Month: November 2022

Liu, Hong published the artcileDesign and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase, Name: 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(24), 126104, database is CAplus and MEDLINE.

Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic benzofuran-based structures were prepared and evaluated. Similar to clin. developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclin. animal species. To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clin. relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.

Bioorganic & Medicinal Chemistry Letters published new progress about 1256359-96-2. 1256359-96-2 belongs to indole-building-block, auxiliary class Indole,Fluoride,Boronic acid and ester,Boronic Acids,Boronate Esters,Boronate Esters, name is 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H17BFNO2, Name: 4-Fluoro-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

Reigan, Philip published the artcileDevelopment of Indolequinone Mechanism-Based Inhibitors of NAD(P)H:Quinone Oxidoreductase 1 (NQO1): NQO1 Inhibition and Growth Inhibitory Activity in Human Pancreatic MIA PaCa-2 Cancer Cells, Synthetic Route of 192820-78-3, the publication is Biochemistry (2007), 46(20), 5941-5950, database is CAplus and MEDLINE.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is currently an emerging target in pancreatic cancer. In this report, we describe a series of indolequinones, based on 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), and evaluate NQO1 inhibition and growth inhibitory activity in the human pancreatic MIA PaCa-2 tumor cell line. The indolequinones with 4-nitrophenoxy, 4-pyridinyloxy, and acetoxy substituents at the (indol-3-yl)methyl position were NADH-dependent inhibitors of recombinant human NQO1, indicative of mechanism-based inhibition. However, those with hydroxy and phenoxy substituents were poor inhibitors of NQO1 enzyme activity, due to attenuated elimination of the leaving group. The ability of this series of indolequinones to inhibit recombinant human NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells. The examination of indolequinone interactions in complex with NQO1 from computational-based mol. docking simulations supported the observed biochem. data with respect to NQO1 inhibition. The design of both NQO1-inhibitory and non-inhibitory indolequinone analogs allowed us to test the hypothesis that NQO1 inhibition was required for growth inhibitory activity in MIA PaCa-2 cells. ES936 and its 6-methoxy analog were potent inhibitors of NQO1 activity and cell proliferation; however, the 4-pyridinyloxy and acetoxy compounds were also potent inhibitors of NQO1 activity but relatively poor inhibitors of cell proliferation. In addition, the phenoxy compounds, which were not inhibitors of NQO1 enzymic activity, demonstrated potent growth inhibition. These data demonstrate that NQO1 inhibitory activity can be dissociated from growth inhibitory activity and suggest addnl. or alternative targets to NQO1 that are responsible for the growth inhibitory activity of this series of indolequinones in human pancreatic cancer.

Biochemistry 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, Synthetic Route of 192820-78-3.

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

Tsai, Henry J. published the artcileA novel hydroxyfuroic acid compound as an insulin receptor activator – structure and activity relationship of a prenylindole moiety to insulin receptor activation, Safety of (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Journal of Biomedical Science (London, United Kingdom) (2009), No pp. given, database is CAplus and MEDLINE.

Background: Diabetes Mellitus is a chronic disease and many patients of which require frequent s.c. insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far. Methods: A series of hydroxyfuroic acid compounds were synthesized and tested for their efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this study. Results and conclusions: This study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potent as compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a moderate inhibitor to EGF receptor. Structure and activity relationship of the prenylindole moiety to insulin receptor activation is discussed.

Journal of Biomedical Science (London, United Kingdom) 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 C6H12F3NO5S, Safety of (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

Paul, Sulagna published the artcileIr-catalyzed functionalization of 2-substituted indoles at the 7-position: Nitrogen-directed aromatic borylation, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Journal of the American Chemical Society (2006), 128(49), 15552-15553, database is CAplus and MEDLINE.

Ir-catalyzed borylation of 2-substituted indoles selectively yielded 7-borylated products, e.g., I (R = H, Cl or OMe) in good yields. N-Protection, required for previous functionalizations of 2-substituted indoles, was unnecessary.

Journal of the American Chemical Society published new progress about 919119-59-8. 919119-59-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO2, Recommanded Product: 2-Methyl-7-(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

Hieda, Yuhzo published the artcileTotal Synthesis of the Neuronal Cell-Protecting Carbazole Alkaloids Carbazomadurin A and (S)-(+)-Carbazomadurin B, COA of Formula: C12H13NO3, the publication is European Journal of Organic Chemistry (2013), 2013(32), 7391-7401, database is CAplus.

The total syntheses of the neuronal cell-protecting carbazole alkaloids carbazomadurin A and (S)-(+)-carbazomadurin B, I [R = Me, (S)-Et, resp.], were achieved. The key step of the synthesis of the polysubstituted carbazole rings included an allene-mediated electrocyclic reaction of the 6π-electron system that involved the indole 2,3-bond. The cleavage of the alkoxy groups of the resulting 3-ethoxy-8-isopropoxycarbazole successfully gave the 3,8-dihydroxycarbazole, which was converted into the 3,8-bis(OSEM)-carbazole (SEM = 2-trimethylsilylethoxymethyl). A Suzuki-Miyaura cross-coupling reaction of the 3,8-bis(OSEM)-carbazole with the corresponding alkenyl pinacol borates afforded the 1-alkenylcarbazoles, which were treated with tetra-n-butylammonium fluoride (TBAF) followed by reduction with NaBH₄ to provide carbazomadurin A and (S)-(+)-carbazomadurin B, resp.

European Journal of Organic Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, COA of Formula: C12H13NO3.

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

Ku, Kyung-Eun published the artcileSrc inhibition induces melanogenesis in human G361 cells, Application In Synthesis of 330161-87-0, the publication is Molecular Medicine Reports (2019), 19(4), 3061-3070, database is CAplus and MEDLINE.

The Src kinase family (SKF) includes non-receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, and is involved in the progression of cellular transformation and oncogenic activity. Therefore, the present study investigated whether C-terminal Src kinase inhibition can induce melanogenesis and examined the associated signaling pathways and mRNA expression of melanogenic proteins. First, whether stimulators of melanogenesis, such as UV B and a-MSH, can dephosphorylate Src protein was evaluated, and the results revealed that SU6656 and PP2 inhibited the phosphorylation of Src in G361 cells. Src inhibition by these chem. inhibitors induced melanogenesis in G361 cells and upregulated the mRNA expression levels of melanogenesis-associated genes encoding microphthalmia-associated transcription factor, tyrosinase-related protein 1 (TRP1), TRP2, and tyrosinase. In addition, Src inhibition by small interfering RNA induced melanogenesis and upregulated the mRNA expression levels of melanogenesis-associated genes. As the p38 mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element binding (CREB) pathways serve key roles in melanogenesis, the present study further examined whether Src mediates melanogenesis via these pathways. Taken together, these data indicate that Src is associated with melanogenesis, and Src inhibition induces melanogenesis via the MAPK and CREB pathways in G361 cells.

Molecular Medicine 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, 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

Mosser, Eric A. published the artcileIdentification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen, SDS of cas: 330161-87-0, the publication is Scientific Reports (2019), 9(1), 1-14, database is CAplus and MEDLINE.

The circadian clock ensures that behavioral and physiol. processes occur at appropriate times during the 24-h day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small mol. screen using a luminescent reporter of mol. circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.

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, 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

Zhao, Di published the artcileFeed-forward activation of STAT3 signaling limits the efficacy of c-Met inhibitors in esophageal squamous cell carcinoma (ESCC) treatment, HPLC of Formula: 330161-87-0, the publication is Molecular Carcinogenesis (2021), 60(7), 481-496, database is CAplus and MEDLINE.

C-Hepatocyte growth factor receptor (Met) inhibitors have demonstrated clin. benefits in some types of solid tumors. However, the efficacy of c-Met inhibitors in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we discovered that c-Met inhibitors induced “Signal Transducer and Activator of Transcription (STAT3)-addiction” in ESCC cells, and the feedback activation of STAT3 in ESCC cells limits the tumor response to c-Met inhibition. Mechanistically, c-Met inhibition increased the autocrine of several cytokines, including CCL2, interleukin 8, or leukemia inhibitory factor, and facilitated the interactions between the receptors of these cytokines and Janus Kinase1/2 (JAK1/2) to resultantly activate JAKs/STAT3 signaling. Pharmacol. inhibition of c-Met together with cytokines/JAKs/STAT3 axis enhanced cancer cells regression in vitro. Importantly, combined c-Met and STAT3 inhibitors synergistically suppressed tumor growth and promoted the apoptosis of tumor cells without producing systematic toxicity. These findings suggest that inhibition of the STAT3 feedback loop may augment the response to c-Met inhibitors via the STAT3-mediated oncogene addiction in ESCC cells.

Molecular Carcinogenesis 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 C9H21NO3, HPLC of Formula: 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

Zhu, Wei published the artcileDesign, Synthesis, and Pharmacological Evaluation of Novel Multisubstituted Pyridin-3-amine Derivatives as Multitargeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer, COA of Formula: C14H18BNO3, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6018-6035, database is CAplus and MEDLINE.

A novel series of pyridin-3-amine derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments The structure-activity relationship (SAR) of its analogs was then explored to afford novel FGFR inhibitors. Among them, I showed potent inhibition against FGFR1, 2, and 3. Interestingly, compound I not only inhibited various phosphorylation and downstream signaling across different oncogenic forms in FGFR-overactivated cancer cells but also showed nanomolar level inhibition against several other NSCLC-related oncogene kinases, including RET, EGFR, EGFR/T790M/L858R, DDR2, and ALK. Finally, in vivo pharmacol. evaluations of I showed significant antitumor activity (TGI = 66.1%) in NCI-H1581 NSCLC xenografts with a good pharmacokinetic profile.

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 C5H6N2O2, COA of 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

Matsuo, Yusuke published the artcileFacile synthesis of fluorescent hetero[8]circulene analogues with tunable solubilities and optical properties, Synthetic Route of 683229-62-1, the publication is Chemical Science (2019), 10(48), 11006-11012, database is CAplus and MEDLINE.

Hetero[8]circulenes are an interesting class of polycyclic heteroaromatic mols. having rigid and planar structures, which are promising in light of their potential applications for OLEDs, OFETs and so forth. Although their synthetic methods have been developed in some specific cases, a facile synthetic protocol of novel hetero[8]circulenes with tunable properties is highly desirable. We herein report the unexpected formation of methoxy-substituted quasi-aza[8]circulene and its conversion into unprecedented triazaoxa[8]circulene. The structures and optical properties were comparatively studied. Remarkably, triazaoxa[8]circulene is highly soluble in THF, acetone and DMSO mainly because of effective hydrogen-bonding of the NH moieties to these solvents. Their highly soluble nature in various solvents enabled us to study the solvent effects of these mols. In particular, triazaoxa[8]circulene displays a high fluorescence quantum yield of 0.72 in DMSO. Furthermore, enantiomeric separation of highly distorted quasi-aza[8]circulene was successfully achieved by chiral HPLC. Thus, these novel hetero[8]circulene derivatives are practically useful fluorescent nanographene-like mols. with intriguing optical properties.

Chemical Science published new progress about 683229-62-1. 683229-62-1 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Ether,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 5-Methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO3, Synthetic Route of 683229-62-1.

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