient axonal regeneration in the adult central nervous system. There is thus a need to develop agents that can stimulate axon growth to re-establish severed connections. Given the critical role played by protein kinases in regulating axon growth and the potential for pharmacol. intervention, small mol. protein kinase inhibitors present a promising therapeutic strategy. Here, the authors report a robust cell-based phenotypic assay, utilizing primary rat hippocampal neurons, for identifying small mol. kinase inhibitors that promote neurite growth. The assay is highly reliable and suitable for medium-throughput screening, as indicated by its Z’-factor of 0.73. A focused structurally diverse library of protein kinase inhibitors was screened, revealing several compound groups with the ability to strongly and consistently promote neurite growth. The best performing bioassay hit robustly and consistently promoted axon growth in a postnatal cortical slice culture assay. This study can serve as a jumping-off point for structure activity relationship (SAR) and other drug discovery approaches toward the development of drugs for treating SCI and related neurol. pathologies.

ACS Chemical Biology 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, Application In Synthesis 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

Langendorf, Christopher G. published the artcileFake Inhibitors: AMPK Activation Trumps Inhibition, Application of SU6656, the publication is Cell Chemical Biology (2017), 24(7), 775-777, database is CAplus and MEDLINE.

A review. Protein kinase inhibitors have become increasingly important therapeutic drugs for the treatment of human diseases; however, resistance and off-target effects can limit their use. In this issue of Cell Chem. Biol., Ross et al. (2017) reveal a novel off-target mechanism where the Src kinase inhibitor SU6656 paradoxically primes AMPK for phosphorylation and activation by the upstream kinase LKB1.

Cell Chemical Biology 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, 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