pyrazoles-derivatives

Liang, Jun published the artcileLead Optimization of a 4-Aminopyridine Benzamide Scaffold To Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors, Synthetic Route of 763120-58-7, the publication is Journal of Medicinal Chemistry (2013), 56(11), 4521-4536, database is CAplus and MEDLINE.

Herein the authors report the authors’ lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead mol. 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide. The authors used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide. Further optimization eventually led to 2-Chloro-4-cyano-6-fluoro-N-(2-((1R,2R)-2-fluorocyclopropanecarboxamido)pyridin-4-yl)benzamide that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, 2-Chloro-4-cyano-6-fluoro-N-(2-((1R,2R)-2-ffluorocyclopropanecarboxamido)pyridin-4-yl)benzamide showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Synthetic Route of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Popov, Mark S. published the artcileGas Chromatography-Mass Spectrometry Quantification of 1,1-Dimethylhydrazine Transformation Products in Aqueous Solutions: Accelerated Water Sample Preparation, HPLC of Formula: 930-36-9, the publication is Molecules (2021), 26(19), 5743, database is CAplus and MEDLINE.

The use of highly toxic rocket fuel based on 1,1-dimethylhydrazine (UDMH) in many types of carrier rockets poses a threat to environment and human health associated with an ingress of UDMH into wastewater and natural reservoirs and its transformation with the formation of numerous toxic nitrogen-containing products. Their GC-MS quantification in aqueous samples requires matrix change and is challenging due to high polarity of analytes. To overcome this problem, accelerated water sample preparation (AWASP) based on the complete removal of water with anhydrous sodium sulfate and transferring analytes into dichloromethane was used. Twenty-nine UDMH transformation products including both the acyclic and heterocyclic compounds of various classes were chosen as target analytes. AWASP ensured attaining near quant. extraction of 23 compounds with sample preparation procedure duration of no more than 5 min. Combination of AWASP with gas chromatog.-mass spectrometry and using pyridine-d5 as an internal standard allowed for developing the rapid, simple, and low-cost method for simultaneous quantification of UDMH transformation products with detection limits of 1-5 μg L^-1 and linear concentration range covering 4 orders of magnitude. The method has been validated and successfully tested in the anal. of aqueous solutions of rocket fuel subjected to oxidation with atm. oxygen, as well as pyrolytic gasification in supercritical water modeling wastewater from carrier rockets launch sites.

Molecules published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, HPLC of Formula: 930-36-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Lemurell, Malin published the artcileNovel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease, HPLC of Formula: 724710-02-5, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4325-4349, database is CAplus and MEDLINE.

5-Lipoxygenase (5-LO)-activating protein (FLAP) inhibitors have proven to attenuate 5-LO pathway activity and leukotriene production in human clin. trials. However, previous clin. candidates have been discontinued and the link between FLAP inhibition and outcome in inflammatory diseases remains to be established. We here describe a novel series of FLAP inhibitors identified from a screen of 10k compounds and the medicinal chem. strategies undertaken to progress this series. Compound I showed good overall properties and a pIC₅₀ hWB_free of 8.1 and an lipophilic ligand efficiency of 5.2. Target engagement for I was established in dogs using ex vivo measurement of leukotriene B₄ (LTB₄) levels in blood with good correlation to in vitro potency. A predicted human dose of 280 mg b.i.d. suggests a wide margin to any identified in vitro off-target effects and sufficient exposure to achieve an 80% reduction of LTB₄ levels in humans. Compound I is progressed to preclin. in vivo safety studies.

Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, HPLC of Formula: 724710-02-5.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Asegbeloyin, Jonnie N. published the artcileSynthesis, characterization, and biological activity of N’-[(Z)-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide and its Co(II), Ni(II), and Cu(II) complexes, Recommanded Product: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Bioinorganic Chemistry and Applications (2014), 718175/1-718175/11, 12 pp., database is CAplus and MEDLINE.

Reaction of 1-phenyl-3-methyl-4-benzoyl-pyrazol-5-one and benzoyl hydrazide in refluxing EtOH gave N’-[(Z)-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide (HL1), which was characterized by NMR spectroscopy and single-crystal x-ray structure study. X-ray diffraction analyses of the crystals revealed a nonplanar mol., existing in the keto-amine form, with intermol. H bonding forming a seven-membered ring system. The reaction of HL1 with Co(II), Ni(II), and Cu(II) halides gave the corresponding complexes, which were characterized by elemental anal., molar conductance, magnetic measurements, and IR and electronic spectral studies. The compounds were screened for their in vitro cytotoxic activity against HL-60 human promyelocytic leukemia cells and antimicrobial activity against some bacteria and yeasts. The compounds are potent against HL-60 cells with the IC50 value â‰? μM, while some of the compounds were active against few studied Gram-pos. bacteria.

Bioinorganic Chemistry and Applications published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C17H14N2O2, Recommanded Product: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Hara, Naofumi published the artcileC2-Selective silylation of pyridines by a rhodium-aluminum complex, Product Details of C4H6N2, the publication is Chemical Communications (Cambridge, United Kingdom) (2021), 57(48), 5957-5960, database is CAplus and MEDLINE.

We have developed a C2-selective dehydrogenative mono-silylation of a variety of pyridines using a Rh-Al complex [(R₂PCH₂N-1,2-C₆H₄NMe-1,2-C₆H₄NCH₂PR₂)AlClRhCl(L)]_n (R = Ph, ⁱPr; n = 1, L = nbd; n = 2, L void). Both the site- and mono-selectivity are controlled via the pyridine coordination to the Lewis-acidic Al center prior to the activation of the pyridine C(2)-H bond at the proximal Rh center. A reaction mechanism is proposed based on several mechanistic studies, including the isolation of a (2-pyridyl)silylrhodium intermediate.

Chemical Communications (Cambridge, United Kingdom) published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Product Details of C4H6N2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Tao published the artcileDiscovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir, Product Details of C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2018), 61(14), 6308-6327, database is CAplus and MEDLINE.

The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp²-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclin. species. However, the phys. properties of 3 limited plasma exposure at higher doses, both in preclin. studies and in clin. trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clin. trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.

Journal of Medicinal Chemistry published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H7NO2, Product Details of C3H5BN2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Lu, Jinzhen published the artcileOctapi Interactions: Self-Assembly of a Pd-Based [2]Catenane Driven by Eightfold π Interactions, Related Products of pyrazoles-derivatives, the publication is Journal of the American Chemical Society (2009), 131(30), 10372-10373, database is CAplus and MEDLINE.

An unprecedented 2.5 nm array of π interactions between eight aromatic rings drives the formation of a [2]catenane, {[Pd(dppp)]₂L²}₂⁸⁺ (L = 1,2-bis(4-(4-pyridyl)pyrazolyl)ethane; dppp = 1,3-bis(diphenylphosphino)propane). Disruption of this array through the use of longer ligands gave only single, uncatenated rings as observed in {[Pd(dppp)₂]₂L¹}⁴⁺ (L = 1,3-bis(4-(4-pyridyl)pyrazolyl)propane). The catenated complex persists in solution alongside its constituent metallomacrocycles.

Journal of the American Chemical Society published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Related Products of pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Lu, Jinzhen published the artcileHeteroligand Molecular “Stirrups” Using Conformationally Flexible Ditopic Pyridyl-Pyrazolyl Ligands, Category: pyrazoles-derivatives, the publication is Inorganic Chemistry (2009), 48(16), 7525-7527, database is CAplus and MEDLINE.

Heteroligand mol. stirrups form by the self-assembly of flexible ditopic ligands in combination with 4,4′-bipyridine and [(dppp)Pd]²⁺ [dppp = 1,3-bis(diphenylphosphino)propane]. Crystallog. anal. shows that the ligands, bis[3-(4-pyridyl)pyrazolyl]-m-xylene (mXy^4py3pz) and bis[4-(4-pyridyl)pyrazolyl]-p-xylene (pXy^4py4pz) form [{(dppp)Pd}₂(4,4′-bipy)(L)](OTf)₄ (1·4OTf and 2·4OTf, resp.) in the solid state, with remarkably similar structures considering the differences in substitution patterns between the two ligands. The self-assembly of both 1⁴⁺ and 2⁴⁺ is assisted by face-to-face π interactions on the exterior of the macrocycle between the Ph rings of the dppp ligands and the pyridyl groups of the ditopic ligands.

Inorganic Chemistry published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Category: pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Tarr, James C. published the artcileTargeting Selective Activation of M₁ for the Treatment of Alzheimer’s Disease: Further Chemical Optimization and Pharmacological Characterization of the M₁ Positive Allosteric Modulator ML169, Computed Properties of 763120-58-7, the publication is ACS Chemical Neuroscience (2012), 3(11), 884-895, database is CAplus and MEDLINE.

The M₁ muscarinic acetylcholine receptor is thought to play an important role in memory and cognition, making it a potential target for the treatment of Alzheimer’s disease (AD) and schizophrenia. Moreover, M₁ interacts with BACE1 and regulates its proteasomal degradation, suggesting selective M₁ activation could afford both palliative cognitive benefit as well as disease modification in AD. A key challenge in targeting the muscarinic acetylcholine receptors is achieving mAChR subtype selectivity. Our lab has previously reported the M₁ selective pos. allosteric modulator ML169. Herein we describe our efforts to further optimize this lead compound by preparing analog libraries and probing novel scaffolds. We were able to identify several analogs that possessed submicromolar potency, with our best example displaying an EC₅₀ of 310 nM. The new compounds maintained complete selectivity for the M₁ receptor over the other subtypes (M₂-M₅), displayed improved DMPK profiles, and potentiated the carbachol (CCh)-induced excitation in striatal MSNs. Selected analogs were able to potentiate CCh-mediated non-amyloidogenic APPα release, further strengthening the concept that M₁ PAMs may afford a disease-modifying role in the treatment of AD.

ACS Chemical Neuroscience published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C9H5ClO2, Computed Properties of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Lizarzaburu, Mike published the artcileDiscovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetes mellitus, Quality Control of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(18), 5942-5947, database is CAplus and MEDLINE.

N-alkylphenylalaninamides of pyridinylphenyl- and oxobipyridinylamines such as I were prepared as GPR142 agonists for potential use as antidiabetic agents for type 2 diabetes and tested for their agonism of GPR142 in vitro and in human plasma and their inhibition of cytochrome P 450 enzymes such as isoforms 3A4 and 2D6. Optimization of the original lead compound gave agonists 90 times more potent against human GPR142. Inhibition of cytochrome P 450 isoforms 3A4 and 2D6 was reduced by increasing the polarity of the biarylamine moiety. The pharmacokinetics of I and a thiazolylmethyl phenylalaninamide of an aminopyridinylbenzoate were determined in rats.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Quality Control of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics