Day: November 25, 2022

Wang, Wenya published the artcileDiscovery of highly potent novel antifungal azoles by structure-based rational design, Recommanded Product: 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(20), 5965-5969, database is CAplus and MEDLINE.

On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles were designed and synthesized. All the new azoles show excellent in vitro activity against most of the tested pathogenic fungi, which represent a class of promising leads for the development of novel antifungal agents. The MIC₈₀ value of compounds 8c, 8i and 8n against C. albicans is 0.001 μg/mL, indicating that these compounds are more potent than fluconazole, itraconazole and voriconazole. Flexible mol. docking was used to analyze the structure-activity relationships (SARs) of the compounds The designed compounds interact with CACYP51 through hydrophobic, van der Waals and hydrogen-bonding interactions.

Bioorganic & Medicinal Chemistry Letters published new progress about 86386-77-8. 86386-77-8 belongs to triazoles, auxiliary class Epoxides,Triazole,Fluoride,Salt,Sulfonic acid,Benzene, name is 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate, and the molecular formula is C2H5BF3K, Recommanded Product: 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Che, Xiaoying published the artcileNew azoles with potent antifungal activity: Design, synthesis and molecular docking, Formula: C12H13F2N3O4S, the publication is European Journal of Medicinal Chemistry (2009), 44(10), 4218-4226, database is CAplus and MEDLINE.

In response to the urgent need for novel antifungal agents with improved activity and broader spectrum, computer modeling was used for rational design of novel antifungal azoles. On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles with substituted-phenoxypropyl piperazine side chains were rationally designed and synthesized. In vitro antifungal activity assay indicates that the new azoles show good activity against most of the tested pathogenic fungi. Interestingly, the designed compounds are also active against an azole-resistant clin. strain. Compared to fluconazole and itraconazole, several compounds (such as I) show higher antifungal activity and a broader spectrum, which are promising leads for the development of novel antifungal agents.

European Journal of Medicinal Chemistry published new progress about 86386-77-8. 86386-77-8 belongs to triazoles, auxiliary class Epoxides,Triazole,Fluoride,Salt,Sulfonic acid,Benzene, name is 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate, and the molecular formula is C12H13F2N3O4S, Formula: C12H13F2N3O4S.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Blokhina, Svetlana V. published the artcileSynthesis and antifungal activity of new hybrids thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazole, SDS of cas: 86386-77-8, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 127944, database is CAplus and MEDLINE.

Fluconazole analogs substituted with thioxothiazolopyrimidinone moieties such as I were prepared as antifungal agents. The solubility and lipophilicity of the fluconazole analogs was determined Compounds with a methylpiperazinylalkyl linker exhibited significant antifungal activities against filamentous and yeast fungi.

Bioorganic & Medicinal Chemistry Letters published new progress about 86386-77-8. 86386-77-8 belongs to triazoles, auxiliary class Epoxides,Triazole,Fluoride,Salt,Sulfonic acid,Benzene, name is 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate, and the molecular formula is C12H13F2N3O4S, SDS of cas: 86386-77-8.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Gyoneva, Stefka published the artcileAdenosine A_2A receptor antagonism reverses inflammation-induced impairment of microglial process extension in a model of Parkinson’s disease, Recommanded Product: 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, the publication is Neurobiology of Disease (2014), 191-202, database is CAplus and MEDLINE.

Microglia, the immune cells of the central nervous system, constantly survey the parenchyma in the healthy brain to maintain homeostasis. When a disturbance, such as cell death, results in ATP release in vivo, microglial processes respond by utilizing P2Y₁₂ purinergic receptors to trigger extension toward the site of damage. Processes ultimately surround the injury site, preventing the spread of harmful cellular constituents and assisting with tissue repair. In contrast to the healthy brain, many neurodegenerative diseases, including Parkinson’s disease, are characterized by the presence of neuroinflammation. Yet, the ability of microglia to respond to tissue damage under pro-inflammatory conditions has not been well studied. To assess the ability of microglia to respond to tissue injury and localized cell death in the context of Parkinson’s disease, we performed confocal imaging of acute brain slices from mice with microglia-specific green fluorescent protein expression. Microglia in coronal slices containing the substantia nigra extend processes toward a mech. injury in a P2Y₁₂ receptor-dependent manner. However, microglia in mice treated for 5 days with 20 mg/kg/day 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show significantly reduced process displacement toward the injury compared to microglia in control animals. Pre-treatment of slices from MPTP-injected mice with the A_2A receptor-selective antagonist preladenant restores the ability of activated microglia to respond to tissue damage. These data support the hypothesis that chronic inflammation impedes microglial motility in response to further injury, such as cell death, and suggest that some aspects of the neuroprotection observed with adenosine A_2A receptor antagonists may involve direct or indirect actions at microglia.

Neurobiology of Disease published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Recommanded Product: 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Zhao, Kai-Yue published the artcileTuning Emission of AIE-Active Organometallic Ir(III) Complexes by Simple Modulation of Strength of Donor/Acceptor on Ancillary Ligands, Recommanded Product: 2-[5-(Trifluoromethyl)-1H-1,2,4-triazol-3-yl]pyridine, the publication is Organometallics (2016), 35(23), 3996-4001, database is CAplus.

A new design strategy to tune emission color of aggregation-induced emission (AIE) Ir(III) complexes, by simply adjusting the strength of donor/acceptor on ancillary ligands, is reported. Herein, all studied Ir(III) complexes employ 1-(2,4-difluorophenyl)-1H-pyrazole as cyclometalated ligands but different pyridine-1,2,4-triazolyl moieties as ancillary ligands that were modified with carbazole end-capped alkyl groups, in which pyridine-1,2,4-triazolyl moieties and functionalized carbazole act as donor and acceptor units, resp. The exptl. and theor. results clearly reveal the intrinsic relation between structures and emission behaviors. Enhancing the ability of donor and/or acceptor leads to red shifted emission and vice versa. One of the designed dyes exhibits the reversible and significant mechanochromic luminescent behavior thanks to its efficient AIE characteristic and structural modification, providing a feasible way to design multifunctional materials.

Organometallics published new progress about 219508-27-7. 219508-27-7 belongs to triazoles, auxiliary class Trifluoromethylated Building Blocks, name is 2-[5-(Trifluoromethyl)-1H-1,2,4-triazol-3-yl]pyridine, and the molecular formula is C15H12O6, Recommanded Product: 2-[5-(Trifluoromethyl)-1H-1,2,4-triazol-3-yl]pyridine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Zhilitskaya, L. V. published the artcileReaction of Imidazoles and Triazoles with 1-(Benzotriazol-1-yl)-2-iodoethanone, SDS of cas: 63598-71-0, the publication is Russian Journal of Organic Chemistry (2018), 54(10), 1531-1536, database is CAplus.

Reactions of 2-methyl-1H-imidazole, 1H-benzimidazole, 4H-1,2,4-triazole, and 1H-benzotriazole with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1-one in the absence of a base gave the corresponding N-mono- and N,N’-disubstituted derivatives 4H-1,2,4-Triazole-3-thiol reacted with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1-one to afford 1-([1,3]thiazolo[2,3-c][1,2,4]triazol-5-yl)-1H-benzotriazolium triiodide.

Russian Journal of Organic Chemistry published new progress about 63598-71-0. 63598-71-0 belongs to triazoles, auxiliary class Triazole, name is 4H-1,2,4-Triazole, and the molecular formula is C9H9NO6S, SDS of cas: 63598-71-0.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Stoessel, Anne published the artcileDual Targeting of Adenosine A_2A Receptors and Monoamine Oxidase B by 4H-3,1-Benzothiazin-4-ones, Related Products of triazoles, the publication is Journal of Medicinal Chemistry (2013), 56(11), 4580-4596, database is CAplus and MEDLINE.

Blockade of A_2A adenosine receptors (A_2AARs) and inhibition of monoamine oxidase B (MAO-B) in the brain are considered attractive strategies for the treatment of neurodegenerative diseases such as Parkinson’s disease (PD). In the present study, benzothiazinones, e.g., 2-(3-chlorophenoxy)-N-(4-oxo-4H-3,1-benzothiazin-2-yl)acetamide, were identified as a novel class of potent MAO-B inhibitors (IC₅₀ human MAO-B: 1.63 nM). Benzothiazinones with large substituents in the 2-position, e.g., methoxycinnamoylamino, phenylbutyrylamino, or chlorobenzylpiperazinylbenzamido residues, showed high affinity and selectivity for A_2AARs (K_i human A_2AAR: 39.5-69.5 nM). By optimizing benzothiazinones for both targets, the first potent, dual-acting A_2AAR/MAO-B inhibitors with a nonxanthine structure were developed. The best derivative was N-(4-oxo-4H-3,1-benzothiazin-2-yl)-4-phenylbutanamide (K_i human A_2A, 39.5 nM; IC₅₀ human MAO-B, 34.9 nM; selective vs. other AR subtypes and MAO-A), which inhibited A_2AAR-induced cAMP accumulation and showed competitive, reversible MAO-B inhibition. The new compounds may be useful tools for validating the A_2AAR/MAO-B dual target approach in PD.

Journal of Medicinal Chemistry published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C6H16OSi, Related Products of triazoles.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Sherbiny, Farag F. published the artcileHomology modelling of the human adenosine A_2B receptor based on x-ray structures of bovine rhodopsin, the β₂-adrenergic receptor and the human adenosine A_2A receptor, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, the publication is Journal of Computer-Aided Molecular Design (2009), 23(11), 807-828, database is CAplus and MEDLINE.

A three-dimensional model of the human adenosine A_2B receptor was generated by means of homol. modeling, using the crystal structures of bovine rhodopsin, the β₂-adrenergic receptor, and the human adenosine A_2A receptor as templates. In order to compare the three resulting models, the binding modes of the adenosine A_2B receptor antagonists theophylline, ZM241385, MRS1706, and PSB601 were investigated. The A_2A-based model was much better able to stabilize the ligands in the binding site than the other models reflecting the high degree of similarity between A_2A and A_2B receptors: while the A_2B receptor shares about 21% of the residues with rhodopsin, and 31% with the β₂-adrenergic receptor, it is 56% identical to the adenosine A_2A receptor. The A_2A-based model was used for further studies. The model included the transmembrane domains, the extracellular and the intracellular hydrophilic loops as well as the terminal domains. In order to validate the usefulness of this model, a docking anal. of several selective and nonselective agonists and antagonists was carried out including a study of binding affinities and selectivities of these ligands with respect to the adenosine A_2A and A_2B receptors. A common binding site is proposed for antagonists and agonists based on homol. modeling combined with site-directed mutagenesis and a comparison between exptl. and calculated affinity data. The new, validated A_2B receptor model may serve as a basis for developing more potent and selective drugs.

Journal of Computer-Aided Molecular Design published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C7H7ClN2, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Saidi-Idrissi, Malika published the artcileTheoretical and experimental study of protonation and deprotonation of 1,2,4-triazole and its C-substituted derivatives, Related Products of triazoles, the publication is Journal de Chimie Physique et de Physico-Chimie Biologique (1983), 80(10), 739-45, database is CAplus.

Semiempirical methods were used to study the structure of protonated and deprotonated triazoles. Monoprotonated triazoles exist in the 1,4 form. Vibrational spectra (4,000 to 200 cm^-1) are reported. From their anal., it is obvious that in the case of protonated systems, mol. association has only a small effect on ring vibrations. Triazoles give chelates with silver, not salts.

Journal de Chimie Physique et de Physico-Chimie Biologique published new progress about 63598-71-0. 63598-71-0 belongs to triazoles, auxiliary class Triazole, name is 4H-1,2,4-Triazole, and the molecular formula is C2H3N3, Related Products of triazoles.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Toyohara, Jun published the artcileTest-retest reproducibility of cerebral adenosine A_2A receptor quantification using [¹¹C]preladenant, Computed Properties of 377727-87-2, the publication is Annals of Nuclear Medicine (2022), 36(1), 15-23, database is CAplus and MEDLINE.

To evaluate the reproducibility of cerebral adenosine A_2A receptor (A_2AR) quantification using [¹¹C]preladenant ([¹¹C]PLN) and PET in a test-retest study. Eight healthy male volunteers were enrolled. Dynamic 90 min PET scans were performed twice at the same time of the day to avoid the effect of diurnal variation. Subjects refrained from caffeine from 12 h prior to scanning, and serum caffeine was measured before radioligand injection. Arterial blood was sampled repeatedly during scanning and the fraction of the parent compound in plasma was determined Total distribution volume (V_T) was estimated using 1- and 2-tissue compartment models (1-TCM and 2-TCM, resp.) and Logan graphical anal. (Logan plot) (t* = 30 min). Plasma-free fraction (f_P) of [¹¹C]PLN was measured and used for correction of V_T values. Distribution volume ratio (DVR) was calculated from V_T of target and reference regions and obtained by noninvasive Logan graphical reference tissue model (LGAR) (t* = 30 min). Absolute test-retest variability (aTRV), and intra-class correlation coefficient (ICC) of V_T and DVR were calculated as indexes of repeatability. Correlation between DVR and serum concentration of caffeine (a nonselective A_2AR blocker) was analyzed by Pearson′s correlation anal. Regional time-activity curves were well described by 2-TCM models. Estimation of V_T by 2-TCM produced some erroneous values; therefore, the more robust Logan plot was selected as the appropriate model. Global mean aTRV was 20% for V_T and 14% for V_T/f_P (ICC, 0.72 for V_T and 0.87 for V_T/f_P). Global mean aTRV of DVR was 13% for Logan plot and 10% for LGAR (ICC, 0.70 for Logan plot and 0.81 for LGAR). DVR estimates using LGAR and Logan plot were in good agreement (r² = 0.96). Coefficients of variation for V_T, V_T/f_P, DVR (Logan plot), and DVR (LGAR) were 47%, 47%, 27%, and 18%, resp. Despite low serum caffeine levels, significant concentration-dependent effects on [¹¹C]PLN binding to target regions were observed (p < 0.01). In this study, moderate test-retest reproducibility and large inter-subject differences were observed with [¹¹C]PLN PET, possibly attributable to competition by baseline amount of caffeine. Anal. of plasma caffeine concentration is recommended during [¹¹C]PLN PET studies.

Annals of Nuclear Medicine published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C12H10FeO4, Computed Properties of 377727-87-2.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics