Month: October 2022

Lenselink, Eelke B.; Louvel, Julien; Forti, Anna F.; van Veldhoven, Jacobus P. D.; de Vries, Henk; Mulder-Krieger, Thea; McRobb, Fiona M.; Negri, Ana; Goose, Joseph; Abel, Robert; van Vlijmen, Herman W. T.; Wang, Lingle; Harder, Edward; Sherman, Woody; IJzerman, Adriaan P.; Beuming, Thijs published the artcile< Predicting Binding Affinities for GPCR Ligands Using Free-Energy Perturbation>, COA of Formula: C6H4Cl2N4, the main research area is free energy perturbation ligand preparation GPCR binding structure activity; drug discovery adenosine CXCR4 opioid receptor adrenoceptor ligand binding.

The rapid growth of structural information for G-protein-coupled receptors (GPCRs) has led to a greater understanding of their structure, function, selectivity, and ligand binding. Although novel ligands have been identified using methods such as virtual screening, computationally driven lead optimization has been possible only in isolated cases because of challenges associated with predicting binding free energies for related compounds Here, the authors provide a systematic characterization of the performance of free-energy perturbation (FEP) calculations to predict relative binding free energies of congeneric ligands binding to GPCR targets using a consistent protocol and no adjustable parameters. Using the FEP+ package, first the authors validated the protocol, which includes a full lipid bilayer and explicit solvent, by predicting the binding affinity for a total of 45 different ligands across four different GPCRs (adenosine A2AAR, β1 adrenergic, CXCR4 chemokine, and δ opioid receptors). Comparison with exptl. binding affinity measurements revealed a highly predictive ranking correlation (average spearman ρ = 0.55) and low root-mean-square error (0.80 kcal/mol). Next, the authors applied FEP+ in a prospective project, where the authors predicted the affinity of novel, potent adenosine A2A receptor (A2AR) antagonists. Four novel compounds were synthesized and tested in a radioligand displacement assay, yielding affinity values in the nanomolar range. The affinity of two out of the four novel ligands (plus three previously reported compounds) was correctly predicted (within 1 kcal/mol), including one compound with approx. a 10-fold increase in affinity compared to the starting compound Detailed analyses of the simulations underlying the predictions provided insights into the structural basis for the two cases where the affinity was overpredicted. Taken together, these results establish a protocol for systematically applying FEP+ to GPCRs and provide guidelines for identifying potent mols. in drug discovery lead optimization projects.

ACS Omega published new progress about Adenosine A2A receptors Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, COA of Formula: C6H4Cl2N4.

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

Markezich, R. L.; Zamek, O. S.; Donahue, P. E.; Williams, F. J. published the artcile< Reactions of 4-nitrophthalic anhydride with potassium fluoride and potassium nitrite>, Quality Control of 118-45-6, the main research area is nitrophthalic anhydride substitution fluoride; fluorophthalic anhydride preparation; phthalic anhydride reaction nitrite.

The reaction of potassium fluoride with 4-nitrophthalic anhydride gave good yields of 4-fluorophthalic anhydride; the reaction was run neat at 210-240° in an aprotic solvent at a lower temperature, or in refluxing acetonitrile containing a crown ether. The potassium nitrite produced in the exchange reaction was captured by unreacted 4-nitrophthalic anhydride to give the dipotassium salt of 4-nitrophthalic acid and nitrogen oxides. The reaction of potassium nitrite with several other substituted phthalic anhydrides in DMF yielded the dipotassium salts of the resp. phthalic acids.

Journal of Organic Chemistry published new progress about Substitution reaction. 118-45-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H3ClO3, Quality Control of 118-45-6.

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

Yu, Hailin; Zhu, Gang; Wang, Yinghan published the artcile< Preparation of polyimide alignment films with high photosensitivity and low solid content>, Formula: C9H7ClO, the main research area is polyimide alignment film photosensitivity liquid crystal display.

In order to reduce the cost, a polyimide (BF-CA) with high photosensitivity and low solid content was prepared by one-step method using 2,2-bis (3-amino-4-hydroxyphenyl) propane (BAP), 4,4′- (hexafluoroisopropyl) phthalic anhydride (6FDA) as monomer and cinnamoyl chloride as photosensitive group. The BF-CA films exhibit good alignment performance after non-polarised UV light (NPUVL) irradiation for 20 min. Meanwhile, the effect of solid content on the alignment performance is mainly discussed, because reducing solid content helps to reduce costs. In addition, the BF-CA shows good thermal stability. The pretilt angle of the liquid crystal cells is 0.5°, which meet the requirements of practical application in In-Plane Switching liquid crystal display.

Liquid Crystals published new progress about Anisotropy. 17082-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H7ClO, Formula: C9H7ClO.

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

Leroux, Frederic R.; Bonnafoux, Laurence; Heiss, Christophe; Colobert, Francoise; Lanfranchi, Don Antoine published the artcile< A practical transition metal-free aryl-aryl coupling method: arynes as key intermediates>, HPLC of Formula: 1435-43-4, the main research area is dihalobenzene organolithium lithiation; haloaryl lithium preparation elimination; aryne preparation nucleophilic addition haloaryl lithium; halobiaryl preparation metal halogen exchange dicyclohexylchlorophosphorous; biaryl phosphine ligand preparation; aryl coupling reaction.

Upon treatment of various aryllithium intermediates with 1,2-dibromobenzene or 1-bromo-2-iodobenzene, dissym. ortho,ortho’-di-, tri- and even tetrasubstituted bromo- or iodobiaryls, e.g., I, become readily available. The crucial steps in all these reactions were the nucleophilic addition of the organolithium precursor to a transient aryne species released from it by β-elimination of a lithium halide and, stabilization of the resulting 2-biaryllithium intermediate by in situ transfer of bromine or iodine from the starting material. This straightforward transition metal-free access to biaryls allows the preparation of highly valuable halobiaryls on a gram scale in excellent yields. These precursors can be subsequently functionalized by highly regioselective halogen/metal permutations into a vast variety of target mols. This was demonstrated in the synthesis of several mono- and diphosphine ligands, e.g., II.

Advanced Synthesis & Catalysis published new progress about Alkynes, arynes Role: FMU (Formation, Unclassified), FORM (Formation, Nonpreparative). 1435-43-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H3ClF2, HPLC of Formula: 1435-43-4.

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

Walby, Grant D.; Martin, Stephen F. published the artcile< Preparation of novel analogs of 2-arylpiperidines and evaluation of their sigma receptor binding affinities>, Safety of (E)-Cinnamoyl chloride, the main research area is arylpiperidine preparation mol docking sigma receptor binding affinity; Binding affinities and selectivities; Computational docking; Scaffold simplification; Sigma receptors; Synthesis.

A number of substituted norbenzomorphans was previously identified as high affinity ligands for the two known sigma receptors σ1R and σ2R/TMEM97, and some norbenzomorphans that were selective for σ2R/TMEM97 exhibited promise in animal models of several neurol. disorders. Toward further assessing the effects of simplifying the norbenzomorphan scaffold, sets of 6-membered heterocycles were designed and prepared, and their binding affinities for σ1R and σ2R/TMEM97 were determined Consistent with the design strategy, N-acyl-2-arylpiperidines showed high affinity for σ2R/TMEM97, whereas those derived from morpholine and N-methylpiperazine had lower affinities. However, most of these 6-membered heterocycles unexpectedly exhibited even higher affinity for σ1R and were thus σ1R-selective. Computational docking studies showed that representative 6-membered heterocycles bind and interact with σ2R/TMEM97 in a manner similar to that of a docked structure of their norbenzomorphan parent. Collectively, these binding and computational studies supported our design strategy for developing simplified analogs of norbenzomorphans as σ2R/TMEM97 ligands, but they also underscore the challenges associated with developing selective modulators of σ2R/TMEM97.

European Journal of Medicinal Chemistry published new progress about Buchwald-Hartwig reaction. 17082-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H7ClO, Safety of (E)-Cinnamoyl chloride.

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

Hu, Ming-Hao; Lin, Jia-Hong published the artcile< New Dibenzoquinoxalines Inhibit Triple-Negative Breast Cancer Growth by Dual Targeting of Topoisomerase 1 and the c-MYC G-Quadruplex>, SDS of cas: 27841-33-4, the main research area is dibenzoquinoxaline preparation breast cancer topoisomerase 1 MYC quadruplex inhibitor.

As c-MYC is one of the central players in triple-neg. breast cancer (TNBC) oncogenesis, inhibiting c-MYC expression would be an effective anticancer strategy. Transcription-induced neg. supercoiling is crucial in the regulation of c-MYC transcription, which facilitates the formation of a G4 structure in NHE III1 that can silence the transcription. However, topoisomerase 1 (Topo1) can dissipate this neg. supercoiling, leading to continuous activation of c-MYC transcription. Thus, dual ligands targeting both Topo1 and c-MYC G4 appear to be significant in cancer therapy. In this study, a series of new dibenzoquinoxaline derivatives were designed, synthesized, and evaluated for both Topo1 and c-MYC inhibition. Among them, 11-Methoxy-3,6-bis(4-methylpiperazin-1-yl)dibenzo[a,c]-phenazine was identified as the most promising dual ligand, which could effectively inhibit Topo1 activity and strongly stabilize c-MYC G4, thereby inhibiting cancer cell growth. Accordingly, this work suggests that this dual-targeting strategy may be effective in cancer therapy.

Journal of Medicinal Chemistry published new progress about Animal gene, c-myc Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 27841-33-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H12N2O2, SDS of cas: 27841-33-4.

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

Sui, Yan-Fei; Ansari, Mohammad Fawad; Zhou, Cheng-He published the artcile< Pyrimidinetrione-imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation>, Quality Control of 611-19-8, the main research area is imidazolylmethylene pyrimidinetrione preparation antifungal antibacterial cytotoxicity mol docking SAR; Antifungal; DNA; Imidazole; Membrane; Pyrimidinetrione.

A series of pyrimidinetrione-imidazole conjugates I [R1 = H, Et, 2-chlorobenzl, etc.] as potentially antifungal agents were developed. Bioassays manifested that I [R1 = 4-fluorobenzl] exerted favorable inhibition towards C. albicans (MIC=0.002 mM), being 6.5 folds more active than clin. antifungal drug fluconazole (MIC=0.013 mM). Preliminary mechanism research indicated that compound I [R1 = 4-fluorobenzl] could not only depolarize membrane potential but also permeabilize the membrane of C. albicans. Mol. docking was operated to simulate the interaction mode between mol. I [R1 = 4-fluorobenzl] and CYP51. In addition, hybrid I [R1 = 4-fluorobenzl] might form I [R1 = 4-fluorobenzl]-DNA supramol. complex via intercalating into DNA. The interference of membrane and DNA might contributed to its fungicidal capacity with no obvious tendency to induce the resistance against C. albicans. Conjugate I [R1 = 4-fluorobenzl] endowed good blood compatibility as well as low cytotoxicity towards HeLa and HEK-293T cells.

Chemistry – An Asian Journal published new progress about Antibacterial agents. 611-19-8 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2, Quality Control of 611-19-8.

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

He, Piao; Liu, Jiahao; Wu, Jinting; Mei, Haozheng; Zhang, Jianguo published the artcile< Dimethoxycarbonyl Groups Surrounding a Symmetric Diaminobistetrazole Ring: Exploring New Green Energetic Materials>, Computed Properties of 128-09-6, the main research area is energetic material methoxycarbonyl aminobistetrazole synthesis; sodium methoxycarbonyl aminobistetrazolate energetic material synthesis; DFT calculations; detonation performance; dimethoxycarbonyl diaminobistetrazole; energetic materials.

A novel oxygen-containing dimethoxycarbonyl diaminobistetrazole was synthesized via a facile strategy. The sodium salt based on this ligand was prepared and these two compounds were fully characterized by using elemental anal., IR and mass spectrometry and single-crystal X-ray diffraction. Their d., heats of formation, thermal stability, sensitivity, and the energetic properties are investigated by EXPLO5 code. These newly synthesized compounds possess high pos. heats of formation and detonation heats. the dimethoxycarbonyl diaminobistetrazole exhibits good detonation performance and acceptable stability, and might be a potential eco-friendly alternative of lead azide. The present study contributes to the development of tetrazole derivatives as new energetic materials.

Chemistry – An Asian Journal published new progress about Detonation enthalpy. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Computed Properties of 128-09-6.

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

Hao, Wenyan; Xu, Zhaotao; Zhou, Zebiao; Cai, Mingzhong published the artcile< Recyclable Heterogeneous Palladium-Catalyzed Cyclocarbonylation of 2-Iodoanilines with Acyl Chlorides in the Biomass-Derived Solvent 2-Methyltetrahydrofuran>, HPLC of Formula: 17082-09-6, the main research area is green palladium catalyzed cyclocarbonylation iodoaniline acyl chloride benzoxazinone synthesis.

A highly efficient, green palladium-catalyzed cyclocarbonylation of 2-iodoanilines with acyl chlorides has been developed that proceeds smoothly in a biomass-derived solvent 2-methyltetrahydrofuran with N,N-diisopropylethylamine as base at 100°C under 20 bar of carbon monoxide using an 2-aminoethylamino-modified MCM-41-anchored palladium acetate complex [2N-MCM-41-Pd(OAc)2] as a heterogeneous catalyst, yielding a wide variety of 2-substituted 4H-3,1-benzoxazin-4-one derivatives in good to excellent yields. This supported palladium catalyst could be facilely obtained by a two-step procedure from easily available starting materials and readily recovered via a simple filtration process and recycled at least 8 times without any apparent decrease in catalytic efficiency. The developed methodol. not only avoids the use of toxic solvents such as THF and DMF but also solves the basic problem of expensive palladium catalyst recovery and reuse and prevents effectively palladium contamination of the desired product.

Journal of Organic Chemistry published new progress about Acid chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 17082-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C9H7ClO, HPLC of Formula: 17082-09-6.

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

Sang, Dayong; Tian, Juan; Tu, Xiaodong; He, Zhoujun; Yao, Ming published the artcile< Cleavage of Catechol Monoalkyl Ethers by Aluminum Triiodide-Dimethyl Sulfoxide>, SDS of cas: 16766-30-6, the main research area is catechol preparation; monoalkyl ether catechol demethylation aluminum triiodide dimethyl sulfoxide.

Using eugenol and vanillin as model substrates, a practical method is developed for the cleavage o-hydroxyphenyl alkyl ethers. Aluminum oxide iodide (O=AlI), generated in situ from aluminum triiodide and DMSO, is the reactive ether cleaving species. The method is applicable to catechol monoalkyl ethers as well as normal Ph alkyl ethers for the removal of Me, Et, iso-Pr, and benzyl groups. A variety of functional groups such as alkenyl, allyl, amide, cyano, formyl, keto, nitro, and halogen are well tolerated under the optimum conditions. Partial hydrodebromination was observed during the demethylation of 4-bromoguaiacol, and was resolved using excess DMSO as an acid scavenger. This convenient and efficient procedure would be a practical tool for the preparation of catechols.

Synthesis published new progress about C-O bond cleavage. 16766-30-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H7ClO2, SDS of cas: 16766-30-6.

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