Tag: M.W=500-550

Segura-Cabrera, Aldo published the artcileAn integrated network platform for contextual prioritization of drugs and pathways, 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 Molecular BioSystems (2015), 11(11), 2850-2859, database is CAplus and MEDLINE.

Repurposing of drugs to novel disease indications has promise for faster clin. translation. However, identifying the best drugs for a given pathol. context is not trivial. We developed an integrated random walk-based network framework that combines functional biomol. relationships and known drug-target interactions as a platform for contextual prioritization of drugs, genes and pathways. We show that the use of gene-centric or drug-centric data, such as gene expression data or a phenotypic drug screen, resp., within this network platform can effectively prioritize drugs and pathways, resp., to the studied biol. context. We demonstrate that various genomic data can be used as contextual cues to effectively prioritize drugs to the studied context, while similarly, phenotypic drug screen data can be used to effectively prioritize genes and pathways to the studied phenotypic context. As a proof-of-principle, we showcase the use of our platform to identify known and novel drug indications against different subsets of breast cancers through contextual prioritization based on genome-wide gene expression, shRNA and drug screen and clin. survival data. The integrated network and associated methods are incorporated into the NetWalker suite for functional genomics anal. (http://netwalkersuite.org).

Molecular BioSystems 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 C18H23N3O4S, 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

Cacciari, Barbara published the artcileA2A Adenosine Receptor Antagonists as Therapeutic Candidates: Are They Still an Interesting Challenge?, 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 Mini-Reviews in Medicinal Chemistry (2018), 18(14), 1168-1174, database is CAplus and MEDLINE.

A review. In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors, with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes, namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature and, moreover, of the pathophysiol. roles of all the adenosine receptor subtypes. In particular, the involvement of the A2A adenosine receptor subtype in some physiol. mechanisms in the brain, that could be related to important diseases such as the Parkinson′s disease, encouraged the research in this field. Particular attention was given to the antagonists endowed with high affinity and selectivity since they could have a real employment in the treatment of Parkinson′s disease, and some compounds, such as istradefylline, preladenant and tozadenant, are already studied in clin. trials. Actually, the role of A2A antagonists in Parkinson′s disease is becoming contradictory due to contrasting results in the last studies, but, at the same time, new possible employments are emerging for this class of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of A2A ligands.

Mini-Reviews in 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, 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

Hickey, Patrick published the artcileAdenosine A2A Antagonists in Parkinson’s Disease: What’s Next?, Application In Synthesis of 377727-87-2, the publication is Current Neurology and Neuroscience Reports (2012), 12(4), 376-385, database is CAplus and MEDLINE.

A review. Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, affecting up to 10 million people worldwide. Current treatment primarily involves symptom management with dopaminergic replacement therapy. Levodopa remains the most effective oral treatment, although long-term use is associated with complications such as wearing off, dyskinesias, and on-off fluctuations. Non-dopaminergic medications that improve PD symptoms and motor fluctuations are in demand. Adenosine A2A receptors are abundantly expressed within the basal ganglia and offer a unique target to modify abnormal striatal signaling associated with PD. Preclin. animal models have shown the ability of adenosine A2A receptor antagonists to improve PD motor symptoms, reduce motor fluctuations and dyskinesia, as well as protect against toxin-induced neuronal degeneration. Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. The safety and efficacy of this class of compounds continues to be defined and future studies should focus on non-motor symptoms, dyskinesias, and neuroprotection.

Current Neurology and Neuroscience Reports 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 In Synthesis of 377727-87-2.

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

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

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

Stocchi, Fabrizio published the artcileRandomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease, HPLC of Formula: 377727-87-2, the publication is Neurology (2017), 88(23), 2198-2206, database is CAplus and MEDLINE.

Objective: To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. Methods: This was a randomized, 26-wk, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving L-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3). Results: The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 wk. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a neg. difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11), and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%). Conclusions: No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results. Clin. trial registration: Clinicaltrials.gov: NCT01155479. Classification of evidence: This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

Neurology 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 C17H18N2O6, HPLC of Formula: 377727-87-2.

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

Tang, Yan-feng published the artcileSynthesis of preladenant, Product Details of C25H29N9O3, the publication is Jingxi Huagong (2014), 31(10), 1250-1254, database is CAplus.

An intermediate, 1-(4′-methoxyethoxyl phenyl) piperazine (III), was synthesized from 1-(4′-hydroxylphenyl)-piperazinyl ethanone (I) via etherification and hydrolysis. Another intermediate (VII) with a nitrogen condensed ring was prepared from Me furan-2-carboxylate (IV) by acylation, ring-closure and halogenation. Finally, Preladenant was prepared from the two intermediates by condensation reaction. FTIR, ¹HNMR and ESI-MS were employed to characterize these intermediates and the target compound Through common synthetic method, the yields of these 6 steps are 99.0%, 95.4%, 98.0%, 78.9%, 86.9% (calculated by Cl) and 52.5%, resp. To obtain a higher total yield, ultrasonic was used in the last condensation reaction. The results show that the condensation yield reached 85.4% when the reaction conditions were as follows: the ultrasonic power (150 W), the molar ratio of intermediate III to VII (1.2: 1), solvent (DMSO), acid-bonding agent (Na₂CO₃), reaction temperature (90°C) and reaction time (1.5 h). The yield of the condensation is greatly increased by ultrasonic method.

Jingxi Huagong 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 C44H28ClFeN4, Product Details of C25H29N9O3.

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

Neustadt, Bernard R. published the artcilePotent and selective adenosine A_2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines, Product Details of C25H29N9O3, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(3), 967-971, database is CAplus and MEDLINE.

Antagonism of the adenosine A_2a receptor offers great promise in the treatment of Parkinson’s disease. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A_2A antagonists, which led to clin. candidate SCH 420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective (vs A₁) A_2a antagonist activity, including oral activity in the rat haloperidol-induced catalepsy model. Structure-activity relationships and plasma levels are described for this series.

Bioorganic & Medicinal Chemistry Letters 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, Product Details of C25H29N9O3.

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