Category: imidazoles-derivatives

Begtrup, Mikael; Larsen, Peter published the artcile< Alkylation, acylation, and silyation of azoles>, Formula: C4H5BrN2, the main research area is azole alkylation solvent effect; acylation azole anion; silylation azole anion; methylation benzylation azole anion.

Performing alkylation, acylation, and silylation reactions in sep. deprotonation and nucleophilic displacement steps allows for better control of reaction conditions and facilitates problem handling in these processes. In the alkylation of azoles, the alkylating agents and solvents possess individual reaction capabilities which seem to be approx. additive. Monoalkylation occurs if the sum of the normalized reaction potentials is equal or larger than the pKa value of the azole. Dialkylation is avoided by keeping the sum of the normalized reaction potentials below the pKa value of the alkylazole. The applicability of these principles is demonstrated by the development of effective procedures for the methylation, benzylation, acetylation, methoxycarbonylation, and trimethylsilylation of azoles.

Acta Chemica Scandinavica published new progress about Acylation. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Formula: C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Patutina, Olga; Chiglintseva, Daria; Bichenkova, Elena; Gaponova, Svetlana; Mironova, Nadezhda; Vlassov, Valentin; Zenkova, Marina published the artcile< Dual miRNases for triple incision of miRNA target: design concept and catalytic performance>, Safety of 7H-Purin-2-amine, the main research area is microRNA21 microRNAR155 microRNA17a oligonucleotide peptide catalysis; RNA cleavage; RNase H; anti-miRNA therapy; artificial ribonuclease; miRNase; oligonucleotide-peptide conjugate; oncogenic miRNA.

Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiol. In 2017, for the first time we introduced miRNAses-miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we report the development of Dual miRNases against oncogenic miR-21, miR-155, miR-17 and miR-18a, each containing the catalytic peptide placed in-between two short miRNA-targeted oligodeoxyribonucleotide recognition motifs. Substitution of adenines with 2-aminoadenines in the sequence of oligonucleotide “”shoulders”” of the Dual miRNase significantly enhanced the efficiency of hybridization with the miRNA target. It was shown that sequence-specific cleavage of the target by miRNase proceeded metal-independently at pH optimum 5.5-7.5 with an efficiency varying from 15% to 85%, depending on the miRNA sequence. A distinct advantage of the engineered nucleases is their ability to addnl. recruit RNase H and cut miRNA at three different locations. Such cleavage proceeds at the central part by Dual miRNase, and at the 5′- and 3′-regions by RNase H, which significantly increases the efficiency of miRNA degradation Due to increased activity at lowered pH Dual miRNases could provide an addnl. advantage in acidic tumor conditions and may be considered as efficient tumor-selective RNA-targeted therapeutic.

Molecules published new progress about MicroRNA-155 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

De Bie, D. A.; Van Der Plas, H. C.; Geurtsen, G. published the artcile< Didehydrohetarenes. XX. Reactions of 4- and 5-haloimidazoles with lithium piperidide in piperidine>, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole, the main research area is halo imidazole lithium piperidide reaction.

On treatment of 5-halo-1-methyl-imidazole with lithium piperidide in piperidine, an addition-elimination reaction giving 1-methyl-5-piperidinoimidazole, transhalogenation giving 4-halo-1-methylimidazole and a meta substitution yielding the 1-methyl-2-piperidinoimidazole, were observed. No indication for the occurrence of a 4,5-didehydro-1-methylimidazole was obtained.

Recueil des Travaux Chimiques des Pays-Bas published new progress about 1003-21-0. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Lu, Zhongyang; Li, Yanchun; Syn, Wing-Kin; Wang, Zhewu; Lopes-Virella, Maria F.; Lyons, Timothy J.; Huang, Yan published the artcile< Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism>, Reference of 6823-69-4, the main research area is atherosclerosis nonalcoholic steatohepatitis amitriptyline antiatherosclerotic sphingolipid; acid sphingomyelinase; amitriptyline; diabetes; inflammation; nonalcoholic steatohepatitis.

We reported previously that increased acid sphingomyelinase (ASMase)-catalyzed hydrolysis of sphingomyelin, which leads to increases in ceramide and sphingosine 1 phosphate, played a key role in the synergistic upregulation of proinflammatory cytokines by palmitic acid (PA), a major saturated fatty acid, and lipopolysaccharide (LPS) in macrophages. Since macrophages are vital players in nonalcoholic steatohepatitis (NASH) and atherosclerosis, we assessed the effect of ASMase inhibition on NASH and atherosclerosis cooperatively induced by high-PA-containing high-fat diet (HP-HFD) and LPS in LDL receptor-deficient mice. Interestingly, immunohistochem. study showed that amitriptyline, but not GW4869, strongly reduced hepatic inflammation. Furthermore, results showed that both amitriptyline and GW4869 attenuated atherosclerosis. To elucidate the underlying mechanisms whereby amitriptyline inhibited both NASH and atherosclerosis, but GW4869 only inhibited atherosclerosis, we found that amitriptyline, but not GW4869, downregulated proinflammatory cytokines in macrophages. Finally, we found that inhibition of sphingosine 1 phosphate production is a potential mechanism whereby amitriptyline inhibited proinflammatory cytokines. Collectively, this study showed that amitriptyline inhibited NASH and atherosclerosis through modulation of sphingolipid metabolism in LDLR-/- mice, indicating that sphingolipid metabolism in macrophages plays a crucial role in the linkage of NASH and atherosclerosis.

American Journal of Physiology published new progress about Atherosclerosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Radhakrishnan, Harikrishnan; Javitz, Harold S.; Bhatnagar, Parijat published the artcile< Lentivirus Manufacturing Process for Primary T-Cell Biofactory Production>, Recommanded Product: 7H-Purin-2-amine, the main research area is FRalpha HDAC CAR T cell growth viral infection; CAR T cells; cell engineering; cell manufacturing; drug delivery; high-titer lentivirus production.

A process for maximizing the titer of lentivirus particles, deemed to be a necessity for transducing primary cells, is developed. Lentivirus particles, with a set of transgenes encoding an artificial cell-signaling pathway, are used to transform primary T cells as vectors for calibrated synthesis of desired proteins in situ, i.e., T-cell biofactory cells. The process is also used to generate primary T cells expressing antigen-specific chimeric antigen receptors, i.e., CAR T cells. The two differently engineered primary T cells are expanded and validated for their resp. functions, i.e., calibrated synthesis of desired proteins upon engaging the target cells, which is specific for the T-cell biofactory cells, and cytolysis of the target cells common to both types of cells. The process is compliant with current Good Manufacturing Practices and can be used to support the scale-up for clin. translation.

Advanced Biosystems published new progress about Biomarkers. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Khalil-Moghaddam, Shiva; Shahvelayati, Ashraf Sadat; Aliahmadi, Atousa published the artcile< Synthesis and antioxidant properties of two new derivatives of indeno-benzofuran>, Safety of 1-carboxymethyl-3-methylimidazolium chloride, the main research area is pyrogallol ninhydrin adduct preparation green chem antioxidant.

Ninhydrin reacts with poly-phenols in different ratios to produce tetracyclic adducts. Here, pyrogallol was used as a polyphenol compound In the company of acidic ionic liquid (AIL), there was a selective reaction between the ortho-site of polyphenol and the ninhydrin’s carbonyl group. Mono-adduct (1:1) and bis-adduct (2:1) were prepared using 1-(carboxymethyl)-3-methyl-1H-imidazolium chloride (mcmimCl) as a solvent and catalyst. Moreover, the antioxidant activity of these adducts was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay and butylated hydroxytoluene (BHT) was considered to be standard The results indicated that mono-adduct showed the strongest antioxidant activity (IC50 = 5.289μg/mL).

Journal of Chemical Health Risks published new progress about Antioxidants. 700370-07-6 belongs to class imidazoles-derivatives, and the molecular formula is C6H9ClN2O2, Safety of 1-carboxymethyl-3-methylimidazolium chloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ikezaki, Akira; Nakamura, Mikio published the artcile< Models for Cytochromes c': Spin States of Mono(imidazole)-Ligated (meso-Tetramesitylporphyrinato)iron(III) Complexes as Studied by UV-Vis, 13C NMR, 1H NMR, and EPR Spectroscopy>, HPLC of Formula: 36947-69-0, the main research area is cytochrome c model imidazole iron porphyrin complex; spin state imidazole iron porphyrin complex; ESR imidazole iron porphyrinato; solvent effect spin state imidazole iron porphinato; UV visible imidazole iron porphyrin complex; NMR chem shift imidazole iron porphyrin complex.

A number of mono(imidazole)-ligated complexes of (meso-tetramesitylporphyrinato)iron(III) perchlorate, [Fe(TMP)L]ClO4, were prepared, and their spin states were examined by 1H NMR, 13C NMR, and EPR spectroscopy as well as solution magnetic moments. All the complexes examined showed a quantum mech. spin admixed state of high and intermediate-spin (S = 5/2 and 3/2) states, though the contribution of the S = 3/2 state varies depending on the nature of axial ligands. While the complex with extremely bulky 2-tert-butylimidazole (2-tBuIm) has exhibited an essentially pure S = 5/2 state, the complex with electron-deficient 4,5-dichloroimidazole (4,5-Cl2Im) adopts an S = 3/2 state with 30% of the S = 5/2 spin admixture From the 1H and 13C NMR results, the S = 3/2 contribution at ambient temperature increases according to the following order: 2-tBuIm < 2-(1-EtPr)Im < 2-MeIm ≤ 2-EtIm ≤ 2-iPrIm < 4,5-Cl2Im. The effective magnetic moments determined by the Evans method in CH2Cl2 solution are 5.9 and 5.0 μB at 25° for [Fe(TMP)(2-tBuIm)]ClO4 and [Fe(TMP)(2-MeIm)]ClO4, resp., which further verify the order given above. Comparison of the NMR and EPR data revealed that the S = 3/2 contribution changes sensitively by the temperature; the S = 3/2 contribution decreases as the temperature is lowered for all the mono(imidazole) complexes examined The solvent polarity also affects the spin state; polar solvents such as MeOH and MeCN increase the S = 3/2 contribution while nonpolar solvents such as benzene decrease it. These results are explained in terms of the structurally flexible nature of the mono(imidazole) complexes; structural parameters such as the Fe(III)-Naxial bond length, displacement of the Fe from the N4 core, tilting of the Fe(III)-Naxial bond to the heme normal, orientation of the coordinated imidazole ligand, etc., could be altered by the nature of the axial ligands as well as by the solvent polarity and temperature Some mysteries on the spin states of cytochromes c' isolated from various bacterial sources are possibly explained in terms of the flexible nature of the mono(imidazole)-ligated structure. Inorganic Chemistry published new progress about ESR (electron spin resonance). 36947-69-0 belongs to class imidazoles-derivatives, and the molecular formula is C7H12N2, HPLC of Formula: 36947-69-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Zhen; Zhang, Yali; Pinkas, Daniel M.; Fox, Alice E.; Luo, Jinfeng; Huang, Huocong; Cui, Shengyang; Xiang, Qiuping; Xu, Tingting; Xun, Qiuju; Zhu, Dongsheng; Tu, Zhengchao; Ren, Xiaomei; Brekken, Rolf A.; Bullock, Alex N.; Liang, Guang; Ding, Ke; Lu, Xiaoyun published the artcile< Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2>, Safety of 5-Bromo-1-methyl-1H-imidazole, the main research area is design synthesis heterocycloalkynylbenzimide dual inhibitor Discoidin domain receptor; antiinflammatory drug discovery human pharmacokinetic mol modeling.

Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, I, tightly bound to DDR1 and DDR2 proteins with Kd values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, resp.; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 μM. DDR1- and DDR2-kinase inhibition by I was validated by Western-blotting anal. in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound I may serve as a lead compound for new anti-inflammatory drug discovery.

Journal of Medicinal Chemistry published new progress about Acute toxicity. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Safety of 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ren, Jing; Ding, Liang; Zhang, Dongya; Shi, Guoping; Xu, Qianyun; Shen, Sunan; Wang, Yaping; Wang, Tingting; Hou, Yayi published the artcile< Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19>, Electric Literature of 6823-69-4, the main research area is colorectal cancer fibroblast stemness chemoresistance lncRNA H19; CAFs; CRC; H19; chemoresistance; stemness.

In this study, we further investigated the underlying tumor-promoting roles of CAFs and the mol. mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed. SW480 cells with H19 stably knocked down were used to establish a xenograft model. The indicated protein levels in xenograft tumor tissues were confirmed by immunohistochem. assay, and cell apoptosis was analyzed by TUNEL apoptosis assay. The AldeRed ALDH detection assay was performed to detect intracellular aldehyde dehydrogenase (ALDH) enzyme activity. Results: H19 was highly expressed in the tumor tissues of CAC mice compared with the expression in normal colon tissues. Moreover, H19 was associated with the stemness of colorectal cancer stem cells (CSCs) in CRC specimens. Of note, H19 was enriched in CAF-derived conditioned medium and exosomes, which in turn promoted the stemness of CSCs and the chemoresistance of CRC cells in vitro and in vivo. Conclusion: CAFs promote the stemness and chemoresistance of CRC by transferring exosomal H19. H19 activated the β-catenin pathway via acting as a competing endogenous RNA sponge for miR-141, while miR-141 inhibited the stemness of CRC cells. Our findings indicate that H19 expressed by CAFs of the colorectal tumor stroma contributes to tumor development and chemoresistance.

Theranostics published new progress about Animal gene, HSP70 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Electric Literature of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Essandoh, Kobina; Yang, Liwang; Wang, Xiaohong; Huang, Wei; Qin, Dongze; Hao, Jiukuan; Wang, Yigang; Zingarelli, Basilia; Peng, Tianqing; Fan, Guo-Chang published the artcile< Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction>, Reference of 6823-69-4, the main research area is GW4869 exosome sepsis inflammation cardiac dysfunction; Cardiac dysfunction; Exosomes; Inflammatory response; Macrophages; Sepsis.

Sepsis is an infection-induced severe inflammatory disorder that leads to multiple organ failure. Amongst organs affected, myocardial depression is believed to be a major contributor to septic death. While it has been identified that large amounts of circulating pro-inflammatory cytokines are culprit for triggering cardiac dysfunction in sepsis, the underlying mechanisms remain obscure. Addnl., recent studies have shown that exosomes released from bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this study whether blocking the generation of exosomes would be protective against sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre-treated RAW264.7 macrophages with GW4869, an inhibitor of exosome biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected wild-type (WT) mice with GW4869 for 1 h prior to endotoxin treatment or cecal ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869 significantly impaired release of both exosomes and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac inflammation, attenuated myocardial depression and prolonged survival. Together, our findings indicate that blockade of exosome generation in sepsis dampens the sepsis-triggered inflammatory response and thereby, improves cardiac function and survival.

Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Bacterial infection. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem