Month: November 2022

Spangler, Jillian E. published the artcileα-Arylation of Saturated Azacycles and N-Methylamines via Palladium(II)-Catalyzed C(sp³)-H Coupling, COA of Formula: C14H12BNO4S, the publication is Journal of the American Chemical Society (2015), 137(37), 11876-11879, database is CAplus and MEDLINE.

In the presence of Pd(O₂CCF₃)₂, N-(thiopivaloyl) nitrogen heterocycles such as I (R = H; X = CH₂, CH₂CH₂CH₂) underwent chemoselective and regioselective arylation with arylboronic acids R¹B(OH)₂ (R¹ = Ph, 2-MeC₆H₄, 3-MeC₆H₄, 4-MeC₆H₄, 3-MeOC₆H₄, 4-MeOC₆H₄, 4-AcNHC₆H₄, 4-F₃COC₆H₄, 3,4-Cl₂C₆H₃, 4-ClC₆H₄, 3-ClC₆H₄, 2-FC₆H₄, 4-FC₆H₄, 4-F₃CC₆H₄, 4-AcC₆H₄, 3-AcC₆H₄, 5-benzofuranyl, 1-PhSO₂-4-indolyl, 1-PhSO₂-5-indolyl, 6-F-3-pyridinyl, 2-F-4-pyridinyl, 6-Cl-3-pyridinyl, 6-MeO-3-pyridinyl, 2-MeO-4-pyridinyl) mediated by 1,4-benzoquinone in tert-amyl alc. with KHCO₃ to give monoarylated heterocycles such as (thiopivaloyl)arylpyrrolidines I (R = R¹; R¹ = Ph, 2-MeC₆H₄, 3-MeC₆H₄, 4-MeC₆H₄, 3-MeOC₆H₄, 4-MeOC₆H₄, 4-AcNHC₆H₄, 4-F₃COC₆H₄, 3,4-Cl₂C₆H₃, 4-ClC₆H₄, 3-ClC₆H₄, 2-FC₆H₄, 4-FC₆H₄, 4-F₃CC₆H₄, 4-AcC₆H₄, 3-AcC₆H₄, 5-benzofuranyl, 1-PhSO₂-4-indolyl, 1-PhSO₂-5-indolyl, 6-F-3-pyridinyl, 2-F-4-pyridinyl, 6-Cl-3-pyridinyl, 6-MeO-3-pyridinyl, 2-MeO-4-pyridinyl; X = CH₂) and (thiopivaloyl)phenylhexahydroazepine I (R = Ph; X = CH₂CH₂CH₂). Unsym. trans-2,5-diaryl-1-(thiopivaloyl)pyrrolidines were prepared in >20:1 dr in one pot using this method. Tertiary N-methylthiopivalamides t-BuC(:S)N(Me)R² (R² = Me, n-Pr, PhCH₂, PhCH₂CH₂, cyclohexyl, Ph, 4-FC₆H₄, 4-ClC₆H₄) underwent chemoselective and regioselective arylation with arylboronic acids (R³ = Ph, 1-PhSO₂-5-indolyl, 5-benzofuranyl, 6-MeO-3-pyridinyl) under similar conditions to yield (arylmethyl)thiopivalamides t-BuC(:S)N(CH₂R³)R² (R² = Me, n-Pr, PhCH₂, PhCH₂CH₂, cyclohexyl, Ph, 4-FC₆H₄, 4-ClC₆H₄; R³ = Ph, 1-PhSO₂-5-indolyl, 5-benzofuranyl, 6-MeO-3-pyridinyl). The structure of a trans-(fluorophenyl)(methoxyphenyl)thiopivaloylpyrrolidine was determined by X-ray crystallog.

Journal of the American Chemical Society published new progress about 480438-51-5. 480438-51-5 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-(Phenylsulfonyl)-1H-indol-5-yl)boronic acid, and the molecular formula is C6H3ClFNO2, COA of Formula: C14H12BNO4S.

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

Walpole, C. published the artcile2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (SDZ NKT 343), a Potent Human NK₁ Tachykinin Receptor Antagonist with Good Oral Analgesic Activity in Chronic Pain Models, Application In Synthesis of 167015-84-1, the publication is Journal of Medicinal Chemistry (1998), 41(17), 3159-3173, database is CAplus and MEDLINE.

A lead compound which had sub-micromolar affinity for the rabbit NK₁ receptor but negligible affinity for rat NK₁ receptors, 2-MeOC₆H₄CH₂NHCS-Pro-NHCHPh₂, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK₁ selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK₁ receptor which arose from this series, I, combined a 2-chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO₂ phenylthiourea analogs which led directly to the analogous urea, II (SDZ NKT 343), a highly potent ligand for the human NK₁ receptor (K_i = 0.16 nM). In addition to its high in vitro potency, II proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clin. evaluation of II as a novel analgesic agent is currently underway.

Journal of Medicinal Chemistry 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 C4H6BrFO2, 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

Paveliev, Mikhail published the artcileAcute brain trauma in mice followed by longitudinal two-photon imaging, Synthetic Route of 330161-87-0, the publication is Journal of Visualized Experiments (2014), e51559/1-e51559/8, database is CAplus and MEDLINE.

Although acute brain trauma often results from head damage in different accidents and affects a substantial fraction of the population, there is no effective treatment for it yet. Limitations of currently used animal models impede understanding of the pathol. mechanism. Multiphoton microscopy allows studying cells and tissues within intact animal brains longitudinally under physiol. and pathol. conditions. Here, we describe two models of acute brain injury studied by means of two-photon imaging of brain cell behavior under posttraumatic conditions. A selected brain region is injured with a sharp needle to produce a trauma of a controlled width and depth in the brain parenchyma. Our method uses stereotaxic prick with a syringe needle, which can be combined with simultaneous drug application. We propose that this method can be used as an advanced tool to study cellular mechanisms of pathophysiol. consequences of acute trauma in mammalian brain in vivo. In this video, we combine acute brain injury with two preparations: cranial window and skull thinning. We also discuss advantages and limitations of both preparations for multisession imaging of brain regeneration after trauma.

Journal of Visualized Experiments 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, Synthetic Route 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

Morgan, Amanda J. published the artcileDetection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain, Recommanded Product: 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, the publication is ACS Chemical Neuroscience (2018), 9(7), 1552-1559, database is CAplus and MEDLINE.

Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with the lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacol. inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiol. functions of PG-Gs.

ACS Chemical Neuroscience 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, Recommanded Product: 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

Grover, Huck K. published the artcileThe Synthesis of 5,5-Disubstituted Piperidinones via a Reductive Amination-Lactamization Sequence: The Formal Synthesis of (±)-Quebrachamine, COA of Formula: C15H20N2O2, the publication is Synlett (2015), 26(6), 815-819, database is CAplus.

A preliminary investigation into the prospect of a common synthetic intermediate for the synthesis of a variety of indole alkaloids has led to a synthesis of substituted piperidinones and the corresponding piperidines. These common natural product cores are accessed via a reductive amination-lactamization sequence of di-Me 3-ethyl-3-formylpimelate. The synthetic utility of this initial study has been displayed in the formal synthesis of (±)-quebrachamine.

Synlett 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, COA of Formula: C15H20N2O2.

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

Yu, Shun published the artcileStability of human serum albumin structure upon toxin uptake explored by small angle neutron scattering, COA of Formula: C8H6KNO4S, the publication is Polymer (2018), 175-183, database is CAplus.

The possible denaturation or tertiary structural changes of human serum albumin (HSA) upon adsorption of uremic toxin was investigated using small-angle neutron scattering (SANS). Calorimetric data in previous studies provided proof of binding between HSA and 2 classes of uremic toxins: (1) small-mol.-weight (SMW) toxins and (2) middle-mol.-weight (MMW) toxins. Polyacrylic acid, a representative polyelectrolyte of neg. net charge, was used as a model MMW toxin and 2 mols. [phenylacetic acid (PhAA) and indoxyl sulfate (IDS)] represented the SMW toxins. The present study found no proof of destabilization of the protein structure upon toxin uptake. Analyzing the structure factor of scattering intensities from high concentrated protein samples complexed with PhAA and IDS showed that interaction between native and complexed HSA was also not altered. However, a small effect of the net charge of HSA was found in the case of urea-modified proteins.

Polymer 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 C11H15BFNO4, COA of Formula: C8H6KNO4S.

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

Li, Jason Z. published the artcileMechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent, COA of Formula: C18H16N2O6, the publication is Toxicology and Applied Pharmacology (2014), 281(3), 285-293, database is CAplus and MEDLINE.

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clin. trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and ESR (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16-F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16-F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16-F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells.

Toxicology and Applied Pharmacology 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, COA of Formula: C18H16N2O6.

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

Zhou, Mingwei published the artcileZinc triflate-mediated cyclopropanation of oxindoles with vinyl diphenyl sulfonium triflate: a mild reaction with broad functional group compatibility, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one, the publication is RSC Advances (2017), 7(7), 3741-3745, database is CAplus.

The first use of zinc triflate for the cyclopropanation of unprotected oxindoles with vinyl di-Ph sulfonium triflate salt to afford spiro[cyclopropane-1,3′-indoline]-2′-ones I [R = 5-OH, 6-F, 7-Cl, 4-Br, etc.] was reported. The reaction proceeded under ambient conditions and consistently provided high yields with broad functional group tolerability. The utility for the late-stage functionalization (LSF) of complex mols. was demonstrated.

RSC Advances 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 C15H14Cl2S2, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one.

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

Taddeini, L. published the artcileInhibition of the Ehrlich reaction of porphobilinogen by indican and related compounds, Safety of Potassium 1H-indol-3-yl sulfate, the publication is Clinica Chimica Acta (1962), 890-1, database is CAplus and MEDLINE.

From a study of the Ehrlich reaction of porphobilinogen (I) and related compounds, it was found that K indoxylsulfate (urinary indican) as well as certain other members of the indole series are markedly inhibitory. Because of the importance of this finding for detection of I in the urine, a study on the inhibitory effect of indican was made. The results revealed an inhibitory effect of indican on the I aldehyde color intensity, increasing from about 35% at a concentration of indican of 0.625 × 10^-4 millimole/ml. to over 85% at a concentration of 2.50 × 10^-4. Complete inhibition of the I aldehyde color reaction was obtained with an indican concentration of 5.00 × 10^-4. Indole and 5-hydroxyindoleacetic acid (II) are also inhibitory to about the same degree as indican. The inhibition was not due to complexing of indoles with I since the addition of the indole to the fully developed solution of the I-aldehyde compound also produced rapid fading of the color. The mechanism responsible for the inhibition is the nucleophilic addition of indoles to the I-aldehyde compound This yields a colorless intermediary, p-dimethylaminophenylpyrrylindolylmethane. Indican inhibits the Ehrlich reaction of opsopyrroledicarboxylic acid (III) to a lesser extent (35% as compared with 86% in a 2:1 molar ratio), and II has essentially no inhibitory effect under the same conditions. III is structurally similar to I except in lacking the α-aminomethyl group of the latter compound The much smaller inhibition of III thus suggests that the α-aminomethyl group (which is protonated in the presence of the Ehrlich reagent), activated the I-aldehyde compound with respect to nucleophilic attack of the indole. However, indole itself inhibits the aldehyde reaction of III to at least 95%, in a 2:1 molar ratio. Thus, it is evident that the character of the substituents of the indole is also a factor of importance. The present observations on the inhibition of the I-Ehrlich reaction by indican and other indolic compounds clarify the recent finding that an unknown inhibitor is present in some I-containing urines responsible for false neg. Ehrlich reactions.

Clinica Chimica Acta 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 C7H5ClN2S, Safety of Potassium 1H-indol-3-yl sulfate.

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

Parrish, Jay P. published the artcileEstablishment of substituent effects in the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065, SDS of cas: 796870-32-1, the publication is Bioorganic & Medicinal Chemistry (2003), 11(17), 3815-3838, database is CAplus and MEDLINE.

An extensive series of CBI analogs of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be ≥1000-fold providing simplified analogs containing a single DNA binding subunit that are more potent (IC₅₀=2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065.

Bioorganic & Medicinal Chemistry published new progress about 796870-32-1. 796870-32-1 belongs to indole-building-block, auxiliary class Indols, name is 7-Cyano-1H-indole-2-carboxylic acid, and the molecular formula is C10H6N2O2, SDS of cas: 796870-32-1.

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