Category: 377727-87-2

Saini, Anjali published the artcileAdenosine receptor antagonists: Recent advances and therapeutic perspective, 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 European Journal of Medicinal Chemistry (2022), 113907, database is CAplus and MEDLINE.

A review. Adenosine is an endogenous purine-based nucleoside expressed nearly in all body tissues. It regulates various body functions by activating four G-protein coupled receptors, A1, A2A, A2B, and A3. These receptors are widely acknowledged as drug targets for treating different neurol., metabolic, and inflammatory diseases. Although numerous adenosine receptor inhibitors have been developed worldwide, achieving target selectivity is still a big hurdle in drug development. However, the identification of specific radioligands-based affinity assay, fluorescent ligands, and MS-based ligand assay have contributed to the development of selective and potent adenosine ligands. In recent years various small heterocyclic-based mols. have shown some promising results. Istradefylline has been approved for treating Parkinson’s in Japan, while preladenant, tozadenant, CVT-6883, MRS-1523, and many more are under different phases of clin. development. The present review is focused on the quest to develop potent and selective adenosine inhibitors from 2013 to early 2021 by various research groups. The review also highlights their biol. activity, selectivity, structure-activity relationship, mol. docking, and mechanistic studies. A special emphsesis on drug designing strategies has been also given the manuscript. The comprehensive compilation of research work carried out in the field will provide inevitable scope for designing and developing novel adenosine inhibitors with improved selectivity and efficacy.

European 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, 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

Salem, Haitham published the artcileRevisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges, Category: triazoles, the publication is Current Neuropharmacology (2017), 15(5), 789-798, database is CAplus and MEDLINE.

A review. Background: Akathisia continues to be a significant challenge in current neurol. and psychiatric practice. Prompt and accurate detection is often difficult and there is a lack of consensus concerning the neurobiol. basis of akathisia. No definitive treatment has been established for akathisia despite numerous preclin. and clin. studies. Method: We reviewed antipsychotic-induced akathisia including its clin. presentation, proposed underlying pathophysiol., current and under investigation therapeutic strategies. Conclusion: Despite the initial promise that second generation antipsychotics would be devoid of akathisia effects, this has not been confirmed. Currently, there are limited therapeutic options for the clin. practice and the evidence supporting the most widely used treatments (beta blockers, anticholinergic drugs) is still absent or inconsistent.

Current Neuropharmacology 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, Category: triazoles.

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

Vala, Christine published the artcileSynthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A_2A Receptors, COA of Formula: C25H29N9O3, the publication is ChemMedChem (2016), 11(17), 1936-1943, database is CAplus and MEDLINE.

Imaging agents that target adenosine type 2A (A_2A) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson’s disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A_2A receptor d. and function in neurodegenerative diseases. We previously described the successful evaluation of two A_2A-specific radiotracers in both nonhuman primates and in subsequent human clin. trials: [¹²³I]MNI-420 and [¹⁸F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A_2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A_2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[¹⁸F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([¹⁸F]MNI-444) and 7-(2-(4-(2-fluoro-4-[¹²³I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([¹²³I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A_2A receptors in brain.

ChemMedChem 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 C5H10O2S, COA of Formula: C25H29N9O3.

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

Ishibashi, Kenji published the artcileOccupancy of adenosine A_2A receptors by istradefylline in patients with Parkinson’s disease using ¹¹C-preladenant PET, Product Details of C25H29N9O3, the publication is Neuropharmacology (2018), 106-112, database is CAplus and MEDLINE.

The present study aimed to calculate occupancy rates of A_2ARs by administrating istradefylline 20 mg or 40 mg, which is the currently approved dose for PD in Japan. Addnl., A_2AR availability was compared between patients with PD and healthy controls. Ten patients with PD under levodopa therapy and six age-matched healthy controls were included. The patients underwent a total of two ¹¹C-preladenant positron emission tomog. scans before and after the administration of istradefylline 20 mg or 40 mg (both n = 5). Binding potential (BP_ND) was calculated to estimate A_2AR availability in the ventral striatum, caudate, and putamen. Maximal A_2AR occupancy and ED₅₀ were estimated by modeling the dose-occupancy curves. All patients were around the middle stage of PD, and their characteristics were clin. heterogeneous. Maximal A_2AR occupancy and ED₅₀ were 93.5% and 28.6 mg in the ventral striatum, 69.5% and 10.8 mg in the caudate, and 66.8% and 14.8 mg in the putamen, resp. There were no significant differences in BP_ND values in the ventral striatum (P = 0.42), caudate (P = 0.72), and putamen (P = 0.43) between the PD and control groups. In conclusion, the present study shows that istradefylline binds to A_2ARs dose-dependently. A sufficient occupancy of A_2ARs could be obtained by administrating the approved dose of istradefylline.

Neuropharmacology 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

Sams, Anette Graven published the artcileHit-to-lead optimization of a series of carboxamides of ethyl 2-amino-4-phenylthiazole-5-carboxylates as novel adenosine A_2A receptor antagonists, COA of Formula: C25H29N9O3, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(17), 5241-5244, database is CAplus and MEDLINE.

Herein we describe the discovery of a series of novel adenosine A_2A receptor antagonists. A successful hit-to-lead optimization of an HTS hit led to replacement of a metabolically labile ester moiety with a heteroaromatic group. A compound from the series, (cyclopropanecarboxylic acid [5-(5-methyl-[1,2,4]oxadiazol-3-yl)-4-phenyl-thiazol-2-yl]-amide, compound 13), was shown to be effective in reversing haloperidol-induced hypolocomotion, a model of motor dysfunction in Parkinson’s Disease.

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, COA of Formula: C25H29N9O3.

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

Sams, Anette G. published the artcileDiscovery of Phosphoric Acid Mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A Phosphonooxymethylene Prodrug of a Potent and Selective hA2A Receptor Antagonist, HPLC of Formula: 377727-87-2, the publication is Journal of Medicinal Chemistry (2011), 54(3), 751-764, database is CAplus and MEDLINE.

The discovery and structure-activity relationship of a series of hA_2A receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson’s disease. It had acceptable ADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.

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, HPLC of Formula: 377727-87-2.

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

Zuniga-Ramirez, Carlos published the artcilePreladenant: an adenosine A_2A receptor antagonist for Parkinson’s disease, Category: triazoles, the publication is Future Neurology (2013), 8(6), 639-648, database is CAplus.

A review. Preladenant (SCH 420814) is a potent selective antagonist at the adenosine A_2A receptor that is being studied for treatment in early Parkinson’s disease (PD) as a monotherapy, and in moderate-to-severe PD as an add on to levodopa therapy. Unlike other drugs used for this disease, preladenant modulates adenosine action at the striatal level in order to block the inhibitory action of the basal ganglia output nuclei. Animal models of PD suggested that preladenant could be an effective treatment, which was further supported in a Phase II study of subjects with idiopathic PD who demonstrated a benefit in reducing off-time with an increase in on-time. In this article, we review current perspectives concerning pharmacol. approaches to PD, the pharmacol. properties of preladenant, its efficiency and safety, as well as the results reported for parkinsonian subjects treated with this drug.

Future 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 C20H19NO4, Category: triazoles.

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

Guney, Emre published the artcileNetwork-based in silico drug efficacy screening, HPLC of Formula: 377727-87-2, the publication is Nature Communications (2016), 10331, database is CAplus and MEDLINE.

The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug-disease proximity measure that quantifies the interplay between drugs targets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effect of drugs, as well as to distinguish palliative from effective treatments. Our anal. of 238 drugs used in 78 diseases indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugs used in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposing and the detection of adverse effects.

Nature Communications 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

Gyoneva, Stefka published the artcileAltered motility of plaque-associated microglia in a model of Alzheimer’s disease, Name: 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 Neuroscience (Amsterdam, Netherlands) (2016), 410-420, database is CAplus and MEDLINE.

Alzheimer’s disease (AD), the most common form of dementia in the elderly, is characterized by the presence of extracellular plaques composed of amyloid β (Aβ) peptides and intracellular tau aggregates. The plaques are surrounded by microglia, the brain’s resident immune cells, which likely participate in the clearance of Aβ by phagocytosis. The microglia that are associated with plaques display an abnormal ameboid morphol. and do not respond to tissue damage, in contrast to microglia in healthy brains. Here, we used time lapse confocal microscopy to perform a detailed real-time examination of microglial motility in acute hippocampal brain slices from the 5xFAD mouse model of AD, which was crossed to Cx3cr1^GFP/GFP mice to achieve microglia-specific GFP expression for visualization. During baseline conditions, microglia around plaques appeared hypermotile, moving the processes that were pointing away from plaques at higher speed than microglia not associated with plaques. Yet, neither plaque-associated, nor plaque-free microglia were able to extend processes toward sites of modest mech. damage. Application of the selective adenosine A2A receptor antagonist preladenant, which restores microglial response to cellular damage in a mouse model of Parkinson’s disease, reduced the hypermotility of plaque-associated microglia, but did not restore motility toward damaged cells in slices from 5xFAD mice. Our results suggest that process hypermotility and resistance to A2A antagonism during response to tissue damage may represent unique functional phenotypes of plaque-associated microglia that impair their ability to function properly in the AD brain.

Neuroscience (Amsterdam, Netherlands) 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, Name: 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