Day: November 25, 2022

Hauser, Robert A published the artcilePreladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned., 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 JAMA neurology (2015), 72(12), 1491-500, database is MEDLINE.

IMPORTANCE: Preladenant is an adenosine 2A receptor antagonist that reduced “off” time in a placebo-controlled phase 2b trial in patients with Parkinson disease (PD). We sought to confirm its efficacy in phase 3 trials. OBJECTIVE: To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS: Two 12-week, phase 3, randomized, placebo-controlled, double-blind trials performed from July 15, 2010, to April 16, 2013. The setting included neurology clinics, clinical research centers, and hospitals in the Americas, the European Union, Eastern Europe, India, and South Africa. Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations. INTERVENTIONS: In trial 1, a total of 778 eligible patients were randomized to the addition of preladenant (2 mg, 5 mg, or 10 mg twice daily), placebo, or rasagiline mesylate (1 mg/d) in a 1:1:1:1:1 ratio. In trial 2, a total of 476 eligible patients were randomized to the addition of preladenant (2 mg or 5 mg twice daily) or placebo in a 1:1:1 ratio. MAIN OUTCOMES AND MEASURES: The primary outcome measure was change in off time from baseline to week 12. RESULTS: In trial 1, neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.10 hour (95% CI, -0.69 to 0.46 hour) for preladenant 2 mg twice daily, -0.20 hour (95% CI, -0.75 to 0.41 hour) for preladenant 5 mg twice daily, -0.00 hour (95% CI, -0.62 to 0.53 hour) for preladenant 10 mg twice daily, and -0.30 hour (95% CI, -0.90 to 0.26 hour) for rasagiline mesylate 1 mg/d. In trial 2, preladenant was not superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.20 hour (95% CI, -0.72 to 0.35 hour) for preladenant 2 mg twice daily and -0.30 hour (95% CI, -0.86 to 0.21 hour) for preladenant 5 mg twice daily. Preladenant was well tolerated, with the most common adverse event that showed an increase over placebo in both trials being constipation (6%-8% for preladenant vs 1%-3% for placebo). CONCLUSIONS AND RELEVANCE: In these phase 3 trials, preladenant did not significantly reduce off time compared with placebo. That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01155466 and NCT01227265.

JAMA 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, 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

Maw, Graham N. published the artcileThe discovery of small molecule inhibitors of neutral endopeptidase. Structure-activity studies on functionalized glutaramides, Product Details of C2H2N4O2, the publication is Chemical Biology & Drug Design (2006), 67(1), 74-77, database is CAplus and MEDLINE.

A series of small mol. glutaramides were synthesized and evaluated for potency against canine and human neutral endopeptidase using target criteria of mol. weight <400 and log P between 2 and 4.5 to maximize the likelihood of achieving good oral absorption. The activity of a prototype compound, chiral (2R)-2-[[1-[[(5-ethyl-1,3,4-thiadiazol-2-yl)amino]carbonyl]cyclopentyl]methyl]pentanoic acid was reported. The structure-activity relationship (SAR) investigations described in this paper led to the identification of an Et 1,3,4-thiadiazole glutaramide which demonstrated good neutral endopeptidase potency, selectivity and excellent oral absorption in the rat.

Chemical Biology & Drug Design 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, Product Details of C2H2N4O2.

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

Man, Yanli published the artcileDegradation of difenoconazole in water and soil: Kinetics, degradation pathways, transformation products identification and ecotoxicity assessment, Category: triazoles, the publication is Journal of Hazardous Materials (2021), 126303, database is CAplus and MEDLINE.

Difenoconazole is a widely used triazole fungicide that has been frequently detected in the environment, but comprehensive study about its environmental fate and toxicity of potential transformation products (TPs) is still lacking. Here, laboratory experiments were conducted to investigate the degradation kinetics, pathways, and toxicity of transformation products of difenoconazole. 12, 4 and 4 TPs generated by photolysis, hydrolysis and soil degradation were identified via UHPLC-QTOF/MS and the UNIFI software. Four intermediates TP295, TP295A, TP354A and TP387A reported for the first time were confirmed by purchase or synthesis of their standards, and they were further quantified using UHPLC-MS/MS in all tested samples. The main transformation reactions observed for difenoconazole were oxidation, dechlorination and hydroxylation in the environment. ECOSAR prediction and laboratory tests showed that the acute toxicities of four novel TPs on Brachydanio rerio, Daphnia magna and Selenastrum capricornutum are substantially lower than that of difenoconazole, while all the TPs except for TP277C were predicted chronically very toxic to fish, which may pose a potential threat to aquatic ecosystems. The results are important for elucidating the environmental fate of difenoconazole and assessing the environmental risks, and further provide guidance for scientific and reasonable use.

Journal of Hazardous Materials published new progress about 136815-80-0. 136815-80-0 belongs to triazoles, auxiliary class Triazoles, name is 1-(2-Chloro-4-(4-chlorophenoxy)phenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one, and the molecular formula is C16H11Cl2N3O2, Category: triazoles.

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

Hu, Lu published the artcileEnergetic compounds based on a new fused triazolo[4,5-d]pyridazine ring: Nitroimino lights up energetic performance, Related Products of triazoles, the publication is Chemical Engineering Journal (Amsterdam, Netherlands) (2021), 420(Part_1), 129839, database is CAplus.

A series of highly energetic materials with good detonation performance, high d. and low impact sensitivity based on a new triazolo[4,5-d]pyridazine fused ring was synthesized and characterized. 4-Nitroamino-7-nitroimino-triazolo[4,5-d]pyridazine was characterized by single crystal X-ray structure anal., which shows that the proton of one nitroamino group was transferred to the pyridazine ring forming a nitroimino moiety. The electrostatic potential (ESP) of 4-Nitroamino-7-nitroimino-triazolo[4,5-d]pyridazine shows the nitroimino group has the lowest neg. value, while the nitroamino area has a high pos. value. The anal. of NCI plots indicates strong intramol. hydrogen bonds (HB) and π-π interactions which arise from the newly formed nitroimino group. This supports that the rearrangement of the nitroamino group to form the nitroimino moiety lowers the impact sensitivity. Compound 4-Nitroamino-7-nitroimino-triazolo[4,5-d]pyridazine·H₂O exhibits face-to-face packing, which gives rise to a relatively high d. of 1.87 g cm^-3 and a low impact sensitivity of 18 J. Its hydrazinium and hydroxylammonium salts have high detonation velocities of 9351 m s^-1 and 9307 m s^-1, resp. Their impact and friction sensitivities (7 J, 120 N and 8 J, 160 N) are similar to HMX. This proclivity for rearrangement by a nitroamino group provides new insight into the design of next generation high energy d. materials.

Chemical Engineering Journal (Amsterdam, Netherlands) 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, Related Products of triazoles.

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

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

Zhao, Qingjie published the artcileSynthesis of α-(2,4-difluorophenyl)-α-(1H-1,2,4-triazol-1-ylmethyl)-1-piperidineethanol analogs and derivatives and determination of their activity as antifungal agents, SDS of cas: 86386-77-8, the publication is Zhongguo Yaowu Huaxue Zazhi (2006), 16(3), 150-153, database is CAplus.

To study the effect of triazole derivatives with a side chain containing a 4-substituted-1-piperidinyl groups or a similar secondary amine on the antifungal activity of triazole compounds, nine title compounds were synthesized and determined by elementary anal., ¹H-NMR and IR spectra. An example compound thus prepared was α-(2,4-difluorophenyl)-α-(1H-1,2,4-triazol-1-ylmethyl)-1-piperidineethanol. The MICs of all the title compounds were determined by a method recommended by the national committee for clin. laboratory standards (NCCLS) using the RPMI 1640 test medium. All of the title compounds displayed potent antifungal activities to some extent. The activity of the two compounds were more than 4 times as high as that of fluconazole and itraconazole against Candida albicans in vitro. The stereochem. had important influence on the antifungal activities of the title compounds (no data).

Zhongguo Yaowu Huaxue Zazhi published new progress about 86386-77-8. 86386-77-8 belongs to triazoles, auxiliary class Epoxides,Triazole,Fluoride,Salt,Sulfonic acid,Benzene, name is 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole methanesulfonate, and the molecular formula is C13H12BClO3, SDS of cas: 86386-77-8.

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

Guerret, Olivier published the artcile1,2,4-Triazole-3,5-Diylidene: A Building Block for Organometallic Polymer Synthesis, Category: triazoles, the publication is Journal of the American Chemical Society (1997), 119(28), 6668-6669, database is CAplus.

Addition of two equivalent of silver(I) acetate to the diquaternary salt of 1,2,4-triazole, leads after crystallization to a one-dimensional polymer I, featuring coplanar 1,2,4-triazol-3,5-bis(ylidene) ligands coordinated to silver(I). The polymer I is insoluble in classical solvents and has been characterized by a single crystal x-ray diffraction study.

Journal of the American Chemical Society 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, Category: triazoles.

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

Guerret, Olivier published the artcile1,2,4-Triazolium-5-ylidene and 1,2,4-triazol-3,5-diylidene as new ligands for transition metals, Synthetic Route of 63598-71-0, the publication is Journal of Organometallic Chemistry (2000), 600(1-2), 112-117, database is CAplus.

Ab initio calculations (RHF-SCF-DZP and MP4) show the 4,5-dihydro-1H-1,2,4-triazolium-5-ylidene and 1,2,4-triazolidine-3,5-diylidene (4a) are true min. on the potential surface. As expected, 4a is much higher in energy than its triazole isomers (1H, 3H and 4H-1,2,4-triazoles) and the 2,3-dihydro-4H-1,2,4-triazol-3-ylidene. NaOMe adds to the triflate salts of diquaternary 1,2-dimethyl-4-alkyl-1H-1,2,4-triazoliums (9b,c; alkyl = Me, ⁱPr) to give the corresponding monocationic heterocycles, 4-alkyl-4,5-dihydro-1,2-dimethyl-5-methoxy-1H-1,2,4-triazolium triflates, in 70 and 50% yield, resp. One equivalent of Ag(I) acetate reacts with 9b leading to the bis(1,2,4-trimethyl-4,5-dihydro-1H-1,2,4-triazolium-5-ylidene)silver(I) complex (11b) in 80% yield. Under the same exptl. conditions, but using two equivalent of Ag(I) acetate, solid-state 1-dimensional polymers 12‘b,c featuring the coplanar 4-alkyl-1,2-dimethyl-1,2,4-triazolidine-3,5-diylidene ligands coordinated to Ag(I) were obtained in 90% yield. 12‘C was fully characterized including a single-crystal x-ray diffraction study.

Journal of Organometallic Chemistry 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

Khisamutdinov, G. Kh. published the artcileα-Azidopolynitroalkanes. Synthesis and vibrational spectra, Name: 5-Nitro-1H-1,2,3-triazole, the publication is Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya) (1997), 46(2), 324-327, database is CAplus.

Methods for the preparation of α-azidopolynitroalkanes by reactions of polynitroalkanes or α-(difluoroamino)polynitroalkanes with NaN₃ were developed. In the case of C(NO₂)₄, 1 or 2 nitro groups can be substituted, depending on the reaction conditions. Reaction of MeC(NO₂)₃ with NaN₃ affords nitro-1,2,3-triazole, together with MeC(NO₂)₂N₃. The IR spectra of α-azidopolynitroalkanes were studied.

Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya) 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, Name: 5-Nitro-1H-1,2,3-triazole.

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