Tag: M.W=500-550

Eddy, Matthew T. published the artcileExtrinsic Tryptophans as NMR Probes of Allosteric Coupling in Membrane Proteins: Application to the A_2A Adenosine Receptor, HPLC of Formula: 377727-87-2, the publication is Journal of the American Chemical Society (2018), 140(26), 8228-8235, database is CAplus and MEDLINE.

Tryptophan indole ¹⁵N-¹H signals are well separated in NMR spectra of proteins. Assignment of the indole ¹⁵N-¹H signals therefore enables one to obtain site-specific information on complex proteins in supramacromol. systems, even when extensive assignment of backbone ¹⁵N-¹H resonances is challenging. Here the authors exploit the unique indole ¹⁵N-¹H chem. shift by introducing extrinsic tryptophan reporter residues at judiciously chosen locations in a membrane protein for increased coverage of structure and function by NMR. The authors demonstrate this approach with three variants of the human A_2A adenosine receptor (A_2AAR), a class A G protein-coupled receptor, each containing a single extrinsic tryptophan near the receptor intracellular surface, in helix V, VI, or VII, resp. The authors show that the native A_2AAR global protein fold and ligand binding activity are preserved in these A_2AAR variants. The indole ¹⁵N-¹H signals from the extrinsic tryptophan reporter residues show different responses to variable efficacy of drugs bound to the receptor orthosteric cavity, and the indole ¹⁵N-¹H chem. shift of the tryptophan introduced at the intracellular end of helix VI is sensitive to conformational changes resulting from interactions with a polypeptide from the carboxy terminus of the Gα_S intracellular partner protein. Introducing extrinsic tryptophans into proteins in complex supramol. systems thus opens new avenues for NMR investigations in solution

Journal of the American Chemical Society 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

Zhou, Xiaoyun published the artcileRadiation Dosimetry of a Novel Adenosine A_2A Receptor Radioligand [¹¹C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats, Formula: C25H29N9O3, the publication is Molecular Imaging and Biology (2017), 19(2), 289-297, database is CAplus and MEDLINE.

[11C]Preladenant was developed as a novel adenosine A2A receptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [11C]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomog. (PET)/x-ray computed tomog. (CT) imaging in rats. Procedures: Male Wistar rats (n = 35) were i.v. injected with [11C]preladenant. The tracer biodistribution was determined by organ harvesting at 1, 5, 15, 30, 60, and 90 min post injection. Hollow organs including the stomach, intestines, and urinary bladder were harvested with contents. In 10 rats, a 90-min dynamic PET/CT scan of the torso was acquired. Twenty volumes of interest (VOIs) were manually drawn on the PET image using the CT image of the same animal as anatomical reference The dynamic time-activity curves were used to calculate organ residence times (RTs). Human radiation dosimetry estimates, derived from rat data, were calculated with OLINDA/EXM 1.1. PET-imaging and organ-harvesting estimated comparable organ RTs, with differences of 6-27 %, except for the lungs, pancreas, and urinary bladder, with differences of 48, 53, and 60, resp. The critical organ was the small intestine with a dose of 25 μSv/MBq. The EDs (EDs) calculated from imaging-based and organ-harvesting-derived data were 5.5 and 5.6 μSv/MBq, resp., using the International Commission on Radiol. Protection 60 tissue weighting factors. The ED of [11C]preladenant (2 mSv for a 370-MBq injected dose) is comparable with other C-11-labeled PET tracers. Estimation of the radiation dosimetry of [11C]preladenant by PET/CT imaging in rats is feasible and gives comparable results to organ harvesting, provided that small VOIs are used and the content of hollow organs is taken into account. Dosimetry by PET imaging can strongly reduce the number of laboratory animals required.

Molecular Imaging and Biology 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 C5H6N2O2, Formula: C25H29N9O3.

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

Michel, Anne published the artcileUnprecedented therapeutic potential with a combination of A_2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson’s disease, Safety 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 PLoS One (2014), 9(12), e114086/1-e114086/25, 25 pp., database is CAplus and MEDLINE.

In Parkinson’s disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A_2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261 + Merck 22; Sch-58261 + Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug sep. and to determine whether any interaction between two drugs was additive or synergistic. Addnl. post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered sep. at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacol. interactions. The combined administration of A_2A/NR2B-receptor antagonists improved motor behavior in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.

PLoS One 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, Safety 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

Gyoneva, Stefka published the artcileSystemic inflammation regulates microglial responses to tissue damage in vivo., Synthetic Route of 377727-87-2, the publication is Glia (2014), 62(8), 1345-60, database is MEDLINE.

Microglia, the resident immune cells of the central nervous system, exist in either a “resting” state associated with physiological tissue surveillance or an “activated” state in neuroinflammation. We recently showed that ATP is the primary chemoattractor to tissue damage in vivo and elicits opposite effects on the motility of activated microglia in vitro through activation of adenosine A2A receptors. However, whether systemic inflammation affects microglial responses to tissue damage in vivo remains largely unknown. Using in vivo two-photon imaging of mice, we show that injection of lipopolysaccharide (LPS) at levels that can produce both clear neuroinflammation and some features of sepsis significantly reduced the rate of microglial response to laser-induced ablation injury in vivo. Under proinflammatory conditions, microglial processes initially retracted from the ablation site, but subsequently moved toward and engulfed the damaged area. Analyzing the process dynamics in 3D cultures of primary microglia indicated that only A2A , but not A1 or A3 receptors, mediate process retraction in LPS-activated microglia. The A2A receptor antagonists caffeine and preladenant reduced adenosine-mediated process retraction in activated microglia in vitro. Finally, administration of preladenant before induction of laser ablation in vivo accelerated the microglial response to injury following systemic inflammation. The regulation of rapid microglial responses to sites of injury by A2A receptors could have implications for their ability to respond to the neuronal death occurring under conditions of neuroinflammation in neurodegenerative disorders.

Glia 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, Synthetic Route of 377727-87-2.

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

Lu, Jing published the artcileAn anti-parkinson’s disease drug via targeting adenosine A2A receptor enhances amyloid-β Generation and γ-secretase activity, Application In Synthesis of 377727-87-2, the publication is PLoS One (2016), 11(11), e0166415/1-e0166415/21, database is CAplus and MEDLINE.

γ-Secretase mediates the intramembranous proteolysis of amyloid precursor protein (APP) and determines the generation of Aβ which is associated with Alzheimer’s disease (AD). Here we identified that an anti-Parkinson’s disease drug, Istradefylline, could enhance Aβ generation in various cell lines and primary neuronal cells of APP/PS1 mouse. Moreover, the increased generation of Aβ42 was detected in the cortex of APP/PS1 mouse after chronic treatment with Istradefylline. Istradefylline promoted the activity of γ-secretase which could lead to increased Aβ production These effects of Istradefylline were reduced by the knockdown of A2AR but independent of A2AR-mediated G protein- or β-arrestindependent signal pathway. We further observed that A2AR colocalized with γ-secretase in endosomes and phys. interacted with the catalytic subunit presenilin-1 (PS1). Interestingly, Istradefylline attenuated the interaction in time- and dosage-dependent manners. Moreover the knockdown of A2AR which in theory would release PS1 potentiated both Aβ generation and γ-secretase activity. Thus, our study implies that the association of A2AR could modulate γ-secretase activity. Istradefylline enhance Aβ generation and γ-secretase activity possibly via modulating the interaction between A2AR and γ-secretase, which may bring some undesired effects in the central nervous system (CNS).

PLoS One 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

Pinna, Annalisa published the artcileNeuroinflammation and L-dopa-induced abnormal involuntary movements in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease are counteracted by combined administration of a 5-HT_1A/1B receptor agonist and A_2A receptor antagonist, Quality Control of 377727-87-2, the publication is Neuropharmacology (2021), 108693, database is CAplus and MEDLINE.

Several lines of evidence have strongly implicated neuroinflammation in Parkinson’s disease (PD) progression and L-dopa-induced dyskinesia. The present study investigated whether early subchronic pretreatment with the serotonin 5-HT1A/1B receptor agonist eltoprazine plus the adenosine A_2A receptor antagonist preladenant counteracted L-dopa-induced abnormal involuntary movements (AIMs, index of dyskinesia), and neuroinflammation, in unilateral 6-hydroxydopamine(6-OHDA)-lesioned rat model of PD. The immunoreactivity of glial fibrillary acidic protein (GFAP), and the colocalization of ionized calcium binding adaptor mol.-1 (IBA-1), with interleukin (IL)-1β, tumor-necrosis-factor-αF (TNF-α) and IL-10 were evaluated in the denervated caudate-putamen (CPu) and substantia nigra pars-compacta (SNc). The combined subchronic pretreatment with L-dopa plus eltoprazine and preladenant reduced AIMs induced by acute L-dopa challenge in these rats and decreased GFAP and IBA-1 immunoreactivity induced by the drug in both CPu and SNc, with reduction in IL-1β in IBA-1-pos. cells in both CPu and SNc, and in TNF-α in IBA-1-pos. cells in SNc. Moreover, a significant increase in IL-10 in IBA-1-pos. cells was observed in SNc. Evaluation of immediate early-gene zif-268 (index of neuronal activation) after L-dopa challenge, showed an increase in its expression in denervated CPu of rats pretreated with L-dopa or L-dopa plus preladenant compared with vehicle, whereas rats pretreated with eltoprazine, with or without preladenant, had lower zif-268 expression. Finally, tyrosine hydroxylase and dopamine transporter examined to evaluate neurodegeneration, showed a significant equal decrease in all exptl. groups. The present findings suggest that combination of L-dopa with eltoprazine and preladenant may be promising therapeutic strategy for delaying the onset of dyskinesia, preserving L-dopa efficacy and reducing neuroinflammation markers in nigrostriatal system of 6-OHDA-lesioned rats.

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, Quality Control of 377727-87-2.

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

Du, Juan-juan published the artcileCurrent nondopaminergic therapeutic options for motor symptoms of Parkinson′s disease, Safety 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 Chinese Medical Journal (Beijing, China, English Edition) (2017), 130(15), 1856-1866, database is CAplus and MEDLINE.

The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson′s disease (PD). Papers in English published in PubMed, Cochrane, and Ovid Nursing databases between Jan. 1988 and Nov. 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clin. trials in the website of clinicaltrials.gov. Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review. PD is conventionally treated with dopamine replacement strategies, which are effective in the early stages of PD. Long-term use of levodopa could result in motor complications. Recent studies revealed that nondopaminergic systems such as adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator pathways could include potential therapeutic targets for motor symptoms, including motor fluctuations, levodopa-induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as istradefylline and amantadine, are currently used clin., while most such drugs are in preclin. testing stages. Transitioning of these agents into clin. beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite pos. findings at the preclin. level. Targeting nondopaminergic transmission could improve some motor symptoms in PD, especially the discomfort of dyskinesia. Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa, further investigation is required to ensure their success.

Chinese Medical Journal (Beijing, China, English 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, Safety 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

Hauser, Robert A. published the artcilePreladenant in patients with Parkinson’s disease and motor fluctuations: a phase 2, double-blind, randomised trial, Application In Synthesis of 377727-87-2, the publication is Lancet Neurology (2011), 10(3), 221-229, database is CAplus and MEDLINE.

Preladenant is an adenosine 2A (A_2A) receptor antagonist. In animal models of Parkinson’s disease, preladenant monotherapy improves motor function without causing dyskinesia and, as an adjunct to levodopa, it improves motor function without worsening dyskinesia. We aimed to assess the efficacy and safety of preladenant in patients with Parkinson’s disease and motor fluctuations who were receiving levodopa and other antiparkinsonian drugs. In this phase 2, dose-finding trial, patients with Parkinson’s disease who were receiving levodopa were enrolled and treated at 44 sites in 15 countries between Dec., 2006, and Nov., 2008. Assignment to treatment was done centrally with an interactive voice response system, according to a block randomisation schedule that was computer generated by the sponsor. Patients were assigned to receive 1, 2, 5, or 10 mg oral preladenant twice daily, or matching placebo for 12 wk. Patients, study staff, investigators, and all sponsor personnel were masked to treatment assignment. The primary outcome was change in mean daily off time from baseline to week 12, as assessed by home diaries. Efficacy anal. included all patients who received at least one dose of study drug and had data for assessments after baseline. This trial is registered with ClinicalTrials.gov, number NCT00406029. 253 Patients were randomised to receive preladenant (1 mg [n = 49], 2 mg [n = 49], 5 mg [n = 49], 10 mg [n = 57]) or placebo (n = 49), of whom 234 on preladenant (1 mg [n = 47], 2 mg [n = 48], 5 mg [n = 45], 10 mg [n = 49]) and placebo (n = 45) were eligible for the efficacy anal. Mean daily off time from baseline to week 12 was reduced vs. placebo in patients on 5 mg preladenant (difference -1.0 h, 95% CI -2.1 to 0.0; p = 0.0486) and 10 mg preladenant (-1.2 h, -2.2 to -0.2; p = 0.019). Changes in mean daily off time vs. placebo were not significant for 1 mg preladenant (0.2 h, -0.9 to 1.2; p = 0.753) or 2 mg preladenant (-0.7 h, -1.7 to 0.3; p = 0.162). The most common adverse events in the combined preladenant group vs. placebo were worsening of Parkinson’s disease (22 [11%] vs 4 [9%]), somnolence (20 [10%] vs 3 [6%]), dyskinesia (18 [9%] vs 6 [13%]), nausea (17 [9%] vs 5 [11%]), constipation (15 [8%] vs 1 [2%]), and insomnia (15 [8%] vs 4 [9%]). 5 and 10 mg preladenant twice daily might be clin. useful to reduce off time in patients with Parkinson’s disease and motor fluctuations. Funding: Schering-Plough, a subsidiary of Merck.

Lancet 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 C25H29N9O3, Application In Synthesis of 377727-87-2.

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

Jones, Carrie K. published the artcileThe metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson’s disease, Product Details of C25H29N9O3, the publication is Journal of Pharmacology and Experimental Therapeutics (2012), 340(2), 404-421, database is CAplus and MEDLINE.

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that pos. allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu₄), including N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclin. models of PD. However, these early mGlu₄ PAMs exhibited unsuitable physiochem. properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu₄ in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacol. characterization of a systemically active mGlu₄ PAM, N-(3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with L-DOPA or an adenosine 2A (A_2A) receptor antagonist currently in clin. development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of L-DOPA, suggesting that mGlu₄ PAMs may provide L-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu₄ PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either L-DOPA or A_2A antagonists.

Journal of Pharmacology and Experimental Therapeutics 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

Zhukov, Andrei published the artcileBiophysical Mapping of the Adenosine A_2A Receptor, Related Products of triazoles, the publication is Journal of Medicinal Chemistry (2011), 54(13), 4312-4323, database is CAplus and MEDLINE.

A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophys. Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, addnl. single mutations are then added at positions that could be involved in small mol. interactions. The StaR and a panel of binding site mutants are captured onto Biacore chips to enable characterization of the binding of small mol. ligands using surface plasmon resonance (SPR) measurement. A matrix of binding data for a set of ligands vs. each active site mutation is then generated, providing specific affinity and kinetic information (K_D, k_on, and k_off) of receptor-ligand interactions. This data set, in combination with mol. modeling and docking, is used to map the small mol. binding site for each class of compounds Taken together, the many constraints provided by these data identify key protein-ligand interactions and allow the shape of the site to be refined to produce a high quality three-dimensional picture of ligand binding, thereby facilitating structure based drug design. Results of biophys. mapping of the adenosine A_2A receptor are presented.

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 C25H47NO8, Related Products of triazoles.

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