Month: October 2022

《A New Class of Dengue and West Nile Virus Protease Inhibitors with Submicromolar Activity in Reporter Gene DENV-2 Protease and Viral Replication Assays》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Kuehl, Nikos; Graf, Dominik; Bock, Josephine; Behnam, Mira A. M.; Leuthold, Mila-Mareen; Klein, Christian D.. Name: 4-Cyanobenzyl bromide The article mentions the following:

Dengue and West Nile virus are rapidly spreading global pathogens for which no specific therapeutic treatments are available. One of the promising targets for drug discovery against dengue and other flaviviruses is the viral serine protease NS2B-NS3. We present the design, synthesis, and in vitro and cellular characterization of a novel chemotype of potent small-mol. non-peptidic dengue protease inhibitors derived from 4-benzyloxyphenylglycine. A newly developed luciferase-based DENV-2 protease reporter system in HeLa cells (DENV2proHeLa) was employed to determine the activity of the compounds in a cellular environment. Specificity and selectivity of the DENV2proHeLa system were confirmed by viral titer reduction assays. The compounds reach low micromolar to upper nanomolar inhibitory potency in cell-based assays, are selective against other serine proteases, and do not show relevant cytotoxicity. An extensive structure-activity relationship study provides a perspective for further drug development against flaviviral infections. In the experiment, the researchers used many compounds, for example, 4-Cyanobenzyl bromide(cas: 17201-43-3Name: 4-Cyanobenzyl bromide)

4-Cyanobenzyl bromide(cas: 17201-43-3) is a white solid. Its melting point is 113-117°C, and flash point is 125.1°C. It is insoluble in water at 20°C. It is stable under normal temperatures and pressures. It should be stored at 0-5°C.Name: 4-Cyanobenzyl bromide

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《Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator》 was written by Rustler, Karin; Maleeva, Galyna; Gomila, Alexandre M. J.; Gorostiza, Pau; Bregestovski, Piotr; Koenig, Burkhard. Recommanded Product: 3-Oxo-3-phenylpropanenitrile And the article was included in Chemistry – A European Journal in 2020. The article conveys some information:

Optogenetic and photopharmacol. tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biol. evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABAARs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition. The experimental process involved the reaction of 3-Oxo-3-phenylpropanenitrile(cas: 614-16-4Recommanded Product: 3-Oxo-3-phenylpropanenitrile)

3-Oxo-3-phenylpropanenitrile(cas: 614-16-4) has been used in the synthesis of substituted naphtho[1,8-bc]pyrans. It was also used as building block in the preparation of 4H-pyrans, 2-pyridones, furans and carbocyclics.Recommanded Product: 3-Oxo-3-phenylpropanenitrile

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《Regioselective functionalization of aryl azoles as powerful tool for the synthesis of pharmaceutically relevant targets》 was written by Lutter, Ferdinand H.; Grokenberger, Lucie; Perego, Luca Alessandro; Broggini, Diego; Lemaire, Sebastien; Wagschal, Simon; Knochel, Paul. COA of Formula: C7H3BrFN And the article was included in Nature Communications in 2020. The article conveys some information:

The metalation of 1-aryl-1H-1,2,3-triazoles and other related heterocycles with sterically hindered metal-amide bases were investigated. A room temperature and highly regioselective ortho-magnesiation of several aryl azoles using a tailored magnesium amide, TMPMgBu (TMP = 2,2,6,6-tetramethylpiperidyl) in hydrocarbon solvents followed by an efficient Pd-catalyzed arylation was reported. This scalable and selective reaction allows variation of the initial substitution pattern of the aryl ring, the nature of the azole moiety, as well as the nature of the electrophile. This versatile method can be applied to the synthesis of bioactive azole derivatives and complements existing metal-mediated ortho-functionalizations. In the experiment, the researchers used 4-Bromo-2-fluorobenzonitrile(cas: 105942-08-3COA of Formula: C7H3BrFN)

4-Bromo-2-fluorobenzonitrile(cas:105942-08-3) is used as a OLED intermediate, Pharmaceutical, electronic and chemical intermediate.COA of Formula: C7H3BrFN It is used in the synthesis of heterocycles and liquid crystals.

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Wei, Yueting; Liu, Ping; Liu, Yali; He, Jing; Li, Xuezhen; Li, Shiwu; Zhao, Jixing published their research in Organic & Biomolecular Chemistry in 2021. The article was titled 《NIS-promoted three-component reaction of 3-oxo-3-arylpropanenitriles with arylsulfonyl hydrazides》.Related Products of 614-16-4 The article contains the following contents:

A new three-component reaction of 3-oxo-3-arylpropanenitriles with arylsulfonyl hydrazides was established and an expanded inventory of 3-aryl-4-(arylthio)-1H-pyrazol-5-amines were synthesized by sequential cyclization and sulfenylation reactions under the action of NIS. In addition to the attractive features of multicomponent reactions, the protocol presented broad substrate scope, good functional group tolerance and mild reaction conditions. The utility of this procedure was further established by gram-scale synthesis as well as the diversified transformations of the products to useful compounds After reading the article, we found that the author used 3-Oxo-3-phenylpropanenitrile(cas: 614-16-4Related Products of 614-16-4)

3-Oxo-3-phenylpropanenitrile(cas: 614-16-4) has been used to produce 2-benzoyl-3-furan-2-yl-acrylonitrile. It is an active methylene compound, useful in heterocyclic synthesis, e.g. polyfunctional pyridines and pyrimidines.Related Products of 614-16-4

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Lu, Wen-Xiu; Xing, Jian; Sun, Yijia; Huang, Qinge; Deng, Zhenwei; Mao, Jian-Gang published their research in Organic & Biomolecular Chemistry in 2021. The article was titled 《Palladium-catalyzed and alcohol-enabled transformation to synthesize benzocyclic ketones》.Formula: C7H4BrN The article contains the following contents:

A highly effective palladium-catalyzed and alc.-promoted transformation of nitriles to synthesize benzocyclic ketones was described. It provided a straightforward access to potentially valuable indanone compounds in high yields in the presence of alc. It avoided the usage of carbon monoxide or an addnl. hydrolysis procedure. In the part of experimental materials, we found many familiar compounds, such as 2-Bromobenzonitrile(cas: 2042-37-7Formula: C7H4BrN)

2-Bromobenzonitrile(cas: 2042-37-7) is a precursor to the quinazolinones, a class of drugs used to treat autoimmune diseases and coronary heart disease. This substrate molecule undergoes a palladium-catalyzed coupling reaction to form an aromatic ring. The light emission from this reaction can be seen in the reaction solution.Formula: C7H4BrN

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Joy, F.; Peter, F.; Gokul, P. C.; Nizam, A.; Chinnam, S. published an article in 2022. The article was titled 《UV-Promoted Metal- and Photocatalyst-Free Direct Conversion of Aromatic Aldehydes to Nitriles》, and you may find the article in Russian Journal of Organic Chemistry.Quality Control of 4-Fluorobenzonitrile The information in the text is summarized as follows:

An efficient, simple and catalyst-free UV-induced functional group transformation of aromatic aldehydes to nitriles was reported. The developed strategy delivered various functionalized aromatic nitriles with high yields and purity. The UV irradiation activated the carbonyl group of aldehydes and lead to the formation of aldoxime intermediate, further resulting in the generation of nitriles. The striking highlights of the reported methodol. were simple reaction conditions, good yields, UV-promoted transformation and catalyst-free synthesis. Due to the above-mentioned advantages, the methodol. provided a hand towards environmentally friendly chem. synthesis. In the experiment, the researchers used many compounds, for example, 4-Fluorobenzonitrile(cas: 1194-02-1Quality Control of 4-Fluorobenzonitrile)

4-Fluorobenzonitrile(cas: 1194-02-1) is used in the synthesis of flurenones, pharmaceutical prerequisites, as well as opiod receptor antagonists.Quality Control of 4-Fluorobenzonitrile

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In 2022,Nguyen, Thuy; Gamage, Thomas F.; Finlay, David B.; Decker, Ann M.; Langston, Tiffany L.; Barrus, Daniel; Glass, Michelle; Li, Jun-Xu; Kenakin, Terry P.; Zhang, Yanan published an article in Journal of Medicinal Chemistry. The title of the article was 《Development of 3-(4-Chlorophenyl)-1-(phenethyl)urea Analogues as Allosteric Modulators of the Cannabinoid Type-1 Receptor: RTICBM-189 is Brain Penetrant and Attenuates Reinstatement of Cocaine-Seeking Behavior》.Formula: C8H6BrN The author mentioned the following in the article:

We have shown that CB1 receptor neg. allosteric modulators (NAMs) attenuated the reinstatement of cocaine-seeking behaviors in rats. In an effort to further define the structure-activity relationships and assess the druglike properties of the 3-(4-chlorophenyl)-1-(phenethyl)urea-based CB1 NAMs that we recently reported, we introduced substituents of different electronic properties and sizes to the phenethyl group and evaluated their potency in CB1 calcium mobilization, cAMP, and GTPγS assays. We found that 3-position substitutions such as Cl, F, and Me afforded enhanced CB1 potency, whereas 4-position analogs were generally less potent. The 3-chloro analog (31, RTICBM-189)(I) showed no activity at >50 protein targets and excellent brain permeation but relatively low metabolic stability in rat liver microsomes. Pharmacokinetic studies in rats confirmed the excellent brain exposure of 31 with a brain/plasma ratio Kp of 2.0. Importantly, i.p. administration of 31 significantly and selectively attenuated the reinstatement of the cocaine-seeking behavior in rats without affecting locomotion. In addition to this study using 2-(3-Bromophenyl)acetonitrile, there are many other studies that have used 2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5Formula: C8H6BrN) was used in this study.

2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5) has been used in the synthesis of 2-(1-cyano-1-(3-bromophenyl))methylidene-3-phenylthiazolidine-4,5-dione or a series of aminoethylbiphenyls, novel 5-HT7 receptor ligands.Formula: C8H6BrN

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Application of 105942-08-3In 2018 ,《Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Liu, Jian; Qian, Chengbo; Zhu, Yehua; Cai, Jianguo; He, Yufang; Li, Jie; Wang, Tianlin; Zhu, Haohao; Li, Zhi; Li, Wei; Hu, Lihong. The article conveys some information:

Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven’t been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and mol. hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9 μM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition. In addition to this study using 4-Bromo-2-fluorobenzonitrile, there are many other studies that have used 4-Bromo-2-fluorobenzonitrile(cas: 105942-08-3Application of 105942-08-3) was used in this study.

4-Bromo-2-fluorobenzonitrile(cas:105942-08-3) is used as a OLED intermediate, Pharmaceutical, electronic and chemical intermediate.Application of 105942-08-3 It is used in the synthesis of heterocycles and liquid crystals.

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Safety of 4-Cyano-3-fluorophenyl 4-butylbenzoateOn June 3, 2015, Rozwadowski, Tomasz; Massalska-Arodz, Maria; Kolek, Lukasz; Grzybowska, Katarzyna; Bak, Andrzej; Chledowska, Krystyna published an article in Crystal Growth & Design. The article was 《Kinetics of Cold Crystallization of 4-Cyano-3-fluorophenyl 4-Butylbenzoate (4CFPB) Glass Forming Liquid Crystal. I. Nonisothermal Process As Studied by Microscopic, Calorimetric, and Dielectric Methods》. The article mentions the following:

For 4-cyano-3-fluorophenyl 4-butylbenzoate (4CFPB), the process of the crystallization of the CrII phase was studied in microscopic (POM), calorimetric (DSC), and dielec. (BDS) nonisothermal experiments with various (0.5-50 K/min) heating of the metastable nematic phase obtained from its glass. Growth of areas of crystal CrII in the microscopic texture of nematic phase during heating allows estimation of degree of crystallinity D(T) vs temperature curves similar to these obtained basing on DSC heat flow curves and for slow heating with help of dielec. relaxation (BDS) method. Two types of CrII crystallization mechanisms seem to be identified: (1) strong ϕ dependence on temperature of full crystallization Tc(ϕ) and half time of crystallization t1/2(ϕ) on slow heating up to 5 K/min points to diffusion-controlled mechanism with the energy barrier 57 kJ/mol, and (2) small effect of faster heating on Tc(ϕ) and t1/2(ϕ) seems to illustrate thermodn. mechanism with energy barrier 180 kJ/mol. The scenario of two mechanisms of CrII crystallization is in agreement with the results of new method proposed by Mo et al., using combination of Avrami and Ozawa equations for description of nonisothermal crystallization In addition to crystallization of CrII of 4CFPB, at higher temperature range CrII-CrI transformation to a stable CrI crystal was digitalized based on microscopic and DCS results for heating at 1 K/min. In the part of experimental materials, we found many familiar compounds, such as 4-Cyano-3-fluorophenyl 4-butylbenzoate(cas: 86776-52-5Safety of 4-Cyano-3-fluorophenyl 4-butylbenzoate)

4-Cyano-3-fluorophenyl 4-butylbenzoate(cas: 86776-52-5) is a member of aromaticfluorinated building blocks. Depending on which substituents are present, fluoroaromatic intermediates can be converted into fluorinated or fluorine-free commercial end products.Fluorine-containing aromatics have been incorporated into drugs (hypnotics, tranquilizers, antiinflammatory agents, analgesics, antibacterials).Safety of 4-Cyano-3-fluorophenyl 4-butylbenzoate

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In 1954,Journal of the Chemical Society included an article by Gray, G. W.; Jones, Brynmor. Safety of 5-Amino-1-naphthonitrile. The article was titled 《The preparation of 4- and 5-n-alkoxy-1-naphthoic and 6-and 7-n-alkoxy-2-naphthoic acids》. The information in the text is summarized as follows:

1-Naphthol was alkylated with NaOEt and the n-alkyl bromide or iodide by boiling 8 h. in EtOH. Distillation under reduced pressure gives the following ethers in 65-70% yield (b. p./mm. given): Me 134°/13, Et 152°/17 (m. 5°), Pr 143°/3, Bu 160°/4 (m. 19.5°), pentyl 173°/6 (m. 29.5°), hexyl 166°/4 (m. -3°), heptyl 171°/5, octyl 189°/5, nonyl 185°/4, decyl 212°/4, dodecyl 227°/3, hexadecyl 258°/1 (m. 31°), octadecyl 236°/10-2 (m. 50.5°). The 1-n-alkoxynaphthalenes were brominated with IBr in CHCl3 at 10-20°. The CHCl3 is removed and the 4-Br ethers are distilled under reduced pressure, being obtained in 65-75% yields (b. p./mm. given): Me 159°/4, Et 158°/3 (m. 48.5°), Pr 188°/8 (m. 31°), Bu 199°/5 (m. 25°), pentyl 181°/3 (m. 47.5°), hexyl 206°/5 (m. 45°). 1-n-Alkoxynaphthalenes in CS2 containing AlCl3 are treated with BrCN to form 4-n-alkoxy-1-naphthonitriles (I) in 80% yield (m. p. given): Et 88°, pentyl 60°, hexyl 62°, heptyl 54°, octyl 61°, nonyl 53°, decyl 64°, dodecyl 67°, hexadecyl 69°, octadecyl 71°. 4-n-Alkoxy-1-naphthoic acids are made from 1 g.-atom Mg turnings and 2 g. of the 1-bromonaphthalene in 25 mL. ether by refluxing 5 min. A total of 0.1 mol of the 1-bromonaphthalene in 75 mL. ether is added dropwise in 30 min. and reflux is continued 10 h. The mixture is added to ether saturated with Dry Ice. The excess CO2 is evaporated and the solution stirred with 50 mL. 17% HCl. The ether is removed and the acid washed free of MgCl2. The acids are recrystallized from glacial HOAc in 80-5% yield. Another method of forming the acids is to reflux 0.1 mol of the nitrile with 250 mL. of a solution of MeOH saturated with KOH for 15-25 h. The diluted mixture is acidified, redissolved in NaOH, and reacidified to give the following 1-carboxy analogs of I in 95-7% yields (m. p. given): Me 248°, Et 220°, Pr 203°, Bu 213.5°, pentyl 207°, hexyl 212°, heptyl 189°, octyl 183.5°, nonyl 161°, decyl 174.5°, dodecyl 147.5°, hexadecyl 136°, octadecyl 137.5°. Na 5-aminonaphthalene-1-sulfonate (70 g.) and 14 g. KCN are ground together and dry-distilled in an all-glass retort at 500-600°, the distillate is dissolved in 1.3 l. boiling 0.3N HCl, the solution is cooled and filtered, and the filtrate is neutralized with concentrated NH3 to give 22-6% 5-amino-1-naphthonitrile (II), m. 140°, b2-3 187-93°. II (0.03 mol) is dissolved in 60 mL. glacial HOAc at 80°, 60 mL. 40% H2SO4 is added with stirring, the solution is cooled to 0°, 0.06 mol NaNO2 in 30 mL. H2O is added, the solution is stirred at 0-5° until it clears, urea is used to destroy the excess NO2-, the solution is immediately added dropwise with stirring to a boiling solution of 180 mL. 40% H2SO4 in 30 min. refluxing is continued 1 h., the mixture is cooled, 300 mL. H2O is added, the solution is extracted with ether, the ether is extracted with N NaOH, and the basic extract is acidified to give 67% 5-hydroxy-1-naphthonitrile (III), m. 204-6°. After 8.4 g. III is refluxed with 50 g. KOH in 100 mL. H2O for 4-5 h., acidification gives 90% 5-hydroxy-1-naphthoic acid (IV), m. 238°; acetyl derivative, m. 204-5°. IV is methylated with Me sulfate at 40-50° in basic solution (the ester, which is a byproduct, is removed by refluxing with MeOH-KOH). The product is 5-methoxy-1-naphthoic acid (V), m. 232.5°. The following homologs of V are similarly prepared (alkyl and m. p. given): Et 201°, Pr 189°, Bu 172°, pentyl 143°, hexyl 154°, heptyl 135.5°, octyl 142.5°, nonyl 143°, decyl 137°, dodecyl 125°, hexadecyl 117.5°, octadecyl 122°. 2-Naphthol (1 mol) in 400 mL. glacial HOAc is brominated at room temperature and the resulting 1,6-dibromo-2-naphthol is reduced with mossy Sn at reflux to give 90-100% 6-bromo-2-naphthol (VI), m. 123-7°. The VI is treated with Me sulfate in alkali to give 60-70% 2-bromo-6-methoxynaphthalene (VII), m. 106-7°, b. 189-99°/20 mm. 6-Methoxy-2-naphthoic acid is formed from VII by the method of Fries and Schimmelschmidt (C.A. 20, 1616), m. 206° in 50-5% yield. AcCl treated with VII in the presence of AlCl3 in PhNO2 and distillation gives 5% 2-acetyl-6-methoxynaphthalene (VIII), m. 104-5°, b. 165-70°/3-4 mm. VIII (50 g.) in 350 mL. dioxane, is treated with NaOBr (from 140 g. NaOH, 600 mL. H2O, and 50 mL. Br) dropwise for 30 min. at 35-40° (reaching 50-5° at the end), excess Br is destroyed, 2 l. H2O is added, dioxane and CHBr3 are removed by steam distillation, and the solution is filtered and acidified with concentrated HCl to give 70-5% 6-methoxy-2-naphthoic acid (IX), m. 205-6°. IX (8 g.) is heated 2.5 h. with 35 mL. AcOH, 35 mL. 48% HBr, and 20 mL. glacial HOAc to give 6-hydroxy-2-naphthoic acid (X), m. 250° (Bz derivative, m. 257°; Ac derivative, m. 228°; phenylsulfonyl derivative, m. 228.5°). X was alkylated in 85-90% yield. The following 6-alkoxy analog of X were prepared (alkyl and m. p. given): Me 206°, Et 213°, Pr 208°, Bu 198°, pentyl 179.5°, hexyl 147°, heptyl 163°, octyl 161.5°, nonyl 147.5°, decyl 139°, dodecyl 119°, hexadecyl 107°, octadecyl 114.6°, isopentylnaphthoic acid 194.6°, 3,5,5-trimethylhexyl 170°. 7-Amino-2-naphthonitrile m. 197°. 7-Hydroxy-2-naphthonitrile, m. 186.5°. 7-Hydroxy-2-naphthoicacid m. 269-70°. 7-n-Octyloxy-2-naphthoic acid m. 142.5°, sublimes 170°/2-3 mm. 7-n-Hexadecyloxy-2-naphthoic acid m. 138°. The results came from multiple reactions, including the reaction of 5-Amino-1-naphthonitrile(cas: 72016-73-0Safety of 5-Amino-1-naphthonitrile)

5-Amino-1-naphthonitrile(cas: 72016-73-0) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Safety of 5-Amino-1-naphthonitrile

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