Author: Jessica.F

伪₂ Adrenoceptor Agonists as Potential Analgesic Agents. 3. Imidazolylmethylthiophenes was written by Boyd, Robert E.;Rasmussen, C. Royce;Press, Jeffery B.;Raffa, Robert B.;Codd, Ellen E.;Connelly, Charlene D.;Li, Quan S.;Martinez, Rebecca P.;Lewis, Martin A.;Almond, Harold R.;Reitz, Allen B.. And the article was included in Journal of Medicinal Chemistry in 2001.COA of Formula: C5H2Cl2O2S This article mentions the following:

A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the 伪₂ adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the 伪_2D adrenoceptor, the 4-bromo analogs I [R = H, Me] were very active in the rat abdominal irritant test (RAIT) with ED₅₀ doses of 0.38 and 0.31 mg/kg, resp. A pharmacophore model based on the biol. activity of the present series, dexmedetomidine and its conformationally restrained analogs was constructed. In the experiment, the researchers used many compounds, for example, 2,5-Dichlorothiophene-3-carboxylic acid (cas: 36157-41-2COA of Formula: C5H2Cl2O2S).

2,5-Dichlorothiophene-3-carboxylic acid (cas: 36157-41-2) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.COA of Formula: C5H2Cl2O2S

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Study on d⁰ Metal-Catalyzed Alkyl-Alkyl Cross-Coupling Enabled by a Redox-Active Ligand was written by Belli, Roman G.;Tafuri, Victoria C.;Joannou, Matthew V.;Roberts, Courtney C.. And the article was included in ACS Catalysis in 2022.SDS of cas: 76-83-5 This article mentions the following:

Herein, a redox-active ligand-enabled alkyl-alkyl cross-coupling using a d⁰ metal was described. This tris(amido) ScIII complex as well as the oxidized variant was thoroughly characterized (NMR, X-ray, EPR, CV, UV-vis, DFT). Insight into the likely radical nature of the mechanism is disclosed. Addnl., a substrate scope that includes functional groups incompatible with late-transition-metal catalysis and both coupling partners bearing 尾-hydrogens was reported. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5SDS of cas: 76-83-5).

(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.SDS of cas: 76-83-5

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Mechanism-Based QSAR Modeling of Skin Sensitization was written by Dearden, J. C.;Hewitt, M.;Roberts, D. W.;Enoch, S. J.;Rowe, P. H.;Przybylak, K. R.;Vaughan-Williams, G. D.;Smith, M. L.;Pillai, G. G.;Katritzky, A. R.. And the article was included in Chemical Research in Toxicology in 2015.Recommanded Product: 1-Chlorooctadecane This article mentions the following:

Many chems. can induce skin sensitization, and there is a pressing need for non-animal methods to give a quant. indication of potency. Using two large published data sets of skin sensitizers, we have allocated each sensitizing chem. to one of 10 mechanistic categories and then developed good QSAR models for the seven categories that have a sufficient number of chems. to allow modeling. Both internal and external validation checks showed that each model had good predictivity. In the experiment, the researchers used many compounds, for example, 1-Chlorooctadecane (cas: 3386-33-2Recommanded Product: 1-Chlorooctadecane).

1-Chlorooctadecane (cas: 3386-33-2) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Recommanded Product: 1-Chlorooctadecane

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Judging Enzyme-Responsive Micelles by Their Covers: Direct Comparison of Dendritic Amphiphiles with Different Hydrophilic Blocks was written by Slor, Gadi;Olea, Alis R.;Pujals, Silvia;Tigrine, Ali;De La Rosa, Victor R.;Hoogenboom, Richard;Albertazzi, Lorenzo;Amir, Roey J.. And the article was included in Biomacromolecules in 2021.Formula: C19H15Cl This article mentions the following:

Enzymically degradable polymeric micelles have great potential as drug delivery systems, allowing the selective release of their active cargo at the site of disease. Furthermore, enzymic degradation of the polymeric nanocarriers facilitates clearance of the delivery system after it has completed its task. While extensive research is dedicated toward the design and study of the enzymically degradable hydrophobic block, there is limited understanding on how the hydrophilic shell of the micelle can affect the properties of such enzymically degradable micelles. In this work, we report a systematic head-to-head comparison of well-defined polymeric micelles with different polymeric shells and two types of enzymically degradable hydrophobic cores. To carry out this direct comparison, we developed a highly modular approach for preparing clickable, spectrally active enzyme-responsive dendrons with adjustable degree of hydrophobicity. The dendrons were linked with three different widely used hydrophilic polymers-poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid) using the CuAAC click reaction. The high modularity and mol. precision of the synthetic methodol. enabled us to easily prepare well-defined amphiphiles that differ either in their hydrophilic block composition or in their hydrophobic dendron. The micelles of the different amphiphiles were thoroughly characterized and their sizes, critical micelle concentrations, drug loading, stability, and cell internalization were compared. We found that the micelle diameter was almost solely dependent on the hydrophobicity of the dendritic hydrophobic block, whereas the enzymic degradation rate was strongly dependent on the composition of both blocks. Drug encapsulation capacity was very sensitive to the type of the hydrophilic block, indicating that, in addition to the hydrophobic core, the micellar shell also has a significant role in drug encapsulation. Incubation of the spectrally active micelles in the presence of cells showed that the hydrophilic shell significantly affects the micellar stability, localization, cell internalization kinetics, and the cargo release mechanism. Overall, the high mol. precision and the ability of these amphiphiles to report their disassembly, even in complex biol. media, allowed us to directly compare the different types of micelles, providing striking insights into how the composition of the micelle shells and cores can affect their properties and potential to serve as nanocarriers. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5Formula: C19H15Cl).

(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Organic chlorides can cause corrosion in pipelines, valves and condensers, and cause catalyst poisoning. The hydrocarbon processing industry (HPI) and others are affected by damage caused by these substances. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Formula: C19H15Cl

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Novel Biphenyl Pyridines as Potent Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction was written by Wang, Tianyu;Cai, Shi;Wang, Mingming;Zhang, Wanheng;Zhang, Kuojun;Chen, Dong;Li, Zheng;Jiang, Sheng. And the article was included in Journal of Medicinal Chemistry in 2021.Reference of 65515-32-4 This article mentions the following:

The design, synthesis and in-vitro and in-vivo evaluation of a series of novel biphenyl pyridines, I [R = Ph, 3-methoxyphenyl, 1,3-benzodioxol-5-yl, etc.; R¹ = H, (2-hydroxyethylamino)methyl; R² = methoxycarbonyl, (2-hydroxyethylamino)methyl, [[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl, etc.; R³ = H, MeO] as the inhibitors of PD-1/PD-L1 was reported. Compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] was found to inhibit the PD-1/PD-L1 interaction with an IC₅₀ value of 3.8 卤 0.3 nM and enhance the killing activity of tumor cells by immune cells. Compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] displayed great pharmacokinetics (oral bioavailability of 22%) and significant in-vivo antitumor activity in a CT26 mouse model. Flow cytometry and immunohistochem. data indicated that compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] activates the immune activity in tumors. These results suggest that compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] is a promising small-mol. inhibitor against the PD-1/PD-L1 axis and merits further development. In the experiment, the researchers used many compounds, for example, Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4Reference of 65515-32-4).

Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Reference of 65515-32-4

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Metathesis-active ligands enable a catalytic functional group metathesis between aroyl chlorides and aryl iodides was written by Lee, Yong Ho;Morandi, Bill. And the article was included in Nature Chemistry in 2018.Synthetic Route of C8H4ClNO This article mentions the following:

Current methods for functional group interconversion have, for the most part, relied on relatively strong driving forces which often require highly reactive reagents to generate irreversibly a desired product in high yield and selectivity. These approaches generally prevent the use of the same catalytic strategy to perform the reverse reaction. Here we describe a catalytic functional group metathesis approach to interconvert, under CO-free conditions, two synthetically important classes of electrophiles that are often employed in the preparation of pharmaceuticals and agrochems.-aroyl chlorides (ArCOCl) and aryl iodides (ArI). Our reaction design relies on the implementation of a key reversible ligand C-P bond cleavage event, which enables a non-innocent, metathesis-active phosphine ligand to mediate a rapid aryl group transfer between the two different electrophiles. Beyond enabling a practical and safer approach to the interconversion of ArCOCl and ArI, this type of ligand non-innocence provides a blueprint for the development of a broad range of functional group metathesis reactions employing synthetically relevant aryl electrophiles. In the experiment, the researchers used many compounds, for example, 3-Cyanobenzoyl chloride (cas: 1711-11-1Synthetic Route of C8H4ClNO).

3-Cyanobenzoyl chloride (cas: 1711-11-1) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Synthetic Route of C8H4ClNO

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Design and Synthesis of a Screening Library Using the Natural Product Scaffold 3-Chloro-4-hydroxyphenylacetic Acid was written by Kumar, Rohitesh;Sadowski, Martin C.;Levrier, Claire;Nelson, Colleen C.;Jones, Amy J.;Holleran, John P.;Avery, Vicky M.;Healy, Peter C.;Davis, Rohan A.. And the article was included in Journal of Natural Products in 2015.Quality Control of Methyl 3-chloro-4-hydroxyphenylacetate This article mentions the following:

The fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (I) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. A 20-membered amide library, II (R = CH₂CH₂CHMe₂, morpholinoethyl, CH₂CH₂NMe₂, etc.), III (R¹, R² = H, F, R³ = H, Br, Cl, F), and IV, was generated by first converting I to Me (3-chloro-4-hydroxyphenyl)acetate, then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. The structures of the synthetic analogs II, III, and IV were elucidated by spectroscopic data anal. The structures of compounds III (R¹ = F, R² = R³ = H), IV (R¹ = R² = H, R³ = F), and the hydrate of II (R = CH₂CH₂NMe₂) were confirmed by single X-ray crystallog. anal. All compounds were evaluated for cytotoxicity against a human prostate cancer cell line (LNCaP) and for antiparasitic activity toward Trypanosoma brucei brucei and Plasmodium falciparum and showed no significant activity at 10 渭M. The library was also tested for effects on the lipid content of LNCaP and PC-3 prostate cancer cells, and it was demonstrated that the fluorobenzyl analogs IV (R¹ = R² = H, R³ = F; R¹ = R³ = H, R² = F; R¹ = F, R² = R³ = H) significantly reduced cellular phospholipid and neutral lipid levels. In the experiment, the researchers used many compounds, for example, Methyl 3-chloro-4-hydroxyphenylacetate (cas: 57017-95-5Quality Control of Methyl 3-chloro-4-hydroxyphenylacetate).

Methyl 3-chloro-4-hydroxyphenylacetate (cas: 57017-95-5) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Quality Control of Methyl 3-chloro-4-hydroxyphenylacetate

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Ethyl 3-nitro-4-(n-propylamino)benzoate was written by Zhang, Guo-Hua;Wu, Yong Zhong;Li, Hao-Yuan;Liu, Bo-Nian;Guo, Cheng. And the article was included in Acta Crystallographica, Section E: Structure Reports Online in 2009.Computed Properties of C9H8ClNO4 This article mentions the following:

In the mol. of the title compound, C₁₂H₁₆N₂O₄, an intramol. N-H…O hydrogen bond results in the formation of a six-membered ring having an envelope conformation. In the crystal structure, a bifurcated intra/intermol. N-H…(O,O) hydrogen bond generates inversion dimers. Crystallog. data are given. In the experiment, the researchers used many compounds, for example, Ethyl 4-chloro-3-nitrobenzoate (cas: 16588-16-2Computed Properties of C9H8ClNO4).

Ethyl 4-chloro-3-nitrobenzoate (cas: 16588-16-2) belongs to organic chlorides. Organic chlorides can cause corrosion in pipelines, valves and condensers, and cause catalyst poisoning. The hydrocarbon processing industry (HPI) and others are affected by damage caused by these substances. Alkanes and aryl alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control.Computed Properties of C9H8ClNO4

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer was written by Langston, Steven P.;Grossman, Stephen;England, Dylan;Afroze, Roushan;Bence, Neil;Bowman, Douglas;Bump, Nancy;Chau, Ryan;Chuang, Bei-Ching;Claiborne, Christopher;Cohen, Larry;Connolly, Kelly;Duffey, Matthew;Durvasula, Nitya;Freeze, Scott;Gallery, Melissa;Galvin, Katherine;Gaulin, Jeffrey;Gershman, Rachel;Greenspan, Paul;Grieves, Jessica;Guo, Jianping;Gulavita, Nanda;Hailu, Shumet;He, Xingyue;Hoar, Kara;Hu, Yongbo;Hu, Zhigen;Ito, Mitsuhiro;Kim, Mi-Sook;Lane, Scott Weston;Lok, David;Lublinsky, Anya;Mallender, William;McIntyre, Charles;Minissale, James;Mizutani, Hirotake;Mizutani, Miho;Molchinova, Nina;Ono, Koji;Patil, Ashok;Qian, Mark;Riceberg, Jessica;Shindi, Vaishali;Sintchak, Michael D.;Song, Keli;Soucy, Teresa;Wang, Yana;Xu, He;Yang, Xiaofeng;Zawadzka, Agatha;Zhang, Ji;Pulukuri, Sai M.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C8H9Cl This article mentions the following:

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclin. tumor models, culminating in the identification of the clin. mol. TAK-981. In the experiment, the researchers used many compounds, for example, 1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9Computed Properties of C8H9Cl).

1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Computed Properties of C8H9Cl

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases was written by Wang, Pei-Yi;Wang, Ming-Wei;Zeng, Dan;Xiang, Meng;Rao, Jia-Rui;Liu, Qing-Qing;Liu, Li-Wei;Wu, Zhi-Bing;Li, Zhong;Song, Bao-An;Yang, Song. And the article was included in Journal of Agricultural and Food Chemistry in 2019.Application of 620-19-9 This article mentions the following:

The emergence and widespread occurrence of plant bacterial diseases that cause global production constraints have become major challenges to agriculture worldwide. To promote the discovery and development of new bactericides, imidazole-labeled 1,3,4-oxadiazole thioethers were first fabricated by integrating the crucially bioactive scaffolds of the imidazole motif and 1,3,4-oxadiazole skeleton in a single mol. architecture. Subsequently, a superior antibacterial compound A₆ was gradually discovered possessing excellent competence against plant pathogens Xanthomonas oryzae pv oryzae and Xanthomonas axonopodis pv citri with EC₅₀ values of 0.734 and 1.79 渭g/mL, resp. These values were better than those of com. agents bismerthiazol (92.6 渭g/mL) and thiodiazole copper (77.0 渭g/mL). Further modifying the imidazole moiety into the imidazolium scaffold led to the discovery of an array of potent antibacterial compounds providing the corresponding min. EC₅₀ values of 0.295 and 0.607 渭g/mL against the two strains. Moreover, a plausible action mechanism for attacking pathogens was proposed based on the concentration dependence of SEM, transmission electron microscopy, and fluorescence microscopy images. Given the simple mol. structures, easy synthetic procedure, and highly efficient bioactivity, imidazole (or imidazolium)-labeled 1,3,4-oxadiazole thioethers can be further explored and developed as promising indicators for the development of com. drugs. In the experiment, the researchers used many compounds, for example, 1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9Application of 620-19-9).

1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Application of 620-19-9

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics