Tag: M.W=500-550

Zhou, Gang published the artcileDiscovery of aminoquinazoline derivatives as human A_2A adenosine receptor antagonists, 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 Bioorganic & Medicinal Chemistry Letters (2016), 26(4), 1348-1354, database is CAplus and MEDLINE.

Novel bicyclic adenosine A_2A antagonists with an aminoquinazoline moiety were designed and synthesized. The optimization of the initial lead compound based on in vitro and in vivo activity has led to the discovery of a potent and selective class of adenosine A_2A antagonists. The structure-activity relationships of this novel series of bicyclic aminoquinazoline derivatives as adenosine A_2A antagonists are described in detail.

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 C21H18N4OS, 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

Orru, Marco published the artcileStriatal pre- and postsynaptic profile of adenosine A_2A receptor antagonists, SDS of cas: 377727-87-2, the publication is PLoS One (2011), 6(1), e16088, database is CAplus and MEDLINE.

Striatal adenosine A_2A receptors (A_2ARs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D₂ receptors (D₂Rs). A_2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A₁ receptors (A₁Rs). It was hypothesized that postsynaptic A_2AR antagonists should be useful in Parkinson’s disease, while presynaptic A_2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington’s disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A_2AR antagonists may be subdivided according to a preferential pre- vs. postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical elec. stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, resp. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, resp., while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A_2AR-D₂R and A₁R-A_2AR heteromers to determine possible differences in the affinity of these compounds for different A_2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A_2AR when co-expressed with D₂R than with A₁R. KW-6002 showed the best relative affinity for A_2AR co-expressed with D₂R than co-expressed with A₁R, which can at least partially explain the postsynaptic profile of this compound Also, the in vitro pharmacol. profile of MSX-2, SCH-420814, ZM-241385, and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential pre- vs. postsynaptic actions, SCH-442416 and KW-6002 may be used as lead compounds to obtain more effective antidyskinetic and antiparkinsonian compounds, resp.

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, SDS of cas: 377727-87-2.

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

Hodgson, Robert A. published the artcilePreladenant, a selective A_2A receptor antagonist, is active in primate models of movement disorders, Product Details of C25H29N9O3, the publication is Experimental Neurology (2010), 225(2), 384-390, database is CAplus and MEDLINE.

Parkinson’s Disease (PD) and Extrapyramidal Syndrome (EPS) are movement disorders that result from degeneration of the dopaminergic input to the striatum and chronic inhibition of striatal dopamine D₂ receptors by antipsychotics, resp. Adenosine A_2A receptors are selectively localized in the basal ganglia, primarily in the striatopallidal (“indirect”) pathway, where they appear to operate in concert with D₂ receptors and have been suggested to drive striatopallidal output balance. In cases of dopaminergic hypofunction, A_2A receptor activation contributes to the overdrive of the indirect pathway. A_2A receptor antagonists, therefore, have the potential to restore this inhibitor imbalance. Consequently, A_2A receptor antagonists have therapeutic potential in diseases of dopaminergic hypofunction such as PD and EPS. Targeting the A_2A receptor may also be a way to avoid the issues associated with direct dopamine agonists. Recently, preladenant was identified as a potent and highly selective A_2A receptor antagonist, and has produced a significant improvement in motor function in rodent models of PD. Here we investigate the effects of preladenant in two primate movement disorder models. In MPTP-treated cynomolgus monkeys, preladenant (1 or 3 mg/kg; PO) improved motor ability and did not evoke any dopaminergic-mediated dyskinetic or motor complications. In Cebus apella monkeys with a history of chronic haloperidol treatment, preladenant (0.3-3.0 mg/kg; PO) delayed the onset of EPS symptoms evoked by an acute haloperidol challenge. Collectively, these data support the use of preladenant for the treatment of PD and antipsychotic-induced movement disorders.

Experimental 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, Product Details of C25H29N9O3.

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

Hodgson, Robert A. published the artcileCharacterization of the potent and highly selective A_2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression, 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 Journal of Pharmacology and Experimental Therapeutics (2009), 330(1), 294-303, database is CAplus and MEDLINE.

The adenosine A_2A receptor has been implicated in the underlying biol. of various neurol. and psychiatric disorders, including Parkinson’s disease (PD) and depression. Preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] are potent competitive antagonists of the human A_2A receptor (K_i = 1.1 and 0.6 nM, resp.) and have > 1000-fold selectivity over all other adenosine receptors, making these compounds the most selective A_2A receptor antagonists reported to date. Both compounds attenuate hypolocomotion induced by the A_2A receptor agonist CGS-21680 [2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamidoadenosine], suggesting that they inhibit A_2A receptor activity in vivo. Their high degree of selectivity and robust in vivo activity make preladenant and SCH 412348 useful tools to investigate the role of the A_2A receptor system in animal models of PD and depression. Oral administration of preladenant and SCH 412348 (0.1-1 mg/kg) to rats potentiated 3,4-dihydroxy-L-phenylalanine (L-Dopa)-induced contralateral rotations after 6-hydroxydopamine lesions in the medial forebrain bundle and potently attenuated the cataleptic effects of haloperidol. Preladenant (1 mg/kg) inhibited L-Dopa-induced behavioral sensitization after repeated daily administration, which suggests a reduced risk of the development of dyskinesias. Finally, preladenant and SCH 412348 exhibited antidepressant-like profiles in models of behavioral despair, namely the mouse tail suspension test and the mouse and rat forced swim test. These studies demonstrate that preladenant and SCH 412348 are potent and selective A_2A receptor antagonists and provide further evidence of the potential therapeutic benefits of A_2A receptor inhibition in PD (with reduced risk of dyskinesias) and depression (one of the primary nonmotor symptoms of PD).

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, 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

Zhou, Xiaoyun published the artcileIn vivo evaluation of 11C-preladenant for PET imaging of adenosine A2A receptors in the conscious monkey, Quality Control of 377727-87-2, the publication is Journal of Nuclear Medicine (2017), 58(5), 762-768, database is CAplus and MEDLINE.

Regional uptake of 11C-preladenant was consistent with the distribution of A2ARs in the monkey brain, with the highest uptake in the putamen, followed by the caudate, and the lowest uptake in the cerebellum. Tracer kinetics were well described by the 2-tissue-compartment model with a lower constraint on k4 to stabilize fits. The highest VT was observed in A2AR-rich regions (∼5.8-7.4) and lowest value in the cerebellum (∼1.3). BPND values estimated from the SRTM with different scan durations were comparable and were in agreement with DVR-1 (∼4.3-5.3 in A2AR-rich regions). Preladenant preinjection decreased the tracer uptake in A2AR-rich regions to the level of the reference regions. Caffeine pretreatment reduced the tracer uptake in the striatum in a dose-dependent manner. 11C-preladenant PET is suitable for noninvasive quantification of A2ARs and assessment of A2AR occupancy in A2AR-rich regions in the monkey brain. SRTM using the cerebellum as the reference tissue is the applicable model for A2AR quantification.

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 C13H12BClO3, Quality Control of 377727-87-2.

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

Kaltenbach, Linda S. published the artcileComposite primary neuronal high-content screening assay for Huntington’s disease incorporating non-cell-autonomous interactions, Related Products of triazoles, the publication is Journal of Biomolecular Screening (2010), 15(7), 806-819, database is CAplus and MEDLINE.

Huntington’s disease (HD) is a fatal neurodegenerative disease characterized by progressive cognitive, behavioral, and motor deficits and caused by expansion of a polyglutamine repeat in the Huntingtin protein (Htt). Despite its monogenic nature, HD pathogenesis includes obligatory non-cell-autonomous pathways involving both the cortex and the striatum, and therefore effective recapitulation of relevant HD disease pathways in cell lines and primary neuronal monocultures is intrinsically limited. To address this, the authors developed an automated high-content imaging screen in high-d. primary cultures of cortical and striatal neurons together with supporting glial cells. Cortical and striatal neurons are transfected sep. with different fluorescent protein markers such that image-based high-content anal. can be used to assay these neuronal populations sep. but still supporting their intercellular interactions, including abundant synaptic interconnectivity. This assay was reduced to practice using transfection of a mutant N-terminal Htt domain and validated via a screen of ∼400 selected small mols. Both expected as well as novel candidate targets for HD emerged from this screen; of particular interest were target classes with close relative proximity to clin. testing. These findings suggest that composite primary cultures incorporating increased levels of biol. complexity can be used for high-content imaging and “high-context” screening to represent mol. targets that otherwise may be operant only in the complex tissue environment found in vivo during disease pathogenesis.

Journal of Biomolecular Screening 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, Related Products of triazoles.

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

Hesk, D. published the artcileSynthesis of ³H, ²H₄, and ¹⁴C-MK 3814 (preladenant), 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 Labelled Compounds and Radiopharmaceuticals (2017), 60(4), 194-199, database is CAplus and MEDLINE.

MK 3814 is a potent and selective antagonist of the A_2a receptor. A_2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labeled forms of MK 3814 were synthesized. [³H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [¹⁴C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [²H₄]MK 3814 was prepared as an internal standard for a liquid chromatog. mass spectrometry bioanal. method. This paper discusses the synthesis of 3 isotopically labeled forms of MK 3814.

Journal of Labelled Compounds and Radiopharmaceuticals 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

Navarro, Gemma published the artcilePurinergic signaling in Parkinson’s disease. Relevance for treatment, 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 Neuropharmacology (2016), 161-168, database is CAplus and MEDLINE.

A review. Purinergic signaling modulates dopaminergic neurotransmission in health and disease. Classically adenosine A₁ and A_2A receptors have been considered key for the fine tune control of dopamine actions in the striatum, the main CNS motor control center. The main adenosine signaling mechanism is via the cAMP pathway but the future will tell whether calcium signaling is relevant in adenosinergic control of striatal function. Very relevant is the recent approval in Japan of the adenosine A_2A receptor antagonist, istradefylline, for use in Parkinson’s disease patients. Purine nucleotides are also regulators of striatal dopamine neurotransmission via P2 purinergic receptors. In parallel to the alpha-synuclein hypothesis of Parkinson’s disease etiol., purinergic P2X₁ receptors have been identified as mediators of accumulation of the Lewy-body enriched protein alpha-synuclein. Of note is the expression in striatum of purinergic-receptor-containing heteromers that are potential targets of anti-Parkinson’s disease therapies and should be taken into account in drug discovery programs.

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, 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

Hagenow, Stefanie published the artcileAdenosine A_2AR/A₁R Antagonists Enabling Additional H₃R Antagonism for the Treatment of Parkinson’s Disease, Synthetic Route of 377727-87-2, the publication is Journal of Medicinal Chemistry (2021), 64(12), 8246-8262, database is CAplus and MEDLINE.

Adenosine A₁/A_2A receptors (A₁R/A_2AR) represent targets in nondopaminergic treatment of motor disorders such as Parkinson’s disease (PD). As an innovative strategy, multitargeting ligands (MTLs) were developed to achieve comprehensive PD therapies simultaneously addressing comorbid symptoms such as sleep disruption. Recognizing the wake-promoting capacity of histamine H₃ receptor (H₃R) antagonists in combination with the “caffeine-like effects” of A₁R/A_2AR antagonists, we designed A₁R/A_2AR/H₃R MTLs, where a piperidino-/pyrrolidino(propyloxy)phenyl H₃R pharmacophore was introduced with overlap into an adenosine antagonist arylindenopyrimidine core. These MTLs showed distinct receptor binding profiles with overall nanomolar H₃R affinities (K_i < 55 nM). Compound 4 (ST-2001, K_i (A₁R) = 11.5 nM, K_i (A_2AR) = 7.25 nM) (I) and 12 (ST-1992, K_i (A₁R) = 11.2 nM, K_i (A_2AR) = 4.01 nM) (II) were evaluated in vivo. L-DOPA-induced dyskinesia was improved after administration of compound 4 (1 mg kg^-1, i.p. rats). Compound 12 (2 mg kg^-1, p.o. mice) increased wakefulness representing novel pharmacol. tools for PD therapy.

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, Synthetic Route of 377727-87-2.

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