Day: November 21, 2022

El-Gendy, Adel A. published the artcileSynthesis and antihypertensive activity of certain Mannich bases of 2-ethoxycarbonylindoles and 5H-pyridazino[4,5-b]indoles, SDS of cas: 100123-25-9, the publication is Archives of Pharmacal Research (2001), 24(1), 21-26, database is CAplus and MEDLINE.

The synthesis of 3-(aminomethyl)-1H-indole-2-carboxylic acid Et ester derivatives and of 3-(aminomethyl)-3,5-dihydro-4H-pyridazino[4,5-b]indol-4-one derivatives was reported. Fourteen of the synthesized Mannich bases were screened as antihypertensive agents in normotensive anesthetized rats. The effect of 3-[(diethylamino)methyl]-1H-indole-2-carboxylic acid Et ester hydrochloride in normotensive anesthetized dogs was also studied.

Archives of Pharmacal Research published new progress about 100123-25-9. 100123-25-9 belongs to indole-building-block, auxiliary class Indole,Bromide,Ester,Aldehyde, name is Ethyl 5-bromo-3-formyl-1H-indole-2-carboxylate, and the molecular formula is C12H10BrNO3, SDS of cas: 100123-25-9.

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

Anderson, Kirsty published the artcileOne-pot oxidative hydrolysis-oxidative cleavage of 7-borylindoles enables access to o-amidophenols and 4-acylbenzoxazoles, COA of Formula: C15H20BNO2, the publication is Chemical Communications (Cambridge, United Kingdom) (2020), 56(24), 3559-3562, database is CAplus and MEDLINE.

The compounds 7-borylindoles I (R¹ = H, Me, n-Pr, BPin, Ph, 4-fluorophenyl; R² = H, Me, Et, 4-methoxyphenyl; R³ = H, Me, F, Cl, Br, NO₂, BnO) undergo a one-pot oxidative-hydrolysis of the arylboronate and oxidative cleavage of the indole C2-C3 double bond to afford o-amidophenol derivatives 2-OH-4-R³-6-(R²C(O))-C₆H₂NHC(O)R¹. Subsequent cyclization delivers benzoxazoles II bearing an acyl group at C4, a substitution pattern common to fungal-derived benzoxazole alkaloids. Using 7-borylindoles I as substrates to access functionalized o-amidophenols, the difficult preparation of these compounds from arene, streamlining access to substituted 4-acylbenzoxazoles II in the process is circumvented.

Chemical Communications (Cambridge, United Kingdom) 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, COA of Formula: C15H20BNO2.

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

Hara, Toshiaki published the artcileProbing the Structural Requirements of Peptoids That Inhibit HDM2-p53 Interactions, Safety of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Journal of the American Chemical Society (2006), 128(6), 1995-2004, database is CAplus and MEDLINE.

Many cellular processes are controlled by protein-protein interactions, and selective inhibition of these interactions could lead to the development of new therapies for several diseases. For example, overexpression of the protein HDM2 (human double minute 2), which binds to and inactivates the protein p53, has been linked to tumor aggressiveness and drug resistance in cancer. In creating inhibitors of protein-protein interactions, one strategy is to recreate the three-dimensional arrangement of side chains that are involved in the binding of one protein to another, using a nonnatural scaffold as the attachment point for the side chains. Here, the authors used oligomeric peptoids as the scaffold to develop a general strategy to rationally design synthetic mols. that can be optimized for inhibition of protein-protein interactions. Structural information on the HDM2-p53 complex was used to design the first class of peptoid inhibitors, and this work provides, in detail, the strategy to modify peptoids with the appropriate side chains that are effective inhibitors of HDM2-p53 binding. While the authors initially tried to develop rigid, helical peptoids as HDM2 binders, the best inhibitors were surprisingly peptoids that lacked any helix-promoting groups. These results indicate that starting with rigid peptoid scaffolds may not always be optimal to develop new inhibitors.

Journal of the American Chemical Society published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Safety of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

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

Gallant, Michel published the artcileNew class of potent ligands for the human peripheral cannabinoid receptor, SDS of cas: 2854-32-2, the publication is Bioorganic & Medicinal Chemistry Letters (1996), 6(19), 2263-2268, database is CAplus.

Indoles, e.g. I (R¹ = morpholino, morpholinocarbonyl, CO₂Me, CO₂H, morpholinomethyl; R² = 2-, 4-ClC₆H₄, 1-, 2-naphthyl, etc.), were prepared as potent ligands for the human peripheral cannabinoid (hCB₂) receptor. Two of these indole analogs exhibited nanomolar potencies (K_i) with good selectivity for the hCB₂ receptor over the human central cannabinoid (hCB₁) receptor.

Bioorganic & Medicinal Chemistry 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, SDS of cas: 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

Nycholat, Corwin M. published the artcileA sulfonamide sialoside analogue for targeting Siglec-8 and -F on immune cells, Synthetic Route of 166883-20-1, the publication is Journal of the American Chemical Society (2019), 141(36), 14032-14037, database is CAplus and MEDLINE.

The Siglec family of cell surface receptors have emerged as attractive targets for cell-directed therapies due to their restricted expression on immune cells, endocytic properties, and ability to modulate receptor signaling. Human Siglec-8, for instance, has been identified as a therapeutic target for the treatment of eosinophil and mast cell disorders. A promising strategy to target Siglecs involves the use of liposomal nanoparticles with a multivalent display of Siglec ligands. A key challenge for this approach is the identification of a high affinity ligand for the target Siglec. Here, we report the development of a ligand of Siglec-8 and its closest murine functional orthologue Siglec-F that is capable of targeting liposomes to cells expressing Siglec-8 or -F. A glycan microarray library of synthetic 9-N-sulfonyl sialoside analogs was screened to identify potential lead compounds The best ligand, 9-N-(2-naphthyl-sulfonyl)-Neu5Acα2-3-[6-O-sulfo]-Galβ1-4GlcNAc (6′-O-sulfo ^NSANeu5Ac) combined the lead 2-naphthyl sulfonyl C-9 substituent with the preferred sulfated scaffold. The ligand 6′-O-sulfo ^NSANeu5Ac was conjugated to lipids for display on liposomes to evaluate targeted delivery to cells. Targeted liposomes showed strong in vitro binding/uptake and selectivity to cells expressing Siglec-8 or -F and, when administered to mice, exhibit in vivo targeting to Siglec-F⁺ eosinophils.

Journal of the American Chemical Society published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C9H8ClNO3S, Synthetic Route of 166883-20-1.

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

Donaldson, Robert M. Jr. published the artcileUrinary excretion of indolic compounds in rats with intestinal pouches, Application In Synthesis of 2642-37-7, the publication is American Journal of Physiology (1961), 794-6, database is CAplus and MEDLINE.

The urinary excretion of indican and free and total indoleacetic acid is significantly increased in the rat in the presence of a localized area of intestinal stasis produced surgically by the creation of a pouch in the small intestine. Tryptamine, serotonin, and 5-hydroxyindoleacetic acid excretion in the urine is not altered. Intestinal stasis and bacterial activity within the pouch are responsible for the increased amounts of indican and indoleacetic acid in the urine.

American Journal of Physiology 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, Application In Synthesis of 2642-37-7.

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

Sadaie, Mahito published the artcileCell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition, COA of Formula: C19H21N3O3S, the publication is Molecular Biology of the Cell (2015), 26(17), 2971-2985, database is CAplus and MEDLINE.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides addnl. justification for AURKB as a cancer therapeutic target.

Molecular Biology of the Cell 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, COA of 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

Achab, Said published the artcileA short route to functionalized imidazo[4,5-c]carbazoles. Synthesis of the first example of the imidazo[4,5-c]β-carboline ring system, Product Details of C15H14BNO4S, the publication is Tetrahedron Letters (2001), 42(50), 8825-8828, database is CAplus.

A new synthetic route to the functionalized imidazo[4,5-c]carbazole I, via intramol. electrocyclization of the vinylimidazolylindole II is described. Thermally induced ring-closure of the (4-amino-5-imidazolyl)-3-indolecarboxylate III led to the previously unknown imidazo[4,5-c]-β-carboline ring system IV. These heterocycles were efficiently converted into analogs of both the marine cytotoxic agents grossularines-1 and -2 and the antimicrobial alkaloid eudistomin U.

Tetrahedron Letters 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, Product Details of 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

Shreevatsa, Bhargav published the artcileVirtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy, Application of 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is Molecules (2021), 26(22), 6863, database is CAplus and MEDLINE.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous FAD-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaroms., and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chem. classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of -8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

Molecules 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 C28H41N2P, Application of 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione.

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

Chen, Junjun published the artcileSelective and Cell-Active Inhibitors of the USP1/ UAF1 Deubiquitinase Complex Reverse Cisplatin Resistance in Non-small Cell Lung Cancer Cells, Related Products of indole-building-block, the publication is Chemistry & Biology (Cambridge, MA, United States) (2011), 18(11), 1390-1400, database is CAplus and MEDLINE.

Summary: Ubiquitin-specific proteases (USPs) have in recent years emerged as a promising therapeutic target class. We identified selective small-mol. inhibitors against a deubiquitinase complex, the human USP1/UAF1, through quant. high throughput screening (qHTS) of a collection of bioactive mols. The top inhibitors, pimozide and GW7647, inhibited USP1/UAF1 noncompetitively with a K _i of 0.5 and 0.7 μM, resp., and displayed selectivity against a number of deubiquitinases, deSUMOylase, and cysteine proteases. The USP1/UAF1 inhibitors act synergistically with cisplatin in inhibiting cisplatin-resistant non-small cell lung cancer (NSCLC) cell proliferation. USP1/UAF1 represents a promising target for drug intervention because of its involvement in translesion synthesis and Fanconi anemia pathway important for normal DNA damage response. Our results support USP1/UAF1 as a potential therapeutic target and provide an example of targeting the USP/WD40 repeat protein complex for inhibitor discovery.

Chemistry & Biology (Cambridge, MA, United States) 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, Related Products of 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