Month: October 2022

Boulton, B. E.; Coller, B. A. W. published the artcile< Kinetics, stoichiometry, and mechanism in the bromination of aromatic heterocycles. II. Aqueous bromination of imidazole, 1-methylimidazole, and 2-methylimidazole>, Name: 5-Bromo-1-methyl-1H-imidazole, the main research area is imidazole bromination kinetics.

The coulo-chrono-potentiometric method was used to obtain rate constants for reaction of Br with neutral imidazoles (aqueous, 298°K). Positional reactivities of imidazole and 1-methylimidazole decreased in the order 5 > 4 > 2. The 5-position of 2-methylimidazole was the most reactive site.

Australian Journal of Chemistry published new progress about Bromination kinetics. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Name: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Milner, Phillip J.; Yang, Yang; Buchwald, Stephen L. published the artcile< In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides [Erratum to document cited in CA163:458639]>, Product Details of C4H5BrN2, the main research area is erratum palladium catalyzed fluorination five membered heteroaryl bromide; bromoazole palladium catalyzed fluorination theor erratum.

An updated reference 15a is provided.

Organometallics published new progress about Crystal structure. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ilgu, Muslum; Yan, Shuting; Khounlo, Ryan M.; Lamm, Monica H.; Nilsen-Hamilton, Marit published the artcile< Common secondary and tertiary structural features of aptamer-ligand interaction shared by RNA aptamers with different primary sequences>, COA of Formula: C5H5N5, the main research area is secondary tertiary structural feature RNA aptamer ligand interaction; 2-aminopurine (2AP), molecular dynamics; aminoglycoside; isothermal titration calorimetry; neomycin-B RNA aptamer.

Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target mol. Here, we have combined computational and exptl. approaches to understand if aptamers with different sequences but the same mol. target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding. NEO2A was obtained from the same selection and, although they are only 43% identical in overall sequence, NEO1A and NEO2A share similar loop sequences. Exptl. anal. by 1D NMR and 2-aminopurine reporters combined with mol. dynamics modeling revealed similar structural and dynamical characteristics in both aptamers. These results are consistent with the hypothesis that the target ligand drives aptamer structure and also selects relevant dynamical characteristics for high-affinity aptamer-ligand interaction. Furthermore, they suggest that it might be possible to “”migrate”” structural and dynamical features between aptamer group members with different primary sequences but with the same target ligand.

Molecules published new progress about Affinity. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, COA of Formula: C5H5N5.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Choezom, Dolma; Gross, Julia Christina published the artcile< Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification>, Application In Synthesis of 6823-69-4, the main research area is SMPD3 extracellular vesicle V ATPase maturation; Endosomal cargo sorting; Endosomal maturation; Intraluminal vesicles; Secretory multivesicular bodies; Small extracellular vesicles.

During endosome maturation, neutral sphingomyelinase 2 (nSMase2, encoded by SMPD3) is involved in budding of intraluminal vesicles (ILVs) into late endosomes or multivesicular bodies (MVBs). Fusion of these with the plasma membrane results in secretion of exosomes or small extracellular vesicles (sEVs). Here, we report that nSMase2 activity controls sEV secretion through modulation of vacuolar H+-ATPase (V-ATPase) activity. Specifically, we show that nSMase2 inhibition induces V-ATPase complex assembly that drives MVB lumen acidification and consequently reduces sEV secretion. Conversely, we further demonstrate that stimulating nSMase2 activity with the inflammatory cytokine TNFα (also known as TNF) decreases acidification and increases sEV secretion. Thus, we find that nSMase2 activity affects MVB membrane lipid composition to counteract V-ATPase-mediated endosome acidification, thereby shifting MVB fate towards sEV secretion.

Journal of Cell Science published new progress about CD81 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tang, Ke; Roca, Jorjethe; Chen, Rong; Ansari, Anjum; Liang, Jie published the artcile< Thermodynamics of unfolding mechanisms of mouse mammary tumor virus pseudoknot from a coarse-grained loop-entropy model>, Category: imidazoles-derivatives, the main research area is mammary tumor virus pseudoknot thermodn entropy model; Energy landscape; Fluorescence spectroscopy; Heat capacity; Loop entropy; PK3D; Pseudoknotted RNA; RNA folding; RNA hairpin; Unfolding mechanism.

Pseudoknotted RNA mols. play important biol. roles that depend on their folded structure. To understand the underlying principles that determine their thermodn. and folding/unfolding mechanisms, we carried out a study on a variant of the mouse mammary tumor virus pseudoknotted RNA (VPK), a widely studied model system for RNA pseudoknots. Our method is based on a coarse-grained discrete-state model and the algorithm of PK3D (pseudoknot structure predictor in three-dimensional space), with RNA loops explicitly constructed and their conformational entropic effects incorporated. Our loop entropy calculations are validated by accurately capturing previously measured melting temperatures of RNA hairpins with varying loop lengths. For each of the hairpins that constitutes the VPK, we identified alternative conformations that are more stable than the hairpin structures at low temperatures and predicted their populations at different temperatures Our predictions were validated by thermodn. experiments on these hairpins. We further computed the heat capacity profiles of VPK, which are in excellent agreement with available exptl. data. Notably, our model provides detailed information on the unfolding mechanisms of pseudoknotted RNA. Anal. of the distribution of base-pairing probability of VPK reveals a cooperative unfolding mechanism instead of a simple sequential unfolding of first one stem and then the other. Specifically, we find a simultaneous “”loosening”” of both stems as the temperature is raised, whereby both stems become partially melted and co-exist during the unfolding process.

Journal of Biological Physics published new progress about Algorithm. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Kai-Bo; Dickerhoff, Jonathan; Wu, Guanhui; Yang, Danzhou published the artcile< PDGFR-β Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs>, Safety of 7H-Purin-2-amine, the main research area is vacancy G quadruplex PDGFRbeta promoter dGMP conformation guanine drug.

Aberrant expression of PDGFR-β is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-β gene promoter are transcriptional modulators and amenable to small mol. targeting. The major G4 formed in the PDGFR-β gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-β gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiol. relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-β vG4 in K+ solution This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic anal. elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3′- and 5′-end vG4s is present in the PDGFR-β promoter sequence, and dGMP favors the 5′-end fill-in. Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5′-vacancy, except for cGMP. CGMP binds both the 3′- and 5′-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiol. and pathol. processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-β vG4.

Journal of the American Chemical Society published new progress about Drugs. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Safety of 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Petrov, Viacheslav A.; Marshall, Will; Dooley, Rebecca published the artcile< One step synthesis of 1,3-dihydro-1-alkyl(aryl)-3-(hexafluoro-iso-propyl)-2H-imidazole-2-thiones>, Name: 5-Bromo-1-methyl-1H-imidazole, the main research area is tetrakistrifluoromethyldithietane reaction imidazole alkyl aryl; dithietane tetrakistrifluoromethyl reaction imidazole alkyl aryl; imidazolethione hexafluoroisopropyl preparation.

The reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (I) with variety of 1-alkyl- or 1-arylimidazoles led to the unexpected formation of 1,3-dihydro-1-alkyl(aryl)-3-(hexafluoroisopropyl)-2H-imidazole-2-thiones in 11-88% yields. The reaction proceeds in polar solvents such as DMF or DMSO leading to selective formation of the corresponding thiones which provide a simple one-step process for the preparation of these materials. While 1-alkylimidazoles rapidly react with I at ambient temperature, the reaction of 1-aryl- and 1-fluoralkylimidazoles requires higher temps and longer reaction times. Substituents in the 5-position of the imidazole ring hinder the reaction, but introduction of Me or Ph groups in the 5-position of imidazole totally blocked the formation of the corresponding thiones.

Journal of Fluorine Chemistry published new progress about Crystal structure. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Name: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Pilette, Charles published the artcile< Role of exosomes in allergic asthma: Signaling platforms between the epithelium and type 2 immunity>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is exosome allergic asthma signaling epithelium immunity; Asthma; Notch; contactin-1; type 2 immunity.

Exosomes activate (and are uptaken by) monocyte-derived, inflammatory dendritic cells (DCs) through contactin-1 and Notch2 activation, which in turn promotes TH2 cell-and TH17 cell-polarized immune activation along with mucus production and smooth muscle hyperresponsiveness. Airway epithelial cells release increased numbers of CD631 and CD811 exosomes following stimulation by house dust mite (HDM), a major allergen in allergic airway diseases such as rhinitis and asthma, and that those exosomes are also released in the bronchoalveolar lavage fluid from HDM-exposed mice. To address the role of these exosomes in the pathophysiol. of asthma, exosomes’ release by using GW4869, a noncompetitive inhibitor blocking exosome synthesis and/or release, which resulted in reduced recruitment of eosinophils in the bronchoalveolar lavage fluid from HDM-exposed and HDM-challenged mice. Airway tissue infiltration by inflammatory cells, mucus production, and levels of type 2 cytokines (IL-4, IL-5, and IL-13), as well as IFN-g levels but not IL-17A levels, were also downregulated.

Journal of Allergy and Clinical Immunology published new progress about Allergic asthma. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Schmitt, Christian; Kail, Dagmar; Mariano, Marica; Empting, Martin; Weber, Nadja; Paul, Tamara; Hartmann, Rolf W.; Engel, Matthias published the artcile< Design and synthesis of a library of lead-like 2,4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors>, Product Details of C4H5BrN2, the main research area is drug design bisheterocyclic thiophene Dyrk Clk inhibitor.

The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacol. inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as addnl. targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochem. properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacol. tool to dissect Dyrk2 isoform-mediated functions.

PLoS One published new progress about Cell proliferation. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Desage-El Murr, Marine; Cano, Celine; Golding, Bernard T.; Hardcastle, Ian R.; Hummersome, Marc; Frigerio, Mark; Curtin, Nicola J.; Menear, Keith; Richardson, Caroline; Smith, Graeme C. M.; Griffin, Roger J. published the artcile< 8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)>, Computed Properties of 1003-21-0, the main research area is biarylchromenone preparation inhibitor DNA dependent protein kinase; chromenone biaryl preparation inhibitor DNA dependent protein kinase.

The synthesis and biol. evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure-activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3-(thiophen-2-yl)phenyl)chromen-4-one and 8-(3-(thiophen-3-yl)phenyl)chromen-4-one being especially potent inhibitors.

Bioorganic & Medicinal Chemistry Letters published new progress about 1003-21-0. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Computed Properties of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem