Day: February 22, 2023

Synthesis of Rucaparib-a poly (ADP-ribose) polymerase inhibitor was written by Geng, Yuan-shuo;Hu, Po;Wang, Xin;Liu, Chao;Li, Zhi-yu. And the article was included in Jingxi Huagong Zhongjianti in 2012.Safety of 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate This article mentions the following:

Rucaparib is the first poly(ADP-ribose) polymerase (PARP) inhibitor which entered into the clin. trial. It was prepared in 5.38% overall yield in 12 steps by using 5-fluoro-2-methylbenzoic acid as the starting material. The synthetic process was designed as a novel method with less toxicity and easy operation. The structures of the intermediates and the final product were identified with MS and ¹H NMR. In the experiment, the researchers used many compounds, for example, 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate (cas: 459868-92-9Safety of 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate).

8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate (cas: 459868-92-9) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Safety of 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Chemotaxonomic classification applied to the identification of two closely-related Citrus TCMs using UPLC-Q-TOF-MS-based metabolomics was written by Zhao, Si-Yu;Liu, Zhen-Li;Shu, Yi-Song;Wang, Meng-Lei;He, Dan;Song, Zhi-Qian;Zeng, Hong-Lian;Ning, Zhang-Chi;Lu, Cheng;Lu, Ai-Ping;Liu, Yuan-Yan. And the article was included in Molecules in 2017.SDS of cas: 16502-01-5 This article mentions the following:

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive anal. of small mol. metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling anal. was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, anal. of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses. In the experiment, the researchers used many compounds, for example, 2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indole (cas: 16502-01-5SDS of cas: 16502-01-5).

2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indole (cas: 16502-01-5) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.SDS of cas: 16502-01-5

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Molecular mechanism of Gleditsiae Spina for the treatment of high-grade serous ovarian cancer based on network pharmacology and pharmacological experiments was written by Zhang, Boran;Dan, Wenchao;Zhang, Ganlin;Wang, Xiaomin. And the article was included in BioMed Research International in 2022.Computed Properties of C11H12N2O2 This article mentions the following:

Gleditsiae Spina, widely used in traditional Chinese medicine, has a good curative effect on malignant tumors such as ovarian cancer, but the mechanism is not clear. So, we aimed to analyze the pharmacol. mechanism of Gleditsiae Spina in the treatment of high-grade serous ovarian cancer (HGSC) based on network pharmacol. and biol. experiments The main active ingredients of Gleditsiae Spina were identified by high performance liquid chromatog. (HPLC) and mass spectrometry (MS), and the active ingredients were performed by ADME screening. The component targets of Gleditsiae Spina were screened using the PharmMapper platform, and differentially expressed genes in normal and HGSC tissues were identified through the GEO database. Thereafter, the network of “active ingredient-targets” was constructed by cytoscape 3.7.2 software. The protein-protein interaction network was established by the BioGenet database to mine the potential protein function. Biol. processes and pathways were analyzed through Gene Ontol. and Kyoto Encyclopedia of Genes and Genomes anal. The binding ability of the core components of the Gleditsiae Spina and the core target of HGSC was verified by mol. docking and mol. dynamics simulation, and the therapeutic effect of Gleditsiae Spina was proved in vitro through cytotoxicity experiments The effect of Gleditsiae Spina on the core pathway is obtained by western blotting. Gleditsiae Spina had cytotoxicity on HGSC based on network pharmacol. and biol. experiments Luteolin, genistein, D-(+)-tryptophan, ursolic acid, and berberine are the identified core active ingredients of Gleditsiae Spina for regulating HGSC, with HPSE, PI3KCA, AKT1, and CTNNB1as the ideal targets. The prediction results were verified by mol. docking, mol. dynamic simulation, cell viability, and western blot anal. Gleditsiae Spina mainly downregulates the expression of heparanase and β-catenin to affect the composition of tumor cytoplasmic matrix and can regulate the PI3K-AKT pathway, integrating multiple targets and multiple pathways to play a therapeutic role. It also provides a theor. basis for the prevention of ovarian cancer and its treatment using traditional Chinese medicine in the future. In the experiment, the researchers used many compounds, for example, H-D-Trp-OH (cas: 153-94-6Computed Properties of C11H12N2O2).

H-D-Trp-OH (cas: 153-94-6) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Computed Properties of C11H12N2O2

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Palladium Metallaphotoredox-Catalyzed 2-Arylation of Indole Derivatives was written by Wang, Xinmou;Xun, Xiwei;Song, Hongjian;Liu, Yuxiu;Wang, Qingmin. And the article was included in Organic Letters in 2022.SDS of cas: 1016-47-3 This article mentions the following:

Herein, a two-step method for C(sp2)-H/C(sp2)-H cross-coupling reactions was reported to synthesize 2-arylindole derivatives I [R¹ = H, 4-Me, 5-I, etc.; Ar = 4-t-BuC₆H₄, 4-PhOC₆H₄, 3-Br-4-MeOC₆H₃, etc.] by combining palladium catalysis and photocatalysis. This mild, dual-catalysis method showed good functional group tolerance and a wide substrate scope and could be used for late-stage functionalization of oligopeptides, drugs, and natural products. In the experiment, the researchers used many compounds, for example, N-(2-(1H-Indol-3-yl)ethyl)acetamide (cas: 1016-47-3SDS of cas: 1016-47-3).

N-(2-(1H-Indol-3-yl)ethyl)acetamide (cas: 1016-47-3) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.SDS of cas: 1016-47-3

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Attenuation of the degenerative effects of endothelin-1 on cartilaginous end plate cells by the endothelin receptor antagonist BQ-123 via the Wnt/β-catenin signaling pathway. was written by Yuan, Wei;Li, Zhen-Xi;Zhao, Cheng-Long;Hou, Tian-Hui;Hu, Si-Wang;Liu, Wei-Bo;Yuan, Feng-Lai;Xiao, Jian-Ru. And the article was included in The spine journal : official journal of the North American Spine Society in 2018.COA of Formula: C31H42N6O7 This article mentions the following:

BACKGROUND CONTEXT: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage end plate (CEP) degeneration in the intervertebral disc (IVD). SOX9 is downregulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/β-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin-A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous end plate cells (CECs) associated with CEP degeneration via the Wnt/β-catenin signaling pathway. STUDY DESIGN/SETTING: The influence of ET-1 on the expression levels of collagen II, aggrecan, and SOX9 in CECs and the effect of BQ-123 in this context were investigated. METHODS: To establish a model for CEP degeneration, three lumbar discs (L3-L4, L4-L5, and L5-L6 levels) in New Zealand white rabbits were punctured close to the vertebral end plate using a 14G needle. Intervertebral disc degeneration was evaluated by magnetic resonance imaging 4 weeks after vertebral end plate injury. CECs were then isolated from the degenerated CEPs to allow evaluation of the role of ET-1 and BQ-123 and to investigate their effects on the Wnt/β-catenin signaling pathway. The expression of ET-1 in CECs from degenerated CEPs was analyzed by immunofluorescent staining. Changes in the levels of collagen II, aggrecan, and SOX9 were evaluated in CECs by real-time polymerase chain reaction and by Western blotting. The Wnt/β-catenin signaling pathway was also investigated by Western blotting. RESULTS: After 4 weeks, IVDs with vertebral end plate injury exhibited clear signs of disc degeneration. Immunofluorescent staining showed that ET-1 was expressed in the cytoplasm of CECs. Endothelin-1 stimulation significantly inhibited the expression of collagen II, aggrecan, and SOX9 in CECs, whereas BQ-123 increased the levels of these three molecules. In addition, ET-1 stimulation increased the expression of β-catenin, cyclin D1, and Dvl1 in the Wnt/β-catenin signaling pathway of CECs from degenerated discs and reduced the expression of GSK-3β, whereas BQ-123 had the opposite effect. CONCLUSIONS: Endothelin-1 can reduce levels of collagen II, aggrecan, and SOX9 in CECs through activation of the Wnt/β-catenin signaling pathway, whereas BQ-123 attenuates these negative effects, highlighting a new molecular mechanism with potential for exploitation for treatment of CEP degeneration. In the experiment, the researchers used many compounds, for example, 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6COA of Formula: C31H42N6O7).

2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.COA of Formula: C31H42N6O7

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease was written by Prado, Gregory N.;Romero, Jose R.;Rivera, Alicia. And the article was included in FASEB Journal in 2013.Name: 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid This article mentions the following:

Increased endothelin-1 (ET-1) levels, disordered thiol protein status, and erythrocyte hydration status play important roles in sickle cell disease (SCD) through unresolved mechanisms. Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions. We provide evidence that PDI is present in human and mouse erythrocyte membranes and that selective blockade with monoclonal antibodies against PDI leads to reduced Gardos channel activity (1.6 ± 0.03 to 0.56 ± 0.02 mmol·10¹³ cell^-1·min^-1, P<0.001) and d. of sickle erythrocytes (D₅₀: 1.115 ± 0.001 to 1.104 ± 0.001 g/mL, P = 0.012) with an IC₅₀ of 4 ng/mL. We observed that erythrocyte associated-PDI activity was increased in the presence of ET-1 (3.1 ± 0.2 to 5.6 ± 0.4%, P<0.0001) through a mechanism that includes casein kinase II. Consistent with these results, in vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists lowered circulating and erythrocyte associated-PDI activity (7.1 ± 0.3 to 5.2 ± 0.2%, P<0.0001) while improving hematol. parameters and Gardos channel activity. Thus, our results suggest that PDI is a novel target in SCD that regulates erythrocyte volume and oxidative stress and may contribute to cellular adhesion and endothelial activation leading to vasoocclusion as observed in SCD. In the experiment, the researchers used many compounds, for example, 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6Name: 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid).

2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid (cas: 136553-81-6) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Name: 2-((3R,6S,9R,12R,17aS)-9-((1H-Indol-3-yl)methyl)-6-isobutyl-3-isopropyl-1,4,7,10,13-pentaoxohexadecahydro-1H-pyrrolo[1,2-a][1,4,7,10,13]pentaazacyclopentadecin-12-yl)acetic acid

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Convenient synthesis of chiral tryptophan derivatives using Negishi cross-coupling was written by Tanaka, Minoru;Hikawa, Hidemasa;Yokoyama, Yuusaku. And the article was included in Tetrahedron in 2011.Category: indole-building-block This article mentions the following:

A facile synthetic procedure for chiral tryptophan derivatives using Negishi cross-coupling reaction of serine-derived iodoalanine with 3-haloindole is described. The best result was obtained when the reaction of N-tosyl-3-bromoindole with N-Cbz-iodoalanine Me ester (Cbz = benzyloxycarbonyl) was carried out by the combination of Pd₂(dba)₃ and sterically hindered ferrocenyl ligand Q-PHOS. This reaction condition not only gave the desired tryptophan derivative as high as 76% yield, but also suppressed the formation of undesired products, the dehalogenated indole and the homodimer of indole, which were difficult to sep. This reaction was extended to the synthesis of various tryptophan derivatives having substituents on the benzene ring. The characteristic of this reaction is the practical biomimetic synthesis of chiral tryptophan derivatives in one-step. In the experiment, the researchers used many compounds, for example, 4-Nitroindole (cas: 4769-97-5Category: indole-building-block).

4-Nitroindole (cas: 4769-97-5) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Category: indole-building-block

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bromocontryphan: post-translational bromination of tryptophan was written by Jimenez, Elsie C.;Craig, A. Grey;Watkins, Maren;Hillyard, David R.;Gray, William R.;Gulyas, Joseph;Rivier, Jean;Cruz, Lourdes J.;Olivera, Baldomero M.. And the article was included in Biochemistry in 1997.SDS of cas: 52448-17-6 This article mentions the following:

The authors demonstrate that post-translational bromination of a tryptophan residue occurs in the biol. active octapeptide bromocontryphan, purified and characterized from Conus radiatus venom. Clones encoding bromocontryphan were identified from a cDNA library made from C. radiatus venom ducts. The mRNA sequence obtained predicts a prepropeptide which has the mature peptide sequence at the C-terminal end, with the L-6-bromotryptophan residue encoded by UGG, the Trp codon. These data provide the first direct evidence for post-translational bromination of a polypeptide which is translated through the normal cellular machinery. In addition to bromination, the peptide, which induces a “stiff tail” syndrome in mice, has several other modifications, including hydroxylation of Pro³, epimerization of Trp⁴, and C-terminal amidation. Bromocontryphan appears to have the highest d. of post-translational modifications known among gene-encoded polypeptides. The overall result is a mol. which closely resembles marine natural products produced through specialized biosynthetic pathways comprising many enzyme-catalyzed steps. In the experiment, the researchers used many compounds, for example, (S)-2-Amino-3-(6-bromo-1H-indol-3-yl)propanoic acid (cas: 52448-17-6SDS of cas: 52448-17-6).

(S)-2-Amino-3-(6-bromo-1H-indol-3-yl)propanoic acid (cas: 52448-17-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.SDS of cas: 52448-17-6

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Copper-Catalyzed Intermolecular Trifluoromethylthiocyanation of Alkenes: Convenient Access to CF₃-Containing Alkyl Thiocyanates was written by Liang, Zhaoli;Wang, Fei;Chen, Pinhong;Liu, Guosheng. And the article was included in Organic Letters in 2015.HPLC of Formula: 5428-09-1 This article mentions the following:

A highly selective and efficient approach for the direct trifluoromethylthiocyanation of alkenes has been developed using trimethylsilyl isothiocyanate (TMSNCS) as the thiocyanating agent and Togni reagent as the CF₃ source in the presence of copper(I) catalyst. Both activated and unactivated alkenes work well to deliver various CF₃-containing thiocyanates. In the experiment, the researchers used many compounds, for example, 2-Allylisoindoline-1,3-dione (cas: 5428-09-1HPLC of Formula: 5428-09-1).

2-Allylisoindoline-1,3-dione (cas: 5428-09-1) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Moreover, it is known that it controls biofilm formation. However, the role of indole in the cell has not been fully elucidated.HPLC of Formula: 5428-09-1

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Functionalisation of isoindolinones via a calcium catalysed Hosomi-Sakurai allylation was written by Basson, Ashley J.;McLaughlin, Mark G.. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2019.Category: indole-building-block This article mentions the following:

A rapid and functionally tolerant calcium catalyzed Hosomi-Sakurai reaction has been realized. Employing 1 mol% calcium, allylated isoindolinones I (R¹ = H, C₆H₅, 4-F₃CC₆H₄, thien-2-yl, 1H-benzodioxol-5-yl, etc.; R² = H, Me, allyl, benzyl; R³ = H, CH₃, 4-BrC₆H₄) can be synthesized in high yields and the reaction is shown to be tolerant to a range of medicinally relevant functional groups including heterocycles. The synthetic utility of the reaction has been shown, and a plausible reaction mechanism is provided. In the experiment, the researchers used many compounds, for example, 2-Allylisoindoline-1,3-dione (cas: 5428-09-1Category: indole-building-block).

2-Allylisoindoline-1,3-dione (cas: 5428-09-1) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Category: indole-building-block

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles