Day: November 28, 2022

Zhang, Qiang published the artcileIn vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB₂) in rat liver microsomes, Safety of 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is European Journal of Pharmaceutical Sciences (2010), 41(1), 163-172, database is CAplus and MEDLINE.

The in vitro metabolism of an inverse agonist of the peripheral cannabinoid receptor (CB₂), indomethacin morpholinylamide (BML-190), has been characterized using rat liver microsomal incubation. BML-190 was found to yield at least 15 metabolic products as identified by HPLC-MS/MS anal. Four major phase one metabolic pathways either individually, or in combination, were proposed to account for the identified metabolic products: (1) loss of the p-chlorobenzyl group, (2) hydroxylation on the indole or on the morpholine ring, (3) morpholinyl ring opening, and (4) demethylation of the methoxyl group on the indole ring.

European Journal of Pharmaceutical Sciences 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 C8H7NO4, 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

Gao, Xiaodong published the artcileUpregulation of ZNF148 in SDHB-deficient gastrointestinal stromal tumor potentiates Forkhead box M1-mediated transcription and promotes tumor cell invasion, Formula: C19H21N3O3S, the publication is Cancer Science (2020), 111(4), 1266-1278, database is CAplus and MEDLINE.

Succinate dehydrogenase (SDH) deficiency is associated with gastrointestinal stromal tumor (GIST) oncogenesis, but the underlying mol. mechanism remains to be further investigated. Here, we show that succinate accumulation induced by SDHB loss of function increased the expression of zinc finger protein 148 (ZNF148, also named ZBP-89) in GIST cells. Meanwhile, ZNF148 is found to be phosphorylated by ERK at Ser306, and this phosphorylation results in ZNF148 binding to Forkhead box M1 (FOXM1). Through the complex formation at the promoter, ZNF148 facilitates Histone H3 acetylation and FOXM1-mediated Snail transcription, which eventually promotes cell invasion and tumor growth. The clin. anal. indicates that SDHB deficiency is associated with elevated ZNF148 levels, and ZNF148-S306 phosphorylation level displays a pos. correlation with poor prognosis in GIST patients. These findings illustrate an unidentified mol. mechanism underlying FOXM1-regulated gene transcription related to GIST cell invasion, which highlights the physiol. effects of SDHB deficiency on the invasiveness of GIST.

Cancer Science 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, Formula: 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

Liu, Yonggui published the artcileCarbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones, Category: indole-building-block, the publication is Angewandte Chemie, International Edition (2020), 59(1), 442-448, database is CAplus and MEDLINE.

The aromatic nitrogen atoms of heteroarylaldehydes were activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products I [R¹ = H, 8′-Br, 7′-Cl, etc.; R² = H, 4-Br, 5-Cl, etc.; R³ = Me, Bn, Trt], II [R¹ = H, 8-Br, 7-F, etc.; R² = H, 3-Me, 4-Cl, etc.; R³ = Me, Et, Ph, Bn, CHPh₂] and III [R¹ = H, 6;t-Bu, 7’Cl, etc.; R² = H, 4-Cl, 5-Me, etc.] were afforded in good to excellent yields and optical purities. Reaction involved the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibited excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichems. for plant protection.

Angewandte Chemie, International Edition 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, 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

Gomes, Joao R. published the artcileBDNF-Induced Intracellular Signaling, Product Details of C19H21N3O3S, the publication is Neuromethods (2019), 161-183, database is CAplus.

The neurotrophin BDNF plays important roles in neuronal survival, growth, and differentiation during development. Furthermore, it has been shown to mediate long-term changes in the synaptic activity in the hippocampus and in other brain regions, which are thought to underlie learning and memory formation. Cultured hippocampal neurons express TrkB receptors and, therefore, constitute a valuable exptl. model to study in vitro BDNF-induced intracellular signaling pathways. In this chapter, we describe (1) the methodol. used to prepare cultured hippocampal neurons from mice (wild-type-WT or transgenic animals) and rats and (2) three different approaches to investigate BDNF signaling: Western blot and Bio-Plex for overall signaling activity and immunocytochem. to analyze where signaling activity takes place in neurons. The Bio-Plex approach allows the simultaneous characterization of different pathways using small sample volumes and within a short period of time.

Neuromethods 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

Wang, Ke published the artcileSynthesis of Arcyriarubin A and Arcyriaflavin A via Cross-Coupling of Indolylboronic Acid with Dibromomaleimides, Recommanded Product: (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Synthetic Communications (2010), 40(1), 144-150, database is CAplus.

Arcyriarubin A (I) was first isolated by Steglich in 1980 and is also a key intermediate in the synthesis of indolocarbazole alkaloids. A new synthetic approach to the natural products arcyriaflavin A (II) and arcyriarubin A was described. The key step was a Suzuki cross-coupling reaction which was achieved by refluxing 1-tosyl-3-indolylboronic acid, 1-methyl-3,4-dibromomaleimide, Pd(PPh₃)₄ and Na₂CO₃ in dioxane/MeOH. The preparation of arcyriaflavin A was accomplished in eight steps from indole with an overall yield of 21%.

Synthetic Communications 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 C15H21BO2, Recommanded Product: (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

Wen, Hui published the artcileDesign and synthesis of indoleamine 2,3- Dioxygenase 1 inhibitors and evaluation of their use as anti-tumor agents, Application of 6-Nitro-1H-indole-3-carboxylic acid, the publication is Molecules (2019), 24(11), 2124, database is CAplus and MEDLINE.

Indoleamine 2,3-dioxygenase (IDO) 1 is the key enzyme for regulating tryptophan metabolism and is an important target for interrupting tumor immune escape. In this study, we designed four series of compounds as potential IDO1 inhibitors by attaching various fragments or ligands to indole or phenylimidazole scaffolds to improve binding to IDO1. The compounds were synthesized and their inhibitory activities against IDO1 and tryptophan 2,3-dioxygenase were evaluated. Two compounds with a phenylimidazole scaffold (DX-03-12 and DX-03-13) showed potent IDO1 inhibition with IC₅₀ values of 0.3-0.5μM. These two IDO1 inhibitors showed low cell cytotoxicity, which indicated that they may exert their anti-tumor effect via immune modulation. Compound DX-03-12 was investigated further by determining the in vivo pharmacokinetic profile and anti-tumor efficacy. The pharmacokinetic study revealed that DX-03-12 had satisfactory properties in mice, with rapid absorption, moderate plasma clearance (~36% of hepatic blood flow), acceptable half-life (~4.6 h), and high oral bioavailability (~96%). Daily oral administration of 60 mg/kg of compound DX-03-12 decreased tumor growth by 72.2% after 19 days in a mouse melanoma cell B16-F10 xenograft model compared with the untreated control. Moreover, there was no obvious weight loss in DX-03-12-treated mice. In conclusion, compound DX-03-12 is a potent lead compound for developing IDO1 inhibitors and anti-tumor agents.

Molecules 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 C8H14O2, Application of 6-Nitro-1H-indole-3-carboxylic 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

Jingwen, E. published the artcileHow different substitution positions of F, Cl atoms in benzene ring of 5-methylpyrimidine pyridine derivatives affect the inhibition ability of EGFRL⁸⁵⁸R/T⁷⁹⁰M/C⁷⁹⁷S inhibitors: a molecular dynamics simulation study, Computed Properties of 1942114-09-1, the publication is Molecules (2020), 25(4), 895, database is CAplus and MEDLINE.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, and mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are a common cause of non-small-cell lung cancers, which is a major subtype of lung cancers. Recently, a series of 5-methylpyrimidine-pyridinone derivatives have been designed and synthesized as novel selective inhibitors of EGFR and EGFR mutants. However, the binding-based inhibition mechanism has not yet been determined In this study, we carried out mol. dynamic simulations and free-energy calculations for EGFR derivatives to fill this gap. Based on the investigation, the three factors that influence the inhibitory effect of inhibitors are as follows: (1) The substitution site of the Cl atom is the main factor influencing the activity through steric effect; (2) The secondary factors are repulsion between the F atom (present in the inhibitor) and Glu762, and the blocking effect of Lys745 on the Ph ring of the inhibitor. (3) The two factors function synergistically to influence the inhibitory capacity of the inhibitor. The theor. results of this study can provide further insights that will aid the design of oncogenic EGFR inhibitors with high selectivity.

Molecules 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, Computed Properties of 1942114-09-1.

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

Schyman, Patric published the artcileGeneral Purpose 2D and 3D Similarity Approach to Identify hERG Blockers, Application In Synthesis of 2854-32-2, the publication is Journal of Chemical Information and Modeling (2016), 56(1), 213-222, database is CAplus and MEDLINE.

Screening compounds for human ether-á-go-go-related gene (hERG) channel inhibition is an important component of early stage drug development and assessment. In this study, we developed a high-confidence (p-value < 0.01) hERG prediction model based on a combined two-dimensional (2D) and three-dimensional (3D) modeling approach. We developed a 3D similarity conformation approach (SCA) based on examining a limited fixed number of pairwise 3D similarity scores between a query mol. and a set of known hERG blockers. By combining 3D SCA with 2D similarity ensemble approach (SEA) methods, we achieved a maximum sensitivity in hERG inhibition prediction with an accuracy not achieved by either method sep. The combined model achieved 69% sensitivity and 95% specificity on an independent external data set. Further validation showed that the model correctly picked up documented hERG inhibition or interactions among the Food and Drug Administration- approved drugs with the highest similarity scores-with 18 of 20 correctly identified. The combination of ascertaining 2D and 3D similarity of compounds allowed us to synergistically use 2D fingerprint matching with 3D shape and chem. complementarity matching.

Journal of Chemical Information and Modeling 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 C25H23NO4, Application In Synthesis of 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

Heiss, Elke H. published the artcilePlumericin inhibits proliferation of vascular smooth muscle cells by blocking STAT3 signaling via S-glutathionylation, Computed Properties of 330161-87-0, the publication is Scientific Reports (2016), 20771, database is CAplus and MEDLINE.

The etiol. of atherosclerosis and restenosis involves aberrant inflammation and proliferation, rendering compounds with both anti-inflammatory and anti-mitogenic properties as promising candidates for combating vascular diseases. A recent study identified the iridoid plumericin as a new scaffold inhibitor of the pro-inflammatory NF-κB pathway in endothelial cells. We here examined the impact of plumericin on the proliferation of primary vascular smooth muscle cells (VSMC). Plumericin inhibited serum-stimulated proliferation of rat VSMC. It arrested VSMC in the G1/G0-phase of the cell cycle accompanied by abrogated cyclin D1 expression and hindered Ser 807/811-phosphorylation of retinoblastoma protein. Transient depletion of glutathione by the electrophilic plumericin led to S-glutathionylation as well as hampered Tyr705-phosphorylation and activation of the transcription factor signal transducer and activator of transcription 3 (Stat3). Exogenous addition of glutathione markedly prevented this inhibitory effect of plumericin on Stat3. It also overcame downregulation of cyclin D1 expression and the reduction of biomass increase upon serum exposure. This study revealed an anti-proliferative property of plumericin towards VSMC which depends on plumericin’s thiol reactivity and S-glutathionylation of Stat3. Hence, plumericin, by targeting at least two culprits of vascular dysfunction -inflammation and smooth muscle cell proliferation -might become a promising electrophilic lead compound for vascular disease therapy.

Scientific Reports 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, Computed Properties 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

Zou, Ning published the artcileSolution-Phase Synthesis of a Thiazoyl-Substituted Indolyl Library via Suzuki Cross-Coupling, Name: (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Journal of Combinatorial Chemistry (2003), 5(6), 754-755, database is CAplus and MEDLINE.

The solution phase synthesis of a thiazolyl substituted indolyl library using a Suzuki cross-coupling of 2-chlorothiazole and N-tosyl-3-indolylboronic acids is presented. This library is being evaluated for biol. activity and is a part of a further study for pharmaceutical drug discovery.

Journal of Combinatorial Chemistry 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 C34H40F2S4, Name: (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