Day: October 13, 2022

Jo, Hakryul; Patterson, Victoria; Stoessel, Sean; Kuan, Chia-Yi; Hoh, Josephine published the artcile< Protoporphyrins enhance oligomerization and enzymatic activity of HtrA1 serine protease>, Related Products of 163769-88-8, the main research area is protoporphyrin oligomerization HtrA1 serine protease protoporphyria hemin.

High temperature requirement protein A1 (HtrA1), a secreted serine protease of the HtrA family, is associated with a multitude of human diseases. However, the exact functions of HtrA1 in these diseases remain poorly understood. We seek to unravel the mechanisms of HtrA1 by elucidating its interactions with chem. or biol. modulators. To this end, we screened a small mol. library of 500 bioactive compounds to identify those that alter the formation of extracellular HtrA1 complexes in the cell culture medium. An initial characterization of two novel hits from this screen showed that protoporphyrin IX (PPP-IX), a precursor in the heme biosynthetic pathway, and its metalloporphyrin (MPP) derivatives fostered the oligomerization of HtrA1 by binding to the protease domain. As a result of the interaction with MPPs, the proteolytic activity of HtrA1 against Fibulin-5, a specific HtrA1 substrate in age-related macular degeneration (AMD), was increased. This phys. interaction could be abolished by the missense mutations of HtrA1 found in patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Furthermore, knockdown of HtrA1 attenuated apoptosis induced by PPP-IX. These results suggest that PPP-IX, or its derivatives, and HtrA1 may function as co-factors whereby porphyrins enhance oligomerization and the protease activity of HtrA1, while active HtrA1 elevates the pro-apoptotic actions of porphyrin derivatives Further anal. of this interplay may shed insights into the pathogenesis of diseases such as AMD, CARASIL and protoporphyria, as well as effective therapeutic development.

PLoS One published new progress about Age-related macular degeneration. 163769-88-8 belongs to class quinoxaline, and the molecular formula is C22H21N3O2, Related Products of 163769-88-8.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Lee, Hong Geun; Milner, Phillip J.; Placzek, Michael S.; Buchwald, Stephen L.; Hooker, Jacob M. published the artcile< Virtually Instantaneous, Room-Temperature [11C]-Cyanation Using Biaryl Phosphine Pd(0) Complexes>, Electric Literature of 23088-24-6, the main research area is cyanation carbon 11 aryl compound biaryl phosphine palladium catalyst; aryl nitrile carbon 11 labeled preparation.

A new radiosynthetic protocol for the preparation of [11C]aryl nitriles has been developed. This process is based on the direct reaction of in situ prepared L·Pd(Ar)X complexes (L = biaryl phosphine) with [11C]HCN. The strategy is operationally simple, exhibits a remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity compared to previously reported systems. With this procedure, a variety of [11C]nitrile-containing pharmaceuticals, e.g., [11C]citalopram, were prepared with high radiochem. efficiency.

Journal of the American Chemical Society published new progress about Aromatic nitriles Role: SPN (Synthetic Preparation), PREP (Preparation) ([11C]-labeled). 23088-24-6 belongs to class quinoxaline, and the molecular formula is C9H5N3, Electric Literature of 23088-24-6.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Xu, Xinyu; Chen, Kezhi published the artcile< Palladium-catalyzed C-H activation of anisole with electron-deficient auxiliary ligands: a mechanistic investigation>, Category: quinoxaline, the main research area is anisole iodobenzene arylation mechanism PES Hammett constant.

Palladium-catalyzed selective C-H activation-functionalization has shown its significance in organic transformations. Recently, Yu et al. reported a palladium-norbornene co-catalyzed meta-selective arylation of electron-rich arenes. Although the exptl. observed site-selectivity has been successfully explained by the computational work of Dongju Zhang and co-workers, some important exptl. factors, such as the ligand choice and narrow substrate scope, remain unrationalized. In contrast to what has been suggested by Dongju Zhang, we proposed the palladium-silver dinuclear species as reactive intermediates in this work. The substituent effect was estimated to unravel the e-CMD nature of the rate-determining C-H activation step. Based on this realization, the exptl. observed substrate scope and ligand choice have also been rationalized.

Organic & Biomolecular Chemistry published new progress about Arylation catalysts. 23088-24-6 belongs to class quinoxaline, and the molecular formula is C9H5N3, Category: quinoxaline.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Minisci, Francesco; Recupero, Francesco; Punta, Carlo; Gambarotti, Cristian; Antonietti, Fabrizio; Fontana, Francesca; Pedulli, Gian Franco published the artcile< A novel, selective free-radical carbamoylation of heteroaromatic bases by Ce(IV) oxidation of formamide, catalyzed by N-hydroxyphthalimide>, Related Products of 5182-90-1, the main research area is carbamoylation heteroaromatic compound cerium oxidation formamide hydroxyphthalimide catalyst.

The Ce(IV)-NHPI system was used to generate a carbamoyl radical by oxidation of formamide; this nucleophilic radical has been successfully used in the carbamoylation of heteroaromatic bases.

Chemical Communications (Cambridge, United Kingdom) published new progress about Carbamoylation. 5182-90-1 belongs to class quinoxaline, and the molecular formula is C9H7N3O, Related Products of 5182-90-1.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Makaravage, Katarina J.; Shao, Xia; Brooks, Allen F.; Yang, Lingyun; Sanford, Melanie S.; Scott, Peter J. H. published the artcile< Copper(II)-Mediated [11C]Cyanation of Arylboronic Acids and Arylstannanes>, Formula: C9H5N3, the main research area is arylboronic acid cyanation copper; arylnitrile preparation; copper radiocyanation cyanation catalyst.

A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-[11C]-nitriles is reported. This method is operationally simple, uses com. available reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity [11C]perampanel in 10% nondecay-corrected radiochem. yield (RCY).

Organic Letters published new progress about Arylboronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 23088-24-6 belongs to class quinoxaline, and the molecular formula is C9H5N3, Formula: C9H5N3.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Heilporn, Sylvie; Kaisin, Michel; Flammang, Robert published the artcile< Study of the mass spectral fragmentation processes in dinitroquinoxalines using tandem methodologies>, Product Details of C8H4ClN3O2, the main research area is dinitro quinoxaline mass spectra fragmentation mechanism.

The fragmentations of 11 isomeric dinitroquinoxalines following electron ionization were studied, making use of tandem mass-spectrometry methodologies such as collisional activation (CA), various linked-scanning (LS) experiments, and mass-analyzed ion-kinetic-energy (MIKE) spectrometry. For 5,6- (I) and 6,7-dinitroquinoxaline (II), the most abundant fragment ion at m/z 116 is generated for II by successive losses of NO2·, CO, and NO·, whereas for I it is the result of 2 main competing fragmentation routes. 5,7-Dinitroquinoxaline fragmentation differs significantly, as an abundant and quite characteristic ion at m/z 127 results from consecutive eliminations of NO2· and HNO2. Addnl. substitution of the pyrazine or the benzene ring strongly modifies the reactivity.

European Mass Spectrometry published new progress about Fragmentation reaction. 6272-25-9 belongs to class quinoxaline, and the molecular formula is C8H4ClN3O2, Product Details of C8H4ClN3O2.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Caronna, T.; Gambarotti, C.; Palmisano, L.; Punta, C.; Recupero, F. published the artcile< Sunlight induced functionalization of some heterocyclic bases in the presence of polycrystalline TiO2>, Recommanded Product: Quinoxaline-2-carboxamide, the main research area is quinoline sunlight functionalization titanium oxide; photochem oxidation sunlight functionalization titanium oxide; quinoxaline sunlight functionalization titanium oxide; quinaldine methylquinoline sunlight functionalization titanium oxide; lepidine methylquinoline sunlight functionalization titanium oxide.

The functionalization of various heterocyclic bases induced by sunlight is reported. The photoreaction occurred with higher yield in a liquid-solid heterogeneous system in the presence of polycrystalline TiO2 (anatase) than in a homogeneous system under the same exptl. conditions.

Chemical Communications (Cambridge, United Kingdom) published new progress about Amidation. 5182-90-1 belongs to class quinoxaline, and the molecular formula is C9H7N3O, Recommanded Product: Quinoxaline-2-carboxamide.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Aoki, Katsuyuki; Obata, Tatsuhiro; Yamazaki, Yosuke; Mori, Yoshikazu; Hirokawa, Hiroko; Koseki, Jun-ichi; Hattori, Tomohisa; Niitsu, Kazuaki; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi published the artcile< Potent platelet-derived growth factor-β receptor (PDGF-βR) inhibitors: synthesis and structure-activity relationships of 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}quinoxalin-2(1H)-one derivatives>, Category: quinoxaline, the main research area is pyrrolopyridinylquinoxalinone preparation platelet derived growth factor receptor inhibitor.

The authors found previously that 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}quinoxalin-2(1H)-one has considerable potency as a PDGF inhibitor. This compound showed potent inhibitory activity in a PDGF-induced CPA (Cell Proliferation Assay) and APA (Auto-Phosphorylation Assay) (IC50 = 0.05 μmol/l in CPA, 0.03 μmol/l in APA). Therefore, the authors tried to develop a novel and effective PDGF-βR inhibitor by optimizing a series of its derivatives The authors found that trifluoroacetic acid (TFA)-catalyzed coupling of pyrrolo[2,3-b]pyridines with quinoxalin-2-ones proceeded efficiently under mild oxidation condition with manganese(IV) oxide (MnO2) in situ, so this method was applied to prepare a series of derivatives Results of in vitro screening of newly synthesized derivatives identified compound I (R = pentyl) as having potent (IC50 = 0.014 μmol/l in CPA, 0.007 μmol/l in APA) and selective [IC50 values against vascular endothelial growth factor receptor 2 (VEGFR2, kinase domain region, KDR), epidermal growth factor receptor (EGFR), c-Met (hepatocyte growth factor receptor) and insulin growth factor I receptor (IGF-IR)/IC50 against PDGFR were each >1000] inhibitory activity. Moreover, in this series of derivatives, 7-[3-(cyclohexylmethyl)thioureido]-3-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinoxalin-2(1H)-one showed potent inhibitory activity toward both PDGF- and VEGF-induced signaling (PDGFR: IC50 = 0.004 μmol/l in CPA, 0.0008 μmol/l in APA, KDR: IC50 = 0.008 μmol/l in APA). Herein, the authors report a new and convenient synthetic method for this series of derivatives and its SAR study.

Chemical & Pharmaceutical Bulletin published new progress about Platelet-derived growth factor receptor β Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Category: quinoxaline.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Li, Yi-Na; Li, Xue-Lin; Wu, Jin-Bo; Jiang, Hong; Liu, Yunmei; Guo, Yu; Zeng, Yao-Fu; Wang, Zhen published the artcile< Metal-free regioselective nitration of quinoxalin-2(1H)-ones with tert-butyl nitrite>, Reference of 89898-96-4, the main research area is nitro quinoxalinone preparation regioselective; quinoxalinone tert butyl nitrite metal free nitration.

A metal-free coupling of quinoxalin-2(1H)-ones with tert-Bu nitrite has been developed. Distinctly from the previous functionalization of quinoxalin-2(1H)-ones, this nitration reaction took place selectively at the C7 or C5 position of the Ph ring, affording a series of 7-nitro and 5-nitro quinoxalin-2(1H)-ones in moderate to good yields. Preliminary mechanistic studies revealed that the reaction may involve a radical process.

Organic & Biomolecular Chemistry published new progress about Coupling reaction, regioselective. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Reference of 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Deng, Jing; Feng, Enguang; Ma, Sheng; Zhang, Yan; Liu, Xiaofeng; Li, Honglin; Huang, Huang; Zhu, Jin; Zhu, Weiliang; Shen, Xu; Miao, Liyan; Liu, Hong; Jiang, Hualiang; Li, Jian published the artcile< Design and synthesis of small molecule RhoA inhibitors: a new promising therapy for cardiovascular diseases?>, Related Products of 89898-96-4, the main research area is quinoxaline derivative preparation SAR drug screen RhoA inhibitory; cardiovascular disease.

RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromols., and to our knowledge, small mol.-based inhibitors have not been reported. In this study, a series of first-in-class small mol. RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chem. synthesis and bioassay. Virtual screening of ∼200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level. Compound I was selected for further structure modifications in considering binding activity and synthesis ease. Forty-one new compounds were designed and synthesized accordingly. It was found that eight showed high RhoA inhibition activities with IC50 values of 1.24 to 3.00 μM. A pharmacol. assay indicated that two compounds II and III demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.

Journal of Medicinal Chemistry published new progress about Amination. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Related Products of 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider