Month: November 2022

Zhang, Zhenzhou; Tang, Jianqiong; Song, Jiawei; Xie, Mengshi; Liu, Ying; Dong, Zhaojie; Liu, Xiaoyan; Li, Xueting; Zhang, Miwen; Chen, Yihang; Shi, Hongyu; Zhong, Jiuchang published the artcile< Elabela alleviates ferroptosis, myocardial remodeling, fibrosis and heart dysfunction in hypertensive mice by modulating the IL-6/STAT3/GPX4 signaling>, Synthetic Route of 347174-05-4, the main research area is elabela gene transcription ferroptosis heart fibrosis dysfunction hypertension mouse; IL6 STAT3 GPX4 signaling elabela drug target; Cardiac microvascular endothelial cells; Elabela; Ferroptosis; Hypertension; Myocardial remodeling.

Hypertension-mediated pathol. cardiac remodeling often progresses to heart failure. Elabela, mainly expressed in the cardiac microvascular endothelial cells (CMVECs), functions as a new endogenous ligand for apelin receptor. However, the exact roles of elabela in hypertension remain largely unclear. In this study, 10-wk-old male C57BL/6 mice were randomly subjected to infusion of angiotensin (Ang) II (1.5 mg/kg/d) or saline for 2 wk. Ang II infusion led to marked increases in systolic blood pressure levels and reduction of elabela levels in hypertensive mice with augmented myocardial hypertrophy and fibrosis. Furthermore, administration of elabela or ferroptosis inhibitor ferrostatin-1 significantly prevented Ang II-mediated pathol. myocardial remodeling, dysfunction, and ultrastructural injury in hypertensive mice with downregulated expression of inflammation-, hypertrophy-, and fibrosis-related genes. Notably, elabela strikingly alleviated Ang II-induced upregulation of iron levels and lipid peroxidation in hypertensive mice by suppressing cardiac interleukin-6 (IL-6)/STAT3 signaling and activating the xCT/glutathione peroxidase (GPX4) signaling. In cultured CMVECs, exposure to Ang II resulted in a marked decrease in elabela levels and obvious increases in cellular ferroptosis, proliferation, inflammation, and superoxide production, which were rescued by elabela or ferrostatin-1 while were blocked by co-treatment with rhIL-6. Furthermore, knockdown of elabela by siRNA in CMVECs contributed to Ang II-mediated augmentations in cellular proliferation, migration, and oxidative stress in cultured cardiac fibroblasts and cardiomyocytes, resp. In conclusion, elabela antagonizes Ang II-mediated promotion of CMVECs ferroptosis, adverse myocardial remodeling, fibrosis and heart dysfunction through modulating the IL-6/STAT3/GPX4 signaling pathway. Targeting elabela-APJ axis serves as a novel strategy for hypertensive heart diseases.

Free Radical Biology & Medicine published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (ANP). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Synthetic Route of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Brown, Herbert C.; Okamoto, Y.; Ham, Geo. published the artcile< Rates of solvolysis of the halophenyldimethylcarbinyl chlorides. The effect of halogen substituents upon the rates of electrophilic reactions>, Electric Literature of 112-63-0, the main research area is .

A series of Et halobenzoates, XC6H4CO2Et, was prepared from the free acids by standard esterification methods in approx. 90% yield (X, b.p./mm., nD20, and m.p. of free acid given): o-F, 85.5°/8, 1.4920, 128°; m-F, 84°/9.2, 1.4848, 124.5; p-F, 87.5°/11, 1.4860, 183.5°; p-Cl, 65°/1, 1.5239, 240.5°; o-Br, 135°/15, 1.5436, 150°; m-Br, 131°/17, 1.5428, 154°; p-Br, 129°/15, 1.5460, 255; m-I, 114°/2.1, 1.5830, 187°; p-I, 126.5°/4, 1.5877, 268°. Similarly were prepared the following esters XC6H4CO2Me (same data given): o-Cl, 99°/8.5, -, 141°; m-Cl, 106°/13, -, 154.5°; p-Cl, 112.5°/8, -, 240.5°; o-I, 103.5°/1, 1.6052, 163°. The appropriate ester (0.25 mole) in 150 cc. Et2O added to 0.55 mole MeMgI in 200 cc. Et2O, the mixture decomposed with saturated aqueous NH4Cl and ice, and the Et2O layer worked up gave 70-5% of the corresponding compounds XC6H4C(OH)Me2 (I) (X, b.p./mm., m.p., and nD20 given): o-F, 74.8°/8, 29.30°, -; m-F, 87°/7, -, 1.4995; p-F, 86°/8.2, 37.8, -; o-Cl, 79.2°/2.2, 23.7, 1.5416; m-Cl, 88.0°/2.2, -, 1.5370; p-Cl, 92.5°/3, 43.3, -; o-Br, 112°/5.2, -, 1.5634; m-Br, 104.5°/3.2, -, 1.5602; p-Br, -, 45.6°, -; o-I, 121°/5.5, -, 1.6017; m-I, -, 59-61°, -; p-I, -, 57-7.5°, -. The appropriate I (5 g.) treated with dry HCl until the weight became constant, the lower layer withdrawn, and the upper layer treated with CaCl2 and evacuated gave the corresponding chlorides, XC6H4CClMe2 (II), which were used without further purification. Aqueous 90% Me2CO adjusted with minor amounts of H2O or Me2CO until Me2PhCCl yielded a rate constant identical with that obtained previously (preceding abstract), 100 cc. solvent treated with approx. 1 cc. of the appropriate II, a 5-cc. zero-time sample removed after 10 min., added to 100 cc. Me2CO at 0°, titrated immediately with 0.0305N NaOH and methyl red as the indicator, and 6-7 addnl. samples withdrawn at the appropriate time intervals and titrated gave the desired rate data for the solvolysis of the II (X, rate constants k1 × 105 sec.-1 at 25°, 40, and 55°, relative ratio at 25°, Eact., ΔH++, and ΔS++ given): H, 12.4, -, – (0.600 at 0° and 36.1 at 35°), 1.00, 19.5, 18.8, -12.5; o-F, 0.622, 3.44, 15.8, 0.0502, 20.9, 20.3, -14.4; o-Cl, 0.0975, 0.625, 3.39, 0.00786, 23.0, 22.3, -11.1; o-Br, 0.0753, 0.517, 2.67, 0.00606, 23.1, 22.5, -11.1; o-I, 0.137, 0.839, 4.56, 0.0110, 22.7, 22.1, -11.4; m-F, 0.311, 1.65, 7.39, 0.0251, 20.5, 19.9, -17.0; m-Cl, 0.194, 1.13, 5.25, 0.0156, 21.3, 20.7, -15.1; m-Br, 0.178, 1.06, 5.44, 0.0144, 22.1, 21.5, -12.7; m-I, 0.289, 1.59, 7.22, 0.0233, 20.8, 20.2, -16.1; p-F, 26.5, -, – (1.32 at 0°, 8.44 at 15°), 2.14, 19.4, 18.8, -11.7; p-Cl, 3.78, 18.1, – (0.163 at 0°), 0.305, 20.0, 19.5, -13.6; p-Br, 2.58, -, – (7.83 at 35°, 21.2 at 45°), 0.208, 19.9, 19.2, -15.2; p-I, 3.03, -, – (9.00 at 35°, 24.0 at 45°), 0.244, 19.5, 18.8, -16.0. Within each of the 3 isomeric series, the observed order of reactivity is F > Cl > Br < I. The observed magnitudes of the rate constants, together with the observed reactivity orders, can be rationalized in terms of inductive effect, resonance, and steric inhibition of resonance. Journal of the American Chemical Society published new progress about Halogens. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Electric Literature of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Huang, Guang; Murillo Solano, Claribel; Melendez, Joel; Shaw, Justin; Collins, Jennifer; Banks, Robert; Arshadi, Arash Keshavarzi; Boonhok, Rachasak; Min, Hui; Miao, Jun; Chakrabarti, Debopam; Yuan, Yu published the artcile< Synthesis, Structure-Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines>, COA of Formula: C19H34O2, the main research area is arylvinylquinoline chloro preparation antimalarial activity.

There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clin. cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound To optimize UCF501, we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a Plasmodium falciparum CQ-resistant Dd2 strain, with excellent selectivity profiles (resistance index < 1 and selectivity index > 200). Several metabolically stable 2-arylvinylquinolines are identified as fast-acting agents that kill asexual blood-stage parasites at the trophozoite phase, and the most promising compound I also demonstrates transmission blocking potential. Addnl., the monophosphate salt of I exhibits excellent in vivo antimalarial efficacy in the murine model without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of antimalarial drug leads.

Journal of Medicinal Chemistry published new progress about Antimalarials. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, COA of Formula: C19H34O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Huang, Kuan-Wei; Hsu, Kai-Cheng; Chu, Lee-Ya; Yang, Jinn-Moon; Yuan, Hanna S.; Hsiao, Yu-Yuan published the artcile< Identification of Inhibitors for the DEDDh Family of Exonucleases and a Unique Inhibition Mechanism by Crystal Structure Analysis of CRN-4 Bound with 2-Morpholin-4-ylethanesulfonate (MES)>, Electric Literature of 112-63-0, the main research area is DEDDh exonuclease inhibitor identification; RNase T inhibitor identification; crystal structure exonuclease CRN4 MES complex; Lassa virus NP exonuclease inhibitor identification.

The DEDDh family of 3’→5′-exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here, using RNase T and CRN-4 exonuclease as the model systems, the authors identified potential inhibitors for DEDDh exonucleases. The authors further showed that 2 of the inhibitors (ATA and PV6R) indeed inhibited the exonuclease activity of the viral protein, NP exonuclease of Lassa fever virus in vitro. Moreover, the authors determined the crystal structure of CRN-4 in complex with MES that revealed a unique inhibition mechanism by inducing the general base His-179 to shift out of the active site. These results not only provided the structural basis for the inhibition mechanism but also suggested potential lead inhibitors for DEDDh exonucleases that may pave the way for designing nuclease inhibitors for biochem. and biomedical applications.

Journal of Medicinal Chemistry published new progress about Crystal growth. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Electric Literature of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zhdankin, Viktor V.; Persichini, P. J. III; Zhang, Lu; Fix, Shannon; Kiprof, Paul published the artcile< Synthesis and structure of benzoboroxoles: novel organoboron heterocycles>, Product Details of C19H34O2, the main research area is crystal structure benzoxaborole dihydro hydroxy; mol structure benzoxaborole dihydro hydroxy; benzoxaborole dihydro hydroxy preparation structure substitution reaction; heterocyclic compound oxygen boron preparation structure reactivity theor calculation; borate cyclization lithiated benzyl alc; Ab initio MO calculation benzoxaborole; Hartree Fock MP2 B3LYP density functional theory benzoxaborole structure; hydrogen bond intermol cyclic oxygen hydroxy hydrogen benzoxaborole.

Benzoxaboroles (I) (R = H, CH3, CF3) were prepared from the readily available o-bromobenzyl or o-iodobenzyl alcs. via dilithiation followed by reaction with triisopropyl borate. X-ray structural anal. of 1-hydroxy-1,3-dihydro-2,1-benzoxaborole as well as the results of ab initio MO calculations indicated a planar structure of the boron center with a relatively short C-B bond. Preliminary results regarding the chem. of benzoxaboroles were also reported.

Tetrahedron Letters published new progress about Crystal structure. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Lin; Xing, Xi; Zeng, Xianfeng; Jackson, S. RaElle; TeSlaa, Tara; Al-Dalahmah, Osama; Samarah, Laith Z.; Goodwin, Katharine; Yang, Lifeng; McReynolds, Melanie R.; Li, Xiaoxuan; Wolff, Jeremy J.; Rabinowitz, Joshua D.; Davidson, Shawn M. published the artcile< Spatially resolved isotope tracing reveals tissue metabolic activity>, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is infusion nutrient isotope 3hydroxybutyrate hippocampus midbrain medulla thalamus metabolism.

Isotope tracing has helped to determine the metabolic activities of organs. Method to probe metabolic heterogeneity within organs are less developed. We couple stable-isotope-labeled nutrient infusion to matrix-assisted laser desorption ionization imaging mass spectrometry (iso-imaging) to quantitate metabolic activity in mammalian tissues in a spatially resolved manner. In the kidney, we visualize gluconeogenic flux and glycolytic flux in the cortex and medulla, resp. Tricarboxylic acid cycle substrate usage differs across kidney regions; glutamine and citrate are used preferentially in the cortex and fatty acids are used in the medulla. In the brain, we observe spatial gradations in carbon inputs to the tricarboxylic acid cycle and glutamate under a ketogenic diet. In a carbohydrate-rich diet, glucose predominates throughout but in a ketogenic diet, 3-hydroxybutyrate contributes most strongly in the hippocampus and least in the midbrain. Brain nitrogen sources also vary spatially; branched-chain amino acids contribute most in the midbrain, whereas ammonia contributes in the thalamus. Thus, iso-imaging can reveal the spatial organization of metabolic activity.

Nature Methods published new progress about Amino acid metabolism disorders. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Nykaza, Trevor V.; Li, Gen; Yang, Junyu; Luzung, Michael R.; Radosevich, Alexander T. published the artcile< PIII/PV=O Catalyzed Cascade Synthesis of N-Functionalized Azaheterocycles>, Application In Synthesis of 30095-98-8, the main research area is azaheterocycle preparation organophosphorus catalyst cascade; cross-coupling; cyclization; nitrogen heterocycles; organocatalysis; phosphorus.

An organocatalytic method for the modular synthesis of diverse N-aryl and N-alkyl azaheterocycles (indoles, oxindoles, benzimidazoles, and quinoxalinediones) is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) and a hydrosilane reductant to drive the conversion of ortho-functionalized nitroarenes into azaheterocycles through sequential intermol. reductive C-N cross coupling with boronic acids, followed by intramol. cyclization. This method enables the rapid construction of azaheterocycles from readily available building blocks, including a regiospecific approach to N-substituted benzimidazoles and quinoxalinediones.

Angewandte Chemie, International Edition published new progress about Aromatic nitro compounds Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (o-acylamino). 30095-98-8 belongs to class esters-buliding-blocks, and the molecular formula is C9H9NO4, Application In Synthesis of 30095-98-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Bamborough, Paul; Barnett, Heather A.; Becher, Isabelle; Bird, Mark J.; Chung, Chun-wa; Craggs, Peter D.; Demont, Emmanuel H.; Diallo, Hawa; Fallon, David J.; Gordon, Laurie J.; Grandi, Paola; Hobbs, Clare I.; Hooper-Greenhill, Edward; Jones, Emma J.; Law, Robert P.; Le Gall, Armelle; Lugo, David; Michon, Anne-Marie; Mitchell, Darren J.; Prinjha, Rab K.; Sheppard, Robert J.; Watson, Allan J. B.; Watson, Robert J. published the artcile< GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain>, HPLC of Formula: 112-63-0, the main research area is GSK6853 inhibitor BRPF1 bromodomain; BET; BRD1; BRPF1; BRPF2; BRPF3; bromodomain; chemical probe; epigenetics; inhibitor.

The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micromolar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents (potential as). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, HPLC of Formula: 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Ji, Na; Liu, Zhenyu; Diao, Xinyong; Bao, Jinrong; Yu, Zhihao; Song, Chunfeng; Liu, Qingling; Ma, Degang; Lu, Xuebin published the artcile< A novel Ni/AC catalyst prepared by MOCVD method for hydrogenation of ethyl levulinate to γ-valerolactone>, Category: esters-buliding-blocks, the main research area is nickel catalyst prepared vapor deposition ethyl levulinate hydrogenation valerolactone.

GVL (γ-valerolactone) is identified as an important biomass platform mol. due to its wide application. In this work, a series of novel supported Ni catalysts with different supports and Ni loading were synthesized via metal-organic chem. vapor deposition (MOCVD) method for the hydrogenation of EL (Et levulinate) to GVL. Fourier transform IR spectroscopy, X-ray powder diffraction, nitrogen adsorption/desorption, inductively coupled plasma optical emission spectroscopy and transmission electron microscopy were used to characterize the as-synthesized catalysts. The results showed that the 2 weight% Ni/AC(MOCVD) presented superior catalytic activity when compared with the catalyst prepared by impregnation method. This behavior is explained in terms of the smaller Ni nanoparticles (4.28 nm) and higher dispersion on 2 weight% Ni/AC(MOCVD). Among the catalysts, the 2 weight% Ni/AC catalyst exhibited the best catalytic performance with 99.7% EL conversion and 79.8% GVL yield under 1 MPa initial H2 pressure (measured at room temperature) at 250°C for 2 h. In addition, the reaction conditions were optimized and the stability of the catalyst were also investigated. The insights gained from this study in the design of high dispersed Ni particles with smaller particle size via MOCVD method will facilitate the metal-catalyzed hydrogenation of EL to GVL.

Molecular Catalysis published new progress about Adsorption. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Le Rhun, Emilie; Oppong, Felix Boakye; Vanlancker, Maureen; Stupp, Roger; Nabors, Burt; Chinot, Olivier; Wick, Wolfgang; Preusser, Matthias; Gorlia, Thierry; Weller, Michael published the artcile< Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma.>, Computed Properties of 112-63-0, the main research area is anemia; chemoradiotherapy; lymphopenia; neutropenia; progression; survival; temozolomide; thrombocytopenia.

BACKGROUND: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. METHODS: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, and lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark Cox model was used. For each primary association analysis, a significance level of 1.7% was used. RESULTS: Lower neutrophil counts at baseline were associated with better PFS (P = .011) and OS (P < .001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (P = .009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58-1.06), whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75-1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62-0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46-0.92) was associated with superior OS (P = .013), but not PFS. CONCLUSIONS: The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma. Neuro-oncology published new progress about 112-63-0. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Computed Properties of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics