Category: Triazoles

Szaboo, Nikoletta published the artcileNovel therapy in Parkinson’s disease: adenosine A_2A receptor antagonists, HPLC of Formula: 377727-87-2, the publication is Expert Opinion on Drug Metabolism & Toxicology (2011), 7(4), 441-455, database is CAplus and MEDLINE.

A review. Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder. To date, most of the currently available therapies in PD target the dopaminergic system and none of these therapeutic approaches have been proven to modify the course of the disease. To various extents, these drugs can also cause motor and non-motor complications. A novel target, the adenosine A_2A receptor (AA2AR), was recently identified, blockade of which may alleviate Parkinsonian symptoms, reduce motor fluctuations and potentially afford neuroprotection. Areas covered: This review is based on a PubMed search covering the relationship of the adenosine receptors and PD. The role of the AA2AR is reviewed and the results of preclin. investigations of antagonists are assessed. A synopsis of current drug development is provided, with a special focus on the pharmacokinetics and relevant clin. trials. Expert opinion: The localization of the AA2AR in the central nervous system, the ultra structural localization and the mol. mechanism of its action reveal the potential importance of the AA2AR in movement disorders. The theor. background and exptl. data indicate that AA2AR antagonists may have a potential therapeutic effect in Parkinson’s disease. More importantly, the putative neuroprotective effect needs further investigation.

Expert Opinion on Drug Metabolism & Toxicology 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 C8H6ClF3, HPLC of Formula: 377727-87-2.

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

Comeo, Eleonora published the artcileSubtype-Selective Fluorescent Ligands as Pharmacological Research Tools for the Human Adenosine A_2A Receptor, Computed Properties of 377727-87-2, the publication is Journal of Medicinal Chemistry (2020), 63(5), 2656-2672, database is CAplus and MEDLINE.

Among class A G protein-coupled receptors (GPCR), the human adenosine A_2A receptor (hA_2AAR) remains an attractive drug target. However, translation of A_2AAR ligands into the clinic has proved challenging and an improved understanding of A_2AAR pharmacol. could promote development of more efficacious therapies. Subtype-selective fluorescent probes would allow detailed real-time pharmacol. investigations both in vitro and in vivo. In the present study, two families of fluorescent probes were designed around the known hA_2AAR selective antagonist preladenant (SCH 420814). Both families of fluorescent antagonists retained affinity at the hA_2AAR, selectivity over all other adenosine receptor subtypes and allowed clear visualization of specific receptor localization through confocal imaging. Furthermore, the Alexa Fluor 647-labeled conjugate allowed measurement of ligand binding affinities of unlabeled hA_2AAR antagonists using a bioluminescence resonance energy transfer (NanoBRET) assay. The fluorescent ligands developed here can therefore be applied to a range of fluorescence-based techniques to further interrogate hA_2AAR pharmacol. and signaling.

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 C25H29N9O3, Computed Properties of 377727-87-2.

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

Gareev, G. A. published the artcileReaction of some derivatives of 2-nitro-2-azapropanol with azoles, Category: triazoles, the publication is Zhurnal Organicheskoi Khimii (1988), 24(10), 2221-6, database is CAplus.

Treatment of triazoles and tetrazoles with nitroazapropanol derivatives MeN(NO₂)CH₂X [X = OAc (I), O₂CCF₃, or Cl] afforded N-substituted 2-nitro-2-azapropylazoles. Thus, reaction of 4-substituted tetrazole with I in THF or HCCl₃ (or neat) in the presence H₂SO₄ afforded alkylation products II (R = H, Ph, Me, CH₂:CH, CH₂:CMe, CF₃).

Zhurnal Organicheskoi Khimii published new progress about 84406-63-3. 84406-63-3 belongs to triazoles, auxiliary class Triazole,Nitro Compound, name is 4-Nitro-2H-1,2,3-triazole, and the molecular formula is C2H2N4O2, Category: triazoles.

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

Verkhozina, O. N. published the artcileSynthesis of Polynuclear Nonfused Azoles, Safety of 5-Nitro-1H-1,2,3-triazole, the publication is Russian Journal of Organic Chemistry (Translation of Zhurnal Organicheskoi Khimii) (2003), 39(12), 1792-1796, database is CAplus.

Polynuclear blocks consisting of nonfused heterocycles of the azole series, connected through methylene bridges, were synthesized by successive addition of azole units via cycloaddition of organic azides to the triple bond of N-(2-propynyl)azoles, as well as via reaction of azide ion at the cyano group of cyanomethylazoles. Initial N-(2-propynyl)azoles were prepared by reaction of 2-propynyl bromide with 1,2,3-triazoles, benzotriazole, and tetrazoles; cyanomethylazoles were obtained by alkylation of azoles with chloroacetonitrile. An analogous scheme was used to add heterocyclic units to 2-phenyl-1,2,3-triazole-4-carbonitrile. In this case, the 1st two heterocyclic units are linked through the ring C atom. For example, 5-phenyl-2-(tetrazol-5-ylmethyl)tetrazole was prepared from NaN₃ and (5-phenyl-2-tetrazolyl)acetonitrile, the latter of which was prepared from 5-phenyl-2H-tetrazole and chloroacetonitrile.

Russian Journal of Organic Chemistry (Translation of Zhurnal Organicheskoi Khimii) published new progress about 14544-45-7. 14544-45-7 belongs to triazoles, auxiliary class Triazoles, name is 5-Nitro-1H-1,2,3-triazole, and the molecular formula is C24H29N5O3, Safety of 5-Nitro-1H-1,2,3-triazole.

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

Claff, Tobias published the artcileSingle Stabilizing Point Mutation Enables High-Resolution Co-Crystal Structures of the Adenosine A_2A Receptor with Preladenant Conjugates, Computed Properties of 377727-87-2, the publication is Angewandte Chemie, International Edition (2022), 61(22), e202115545, database is CAplus and MEDLINE.

The G protein-coupled adenosine A_2A receptor (A_2AAR) is an important new (potential) drug target in immuno-oncol., and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A_2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A_2AAR have been solved, mostly using the A_2A-StaR2 protein that bears 9 point mutations, co-crystallization with Preladenant derivatives has so far been elusive. We developed a new A_2AAR construct harboring a single point mutation (S91^3.39K) which renders it extremely thermostable. This allowed the co-crystallization of two novel Preladenant derivatives, the polyethylene glycol-conjugated (PEGylated) PSB-2113, and the fluorophore-labeled PSB-2115. The obtained crystal structures (2.25 S and 2.6 S resolution) provide explanations for the high potency and selectivity of Preladenant derivatives They represent the first crystal structures of a GPCR in complex with PEG- and fluorophore-conjugated ligands. The applied strategy is predicted to be applicable to further class A GPCRs.

Angewandte Chemie, International Edition 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, Computed Properties of 377727-87-2.

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

Pinna, Annalisa published the artcileAntidyskinetic effect of A_2A and 5HT_1A/1B receptor ligands in two animal models of Parkinson’s disease, 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 Movement Disorders (2016), 31(4), 501-511, database is CAplus and MEDLINE.

Background : The serotonin 5-HT_1A/1B receptor agonist eltoprazine suppressed dyskinetic-like behavior in animal models of Parkinson’s disease (PD) but simultaneously reduced levodopa (L-dopa)-induced motility. Moreover, adenosine A_2A receptor antagonists, such as preladenant, significantly increased L-dopa efficacy in PD without exacerbating dyskinetic-like behavior. Objectives : We evaluated whether a combination of eltoprazine and preladenant may prevent or suppress L-dopa-induced dyskinesia, without impairing L-dopa’s efficacy in relieving motor signs, in 2 PD models: unilateral 6-hydroxydopamine-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Methods : Rotational behavior and abnormal involuntary movements, or disability and L-dopa-induced dyskinesia were evaluated in 6-hydroxydopamine-lesioned rats and MPTP-treated monkeys, resp. Moreover, in the rodent striatum, induction of immediate-early gene zif-268, an index of long-term changes, was correlated with dyskinesia. Results : In 6-hydroxydopamine-lesioned rats, combined administration of L-dopa (4 mg/kg) plus eltoprazine (0.6 mg/kg) plus preladenant (0.3 mg/kg) significantly prevented or reduced dyskinetic-like behavior without impairing motor activity. Zif-268 was increased in the striatum of rats treated with L-dopa and L-dopa plus preladenant compared with vehicle. In contrast, rats treated with eltoprazine (with or without preladenant) had lower zif-268 activation after chronic treatment in both the dyskinetic and L-dopa-non-primed groups. Moreover, acute L-dopa plus eltoprazine plus preladenant prevented worsening of motor performance (adjusting step) and sensorimotor integration deficit. Similar results were obtained in MPTP-treated monkeys, where a combination of preladenant with eltoprazine was found to counteract dyskinesia and maintain the full therapeutic effects of a low dose of L-dopa. Conclusions : Our results suggest a promising nondopaminergic pharmacol. strategy for the treatment of dyskinesia in PD. cpr 2016 International Parkinson and Movement Disorder Society.

Movement Disorders 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, 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

Grishkevich-Trokhimovskii, E. published the artcileThe action of nitrous acid on the nitrile of aminomalonic acid. II. Structure of dicyanotriazole, Synthetic Route of 53817-16-6, the publication is J. Russ. Phys.-Chem. Soc. (1924), 551-3, database is CAplus.

The white modification of II (above) obtained by sublimation near the m. p., remains white when recrystallized from Et₂O, turning yellow when crystallized from H₂O. Attempts to disclose a difference in structure by preparing derivatives of either modification were frustrated. With CH₂N₂ at 0° both were converted to the same methyldicyanotriazole, any mol. rearrangement being excluded at so low a temperature Saponification of II with 10% aqueous NaOH at 70° produces monocyanotriazolecarboxylic acid, m. 215-6° (decomposition); Ag salt, white cheese-like precipitate At a higher concentration and temperature II is converted to monoaminotriazolecarboxylic acid. C₄N₅Me saponified with strong H₂SO₄ gave acid (IV), m. 202.5-3.5°, from whose Ag salt with Mel was obtained the Me ester (V), m. 66-7°. Me ester (VI) of triazoledicarboxylic acid, prepared by this method, m. 83.5-84°; a mixture of V and VI m. 55-60°. Conclusion: the Me group of IV is attached to N, therefore, also in C₄N₅Me. The investigation is being continued.

J. Russ. Phys.-Chem. Soc. published new progress about 53817-16-6. 53817-16-6 belongs to triazoles, auxiliary class Triazoles, name is 1H-1,2,3-Triazole-4,5-dicarbonitrile, and the molecular formula is C4HN5, Synthetic Route of 53817-16-6.

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

Sakata, Muneyuki published the artcileInitial evaluation of an adenosine A2A receptor ligand, 11C-preladenant, in healthy human subjects, HPLC of Formula: 377727-87-2, the publication is Journal of Nuclear Medicine (2017), 58(9), 1464-1470, database is CAplus and MEDLINE.

11C-preladenant is a selective antagonist for mapping of cerebral adenosine A2A receptors (A2ARs) by PET. This is a first-in-human study to examine the safety, radiation dosimetry, and brain imaging of 11C-preladenant in healthy human subjects. Dynamic 11C-preladenant PET scans (90 min) were obtained in 5 healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined For anat. coregistration, T1-weighted MRI was performed. The total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1T and 2T, resp.). The distribution volume ratio (DVR) was calculated from VT of target and reference region and obtained with a noninvasive Logan graphical reference tissue method (t* = 30 min). The applicability of a shortened protocol as an alternative to the 90-min PET scan was investigated. Tracer biodistribution and dosimetry were determined in 3 healthy male subjects, using serial whole-body PET scans acquired over 2 h after 11C-preladenant injection. There were no serious adverse events in any of the subjects throughout the study period. 11C-preladenat readily entered the brain, with a peak uptake in the putamen and head of the caudate nucleus 30-40 min after tracer injection. Other brain regions showed rapid clearance of radioactivity. The regional distribution of 11C-preladenant was consistent with known A2AR densities in the brain. At pseudoequil. (reached at 40 min after injection), stable target-to-cerebellar cortex ratios of around 3.8-10.0 were obtained. The 2T fit better than the 1T in the low-d. A2AR regions. In contrast, there were no significant differences between 1T and 2T in the high-A2AR-d. regions. DVRs in the putamen and head of the caudate nucleus were around 3.8-10.3 when estimated using a Logan graphical reference tissue method with cerebellum as the reference region. PET scanning at 50 or 70 min can provide the stable DVR estimates within 10% or 5% differences at most, resp. The radioactivity was mainly excreted through the hepatobiliary system after 11C-preladenant injection. As a result, the absorbed dose (μy/MBq) was highest in the gallbladder wall (mean ± SD, 17.0 ± 2.5) and liver (11.7 ± 2.1). The estimated ED for 11C-preladenant was 3.7 ± 0.4 μSv/MBq. This initial evaluation indicated that 11C-preladenat is suitable for imaging of A2ARs in the brain.

Journal 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 C25H29N9O3, HPLC of Formula: 377727-87-2.

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

Matulis, Vadim E. published the artcileTheoretical study of gas-phase formation enthalpies and isomerism for 4(5)-nitro-1,2,3-triazole and its N-alkyl derivatives and experimental determination of formation enthalpy for 2-methyl-4-nitro-1,2,3-triazole, SDS of cas: 14544-45-7, the publication is Journal of Molecular Structure: THEOCHEM (2008), 854(1-3), 18-25, database is CAplus.

The formation enthalpies of tautomeric forms of 1,2,3-triazole, 4(5)-nitro-1,2,3-triazole and isomeric N-alkyl-4(5)-nitro-1,2,3-triazoles (alkyl = Me, Et, iso-Pr and tert-butyl) have been calculated with the d. functional theory B3LYP method by means of designed isolobal, isodesmic and isomerization reactions. The exptl. ideal-gas formation enthalpy of 2-methyl-4-nitro-1,2,3-triazole has been determined based on the formation enthalpy in the crystalline state and the sublimation enthalpy. The exptl. value of formation enthalpy (228.7 ± 3.5 kJ mol^-1) is in good agreement with the one obtained from reaction enthalpy calculations (233.5 kJ mol^-1). The relative Gibbs energies for tautomeric forms of 1,2,3-triazole and 4(5)-nitro-1,2,3-triazole and isomeric N-alkyl-4(5)-nitro-1,2,3-triazoles in aqueous solution have also been calculated using the Conductor polarized continuum model (CPCM). The results of the calculations have been discussed concerning the relative stability of the titled compounds

Journal of Molecular Structure: THEOCHEM published new progress about 14544-45-7. 14544-45-7 belongs to triazoles, auxiliary class Triazoles, name is 5-Nitro-1H-1,2,3-triazole, and the molecular formula is C2H2N4O2, SDS of cas: 14544-45-7.

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

Fukushima, Kazuaki published the artcileNatural bond orbital analysis of pericyclic and pseudopericyclic 1,5-electrocyclizations of conjugated nitrileimines, Synthetic Route of 63598-71-0, the publication is Bulletin of the Chemical Society of Japan (2004), 77(9), 1671-1679, database is CAplus.

Ab initio and DFT studies have revealed that there are three mechanisms in 1,5-electrocyclizations of conjugated nitrileimines. The first one is a pericyclic 1,5-electrocyclization of vinyl or (Z)-imino nitrileimine. Interactions between π-orbitals at C1 and X5 lead to formation of σC1-X5 bonds. The second one is a typical pseudopericyclic 1,5-electrocyclization of formyl nitrileimine. Nucleophilic interaction of lone pair electrons at O5 to π*C1-N2(h) leads to formation of a σC1-O5 bond. The natural bond orbital (NBO) anal. for the reaction has shown that there are two disconnections of orbital interactions at C1 and O5 at the transition state because of the orthogonal array of the forming σC1-O5 bond and the other π-orbitals. The third one is an incomplete pseudopericyclic 1,5-electrocyclization of (E)-imino nitrileimine. Nucleophilic interactions of lone pair electrons at N5 to π*C1-N2(h) and π*C1-N2(v) lead to formation of a σC1-N5 bond. There is a single disconnection of orbital interactions at N5 at the transition state, because the forming σC1-N5 bond and the other π-orbitals are orthogonal at N5 but not at C1, owing to twisting in the nitrileimine moiety.

Bulletin of the Chemical Society of Japan 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, Synthetic Route of 63598-71-0.

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