Month: November 2022

Biswas, Subhasish published the artcileOne-Step Synthesis of 2-Amino-5H-pyrimido[5,4-b]indoles, Substituted 2-(1,3,5-triazin-2-yl)-1H-indoles, and 1,3,5-Triazines from Aldehydes, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde, the publication is European Journal of Organic Chemistry (2012), 2012(18), 3492-3499, S3492/1-S3492/20, database is CAplus.

An efficient one-step synthesis of 2-amino-5H-pyrimido[5,4-b]indoles through a copper-catalyzed cascade reaction between 3-haloindole-2-carbaldehydes and guanidine hydrochloride is described. In contrast, the base-mediated reactions of either 3-haloindole-2-carbaldehydes or substituted indole-2-carbaldehydes with substituted amidine hydrochlorides in DMSO result in the formation of 2-(1,3,5-triazin-2-yl)-1H-indole derivatives in one step in excellent yields. Studies toward exploring the utility of the method demonstrate that even substituted benzaldehydes undergo a similar reaction to efficiently yield 2,4,6-trisubstituted 1,3,5-triazines. A plausible mechanism for the formation of substituted 1,3,5-triazines identifies the role of DMSO as an oxidant during the reaction.

European Journal of Organic Chemistry 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, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde.

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

Godwin, Colin D. published the artcileThe Bruton′s tyrosine kinase inhibitor ibrutinib abrogates bispecific antibody-mediated T-cell cytotoxicity, Application of SU6656, the publication is British Journal of Haematology (2020), 189(1), e9-e13, database is CAplus and MEDLINE.

This study examined the abrogation of bispecific antibody (BiAb)-mediated T-cell cytotoxicity by Bruton′s tyrosine kinase inhibitor (BTKi) ibrutinib. Results suggests that ibrutinib-mediated inhibition of BiAb-mediated cancer cell killing is due to an inhibitory effect on T-cell effector function rather than induction of leukemia cell resistance. Together, the studies indicate acute exposure to BTKi impairs T-cell activation and lysis of target cells upon treatment with CD3-directed BiAbs, at least partially due to effects that are independent of BTK inhibition. Further mechanistic studies will be necessary to identify which signaling pathways are involved in this inhibitory effect of BTKi.

British Journal of Haematology 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

Favalli, Nicholas published the artcileScreening of Three Transition Metal-Mediated Reactions Compatible with DNA-Encoded Chemical Libraries, Application of 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is Helvetica Chimica Acta (2019), 102(4), n/a, database is CAplus and MEDLINE.

The construction of DNA-encoded chem. libraries (DECLs) crucially relies on the availability of chem. reactions, which are DNA-compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium-catalyzed reactions (Suzuki cross-coupling, Sonogashira cross-coupling, and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.

Helvetica Chimica Acta 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, Application of 6-(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

Romagnoli, Romeo published the artcileDiscovery of 8-methoxypyrazino[1,2-a]indole as a new potent antiproliferative agent against human leukemia K562 cells. a structure-activity relationship study, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Letters in Drug Design & Discovery (2009), 6(4), 298-303, database is CAplus and MEDLINE.

Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacol. research. The indole nucleus, frequently encountered as a mol. fragment in natural products and pharmaceutically active compounds, was employed as the initial building block for the synthesis of a series of pyrazino[1,2-a]indoles 1a-k, variably substituted at the 6, 7, 8 and 9-positions. Compound 1e (I), bearing the methoxy group at the 8-position of the pyrazino[1,2-a]indole nucleus was identified as a novel potent antiproliferative agent against the human chronic myelogenous leukemia K562 cell line, but it was much less active against several other cancer cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 8- to the 7- or 6-position, to furnish compounds 1f and 1g, resp., yielded inactive compounds The anal. of structure-activity relationships observed in the series of investigated compounds may represent the basis for the design of more active mols.

Letters in Drug Design & Discovery 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, Name: Ethyl 7-methoxy-1H-indole-2-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

Miller, David D. published the artcile3,5-Disubstituted-indole-7-carboxamides: The discovery of a novel series of potent, selective inhibitors of IKK-β, COA of Formula: C9H6BrNO2, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(8), 2255-2258, database is CAplus and MEDLINE.

The discovery and hit-to-lead exploration of a novel series of selective IKK-β kinase inhibitors is described. The initial lead fragment 3 (I) was identified by pharmacophore-directed virtual screening. Homol. model-driven SAR exploration of the template led to potent inhibitors, such as 12 (II), which demonstrate efficacy in cellular assays and possess encouraging developability profiles.

Bioorganic & Medicinal Chemistry Letters published new progress about 860624-90-4. 860624-90-4 belongs to indole-building-block, auxiliary class Indole,Bromide,Carboxylic acid,Indole, name is 5-Bromo-1H-indole-7-carboxylic acid, and the molecular formula is C9H6BrNO2, COA of Formula: C9H6BrNO2.

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

Trost, Barry M. published the artcileEnantioselective Divergent Synthesis of C19-Oxo Eburnane Alkaloids via Palladium-Catalyzed Asymmetric Allylic Alkylation of an N-Alkyl-α,β-unsaturated Lactam, Application In Synthesis of 167015-84-1, the publication is Journal of the American Chemical Society (2019), 141(12), 4811-4814, database is CAplus and MEDLINE.

The C19-oxo-functionalized eburnane alkaloids display a unique chem. structure and interesting biol. activity. Herein, we report a divergent enantioselective strategy to access these alkaloids by use of a challenging palladium-catalyzed asym. allylic alkylation of N-alkyl-α,β-unsaturated lactam I. 19-(S)-OH-Δ¹⁴-Vincamone (II, phutdonginin), (-)-19-OH-eburnamine (III), (+)-19-oxoeburnamine (IV), and (+)-19-OH-eburnamonine (V) have been concisely synthesized for the first time in 11 to 13 steps.

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 C22H18O2, Application In Synthesis of 167015-84-1.

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

Morounke, Saibu G. published the artcileGene expression modulation of apoptotic and oestrogen receptor alpha genes by active fractions of selected nigerian plants on cervical cancer cell line (HeLa), Synthetic Route of 192820-78-3, the publication is Tropical Journal of Natural Product Research (2021), 5(4), 772-777, database is CAplus.

The roles of natural product in drug discovery and development cannot be over emphasized. It plays a vital role in human therapy and gives a better understanding on the cellular pathways.This study investigated the modulatory effects of partially purified fractions of Piper guineense Schumach. & Thonn. (Piperaceae), Zanthoxylum zanthoxyloides Lam. (Rutaceae), Amaranthus viridis L. (Amaranthaceae), Costus afer Ker-Gawl. (Zingiberaceae) and Catharanthus roseus (L.) G. Don. (Apocynaceae) on estrogen receptor-α (ESR-α), tumor protein p53 (TP-53), retinoblastoma (RB) and NAD(P) H quinine oxidoreductase (NQO1) genes in cervical cancer cell line (HeLa cells). n-Hexane, ethylacetate, chloroform, and water fractions of 80% ethanol extracts of study plants were screened with brine shrimp lethality and water-soluble tetrazolium-1 (WST-1) cytotoxicity assay. HeLa cells were treated with 1:10 dilutions of IC₅₀ concentrations of test fractions for 24 h, total RNA was extracted, RNA quality was checked, and normalized to a baseline concentration Gene expression were monitored by semi-quant. reverse transcription-polymerase chain reaction (RT-PCR). Results showed that ESR-α was downregulated (p < 0.05) by P. guineense-hexane, C. roseus- chloroform and A. viridis-ethylacetate fractions. TP53 gene was up-regulated (p < 0.05) by P. guineense-hexane and Z. zanthoxyloides-ethylacetate fractions. None of the test fractions caused an up-regulation in the expression of retinoblastoma gene. NQO1 gene was down-regulated (p < 0.05) by C. roseus-chloroform, P. guineense-hexane, A. viridis, C. afer, and Z. zanthoxyloides ethylacetate fractions. Our study provides scientific evidence of the possible anti-proliferative potentials of C. roseus-chloroform, P. guineense-hexane, ethylacetate fractions of A. viridis, C.afer, and Z. zanthoxyloides in cervical cancer.

Tropical Journal of Natural Product Research 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

Roller, Devin G. published the artcileSynthetic Lethal Screening with Small-Molecule Inhibitors Provides a Pathway to Rational Combination Therapies for Melanoma, Computed Properties of 330161-87-0, the publication is Molecular Cancer Therapeutics (2012), 11(11), 2505-2515, database is CAplus and MEDLINE.

Recent data show that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways, suggesting that the inhibition of a single component of a canonical pathway is insufficient for the treatment of cancer. The biol. outcome of signaling through a network is inherently more robust and resistant to inhibition of a single network component. In this study, we conducted a functional chem. genetic screen to identify novel interactions between signaling inhibitors that would not be predicted on the basis of our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. The synergistic cytotoxicities identified did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. Among the most robust results was synergy between sorafenib, a multikinase inhibitor with activity against RAF, and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID). Drug substitution experiments using the NSAIDs celecoxib and ibuprofen or the MAP-ERK kinase inhibitor PD325901 and the RAF inhibitor RAF265 suggest that inhibition of COX and mitogen-activated protein kinase signaling are targets for the synergistic cytotoxicity of sorafenib and diclofenac. Cotreatment with sorafenib and diclofenac interrupts a pos. feedback signaling loop involving extracellular signal-regulated kinase, cellular phospholipase A2, and COX. Genome-wide expression profiling shows synergy-specific downregulation of survival-related genes. This study has uncovered novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially, depending on unexplored components of the cell genotype. Mol Cancer Ther; 11(11); 2505-15. ©2012 AACR.

Molecular Cancer Therapeutics 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

Alcaraz, Marie-Lyne published the artcileEfficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur, Formula: C9H8ClNO3S, the publication is Organic Process Research & Development (2005), 9(5), 555-569, database is CAplus.

The development of two efficient strategies for the synthesis of AZD4407 (I) is reported, both of which are considered suitable for large-scale manufacture In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4-one using Grignard chem. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulfur provides AZD4407 after acid-catalyzed deprotection and epimerization. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalyzed deprotection and epimerization.

Organic Process Research & Development 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, Formula: C9H8ClNO3S.

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

Narayana, B. published the artcileSimple syntheses of 5-fluoro/ chloro/ bromoindole-2-methanols and 5-fluoro/ chloro/ bromoindole-2-aldehydes, Quality Control of 220943-23-7, the publication is Organic Chemistry: An Indian Journal (2006), 2(1-3), 5-9, database is CAplus.

Efficient and simple methods for the syntheses of 5-haloindole-2-methanols and 5-haloindole-2-aldehydes have been described. 5-Haloindole-2-methanols were prepared by reduction of Me 5-haloindole-2-carboxylates with sodium borohydride in methanol/ THF media and 5-haloindole-2-aldehydes were prepared from the prepared 5-haloindole-2-methanols by oxidation with pyridinium chlorochromate or chromium trioxide-pyridine prepared in situ. The synthesized compounds were isolated in good yields and characterized by ¹H NMR, ¹³C NMR, FABMS and elemental anal.

Organic Chemistry: An Indian Journal 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, Quality Control of 220943-23-7.

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