Day: October 12, 2022

Osawa, Akio; Kaiho, Terumitsu; Ito, Takashi; Okada, Mamiko; Kawabata, Chikako; Yamaguchi, Kentaro; Igeta, Hiroshi published the artcile< Reactions of N-aminopyrazoles with halogenating reagents and synthesis of 1,2,3-triazines>, Product Details of C9H7BrN2, the main research area is triazine; pyrazolamine reaction halogenating agent; ring expansion aminopyrazole.

Reactions of N-aminopyrazoles with halogenating reagents (Cl2, Br2, I2, BrCl, ICl, IBr, N-chlorosuccinimide, and N-bromosuccinimide) were examined Some of these reagents preferentially leas to oxidation of the amino group to give the corresponding 1,2,3-triazines as major products, while others mainly gave either or both of 1-amino-4-halopyrazoles and 5-halo-1,2,3-triazines as the result of halogenation of the 4-position of the pyrazole ring prior to the oxidation of the amino group. In some cases, the oxidation of the amino group and the halogenation of the pyrazole ring proceeded concurrently to form not only the unhalogenated triazines but also the 1-amino-4-halopyrazines and the 5-halotriazines. Various reagents and reaction conditions were explored to utilize the reaction for the synthesis of halogenated and unhalogenated 1,2,3-triazines.

Chemical & Pharmaceutical Bulletin published new progress about Halogenation. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Product Details of C9H7BrN2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Schulte, James P. II; Tweedie, Scott R. published the artcile< Palladium-catalyzed couplings of heteroaryl amines with aryl halides using sodium phenolate as the stoichiometric base>, Category: pyrazoles-derivatives, the main research area is microwave mediated palladium catalyzed coupling heteroaryl amine aryl halide; pyrazole pyridine pyrazine isoxazole arylamino preparation.

Heteroaryl amines are efficiently coupled (in two hours) to aryl halides with catalytic Pd2(dba)3 and Xantphos to provide the corresponding biaryl amines under microwave and standard thermal conditions. E.g., 3-tert-butyl-1-methyl-1H-pyrazol-5-amine reacts with p-bromobenzonitrile in the presence of 1.25 mol% Pd2(dba)3, 3 mo% Xantphos ligand and 1,5 equivalent NaOPh/dioxane under microwave conditions to give 91% yield of biarylamine I. The use of organic-soluble Na phenolate (NaOPh) as the stoichiometric base promotes facile coupling of a variety of substrates in excellent yields.

Synlett published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent) (heteroaryl). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Category: pyrazoles-derivatives.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Foces-Foces, Concepcion; Alkorta, Ibon; Elguero, Jose published the artcile< Supramolecular structure of 1H-pyrazoles in the solid state: a crystallographic and ab initio study>, Formula: C9H7BrN2, the main research area is pyrazole derivative supramol structure solid state ab initio.

The secondary structure of 1H-unsubstituted pyrazole derivatives bearing only one hydrogen-donor group and one or more acceptor groups has been analyzed in terms of some descriptors representing the substituents at C3 and C5. The substituent at C4 appears to affect mainly the tertiary or quaternary structure of these compounds The proposed semi-quant. model, which explains most hydrogen-bonded motifs as a combination of the effects of substituents at C3 and C5, has also been examined as a function of the steric and polarizability effects of these substituents represented by molar refractivity. The model also applies to other five-membered rings (1,2,4-triazoles, 1,2,4-diazaphospholes and 1,2,4-diazaarsoles). Furthermore, ab initio calculations at RHF/6-31G* have been performed to discover the relative stability of three of the four hydrogen-bond patterns displayed by several sym. pyrazoles (dimers, trimers, tetramers). The fourth motif, catemers, has only been discussed geometrically.

Acta Crystallographica, Section B: Structural Science published new progress about Density functional theory. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Formula: C9H7BrN2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Gopalsamy, Ariamala; Aulabaugh, Ann E.; Barakat, Amey; Beaumont, Kevin C.; Cabral, Shawn; Canterbury, Daniel P.; Casimiro-Garcia, Agustin; Chang, Jeanne S.; Chen, Ming Z.; Choi, Chulho; Dow, Robert L.; Fadeyi, Olugbeminiyi O.; Feng, Xidong; France, Scott P.; Howard, Roger M.; Janz, Jay M.; Jasti, Jayasankar; Jasuja, Reema; Jones, Lyn H.; King-Ahmad, Amanda; Knee, Kelly M.; Kohrt, Jeffrey T.; Limberakis, Chris; Liras, Spiros; Martinez, Carlos A.; McClure, Kim F.; Narayanan, Arjun; Narula, Jatin; Novak, Jonathan J.; O’Connell, Thomas N.; Parikh, Mihir D.; Piotrowski, David W.; Plotnikova, Olga; Robinson, Ralph P.; Sahasrabudhe, Parag V.; Sharma, Raman; Thuma, Benjamin A.; Vasa, Dipy; Wei, Liuqing; Wenzel, A. Zane; Withka, Jane M.; Xiao, Jun; Yayla, Hatice G. published the artcile< PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease>, Reference of 936250-20-3, the main research area is pf07059013 noncovalent Hb modulator sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult Hb (HbA) that results in sickled Hb (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clin. candidate PF-07059013 (23). The seminal hit mol. was discovered by virtual screening and confirmed through a series of biochem. and biophys. studies. After a significant optimization effort, we arrived at 23, a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-wk multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clin. trials.

Journal of Medicinal Chemistry published new progress about Crystal structure. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Reference of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Becica, Joseph; Hruszkewycz, Damian P.; Steves, Janelle E.; Elward, Jennifer M.; Leitch, David C.; Dobereiner, Graham E. published the artcile< High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides>, Computed Properties of 13788-92-6, the main research area is tertiary sulfonamide preparation palladium catalyst; secondary sulfonamide heteroaryl halide arylation high throughput screening.

Through targeted high-throughput experimentation (HTE), authors have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct densely functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chem. AdBippyPhos is particularly effective for the installation of heteroaromatic groups. Computational steric parametrization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.

Organic Letters published new progress about Arenesulfonamides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Computed Properties of 13788-92-6.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Large, Jonathan M.; Osborne, Simon A.; Smiljanic-Hurley, Ela; Ansell, Keith H.; Jones, Hayley M.; Taylor, Debra L.; Clough, Barbara; Green, Judith L.; Holder, Anthony A. published the artcile< Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues [Erratum to document cited in CA159:639162]>, Formula: C15H19BN2O2, the main research area is erratum imidazopyridazine inhibitor preparation antimalarial Plasmodium kinase inhibitor.

On page 6023, Table 4 was incomplete; the corrected table is given.

Bioorganic & Medicinal Chemistry Letters published new progress about Antimalarials. 1002334-12-4 belongs to class pyrazoles-derivatives, and the molecular formula is C15H19BN2O2, Formula: C15H19BN2O2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

McCann, Scott D.; Reichert, Elaine C.; Arrechea, Pedro Luis; Buchwald, Stephen L. published the artcile< Development of an Aryl Amination Catalyst with Broad Scope Guided by Consideration of Catalyst Stability>, Electric Literature of 13788-92-6, the main research area is dialkylbiaryl monosphosphine ligand preparation amination coupling catalyst.

The authors have developed a new dialkylbiaryl monophosphine ligand, GPhos, that supports a palladium catalyst capable of promoting carbon-nitrogen cross-coupling reactions between a variety of primary amines and aryl halides; in many cases, these reactions can be carried out at room temperature The reaction development was guided by the idea that the productivity of catalysts employing BrettPhos-like ligands is limited by their lack of stability at room temperature Specifically, it was hypothesized that primary amine and N-heteroaromatic substrates can displace the phosphine ligand, leading to the formation of catalytically dormant palladium complexes that reactivate only upon heating. This notion was supported by the synthesis and kinetic study of a putative off-cycle Pd complex. Consideration of this off-cycle species, together with the identification of substrate classes that are not effectively coupled at room temperature using previous catalysts, led to the design of a new dialkylbiaryl monophosphine ligand. An Ot-Bu substituent was added ortho to the dialkylphosphino group of the ligand framework to improve the stability of the most active catalyst conformer. To offset the increased size of this substituent, the authors also removed the para i-Pr group of the non-phosphorus-containing ring, which allowed the catalyst to accommodate binding of even very large α-tertiary primary amine nucleophiles. In comparison to previous catalysts, the GPhos-supported catalyst exhibits better reactivity both under ambient conditions and at elevated temperatures Its use allows for the coupling of a range of amine nucleophiles, including (1) unhindered, (2) five-membered-ring N-heterocycle-containing, and (3) α-tertiary primary amines, each of which previously required a different catalyst to achieve optimal results.

Journal of the American Chemical Society published new progress about Amination. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Electric Literature of 13788-92-6.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Jiang, Bo; Ye, Qin; Fan, Wei; Wang, Shu-Liang; Tu, Shu-Jiang; Li, Guigen published the artcile< Four-component strategy for selective synthesis of azepino[5,4,3-cd]indoles and pyrazolo[3,4-b]pyridines>, Electric Literature of 118430-74-3, the main research area is pyrazolamine arylglyoxal hydrate aniline multicomponent domino cyclocondensation; hydropyrazoloazepinoindole preparation; pyrazolopyridine preparation.

A novel four-component strategy for the selective synthesis of fused 1,5,9,10-tetrahydropyrazolo[4′,3′:6,7]azepino[5,4,3-cd]indoles and pyrazolo[3,4-b]pyridines by domino reactions of 1-substituted 5-pyrazolamines, arylglyoxal monohydrates, and anilines was established. The bond-forming efficiency, accessibility of starting materials and substrate scope provide invaluable access to tetra-, and bis-heterocyclic scaffolds.

Chemical Communications (Cambridge, United Kingdom) published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Electric Literature of 118430-74-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Liu, Dandan; Ge, Huan; Xu, Fangling; Xu, Yufang; Liu, Wenjun; Li, Honglin; Zhu, Lili; Diao, Yanyan; Zhao, Zhenjiang published the artcile< Design, synthesis and SAR study of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors>, Application In Synthesis of 936250-20-3, the main research area is aminopyridine preparation docking antitumor SAR JAK2 inhibitor human.

The abnormal activation of JAK2 kinase is closely related to the occurrence and progression of myeloproliferative neoplasms (MPNs). At present, there is still an obvious unmet medical need for selective JAK2 inhibitors in clinic. In this paper, a class of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors was obtained by combining drug design, synthesis and structure-activity relationship studies based on the previously identified lead Crizotinib. Among them, I exhibited high inhibitory activity against JAK2 with an IC50 of 9 9 nmol/L, moreover, it showed 276- and 184-fold selectivity over JAK1 and JAK3, resp. Besides, I had a significant antiproliferative activity against HEL cells, and also inhibited the phosphorylation of JAK2 and its down-stream signaling pathway. These results indicated that 2-aminopyridine compound I had the potential to be developed as a selective JAK2 inhibitor for further study.

Chinese Chemical Letters published new progress about Aminopyridines Role: PAC (Pharmacological Activity), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Application In Synthesis of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Swain, Nigel. A.; Batchelor, Dave; Beaudoin, Serge; Bechle, Bruce M.; Bradley, Paul A.; Brown, Alan D.; Brown, Bruce; Butcher, Ken J.; Butt, Richard P.; Chapman, Mark L.; Denton, Stephen; Ellis, David; Galan, Sebastien R. G.; Gaulier, Steven M.; Greener, Ben S.; de Groot, Marcel J.; Glossop, Mel S.; Gurrell, Ian K.; Hannam, Jo; Johnson, Matthew S.; Lin, Zhixin; Markworth, Christopher J.; Marron, Brian E.; Millan, David S.; Nakagawa, Shoko; Pike, Andy; Printzenhoff, David; Rawson, David J.; Ransley, Sarah J.; Reister, Steven M.; Sasaki, Kosuke; Storer, R. Ian; Stupple, Paul A.; West, Christopher W. published the artcile< Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7>, Electric Literature of 936250-20-3, the main research area is PF05089771 drug design synthesis NaV17 sodium channel inhibitor pain; diaryl ether aryl sulfonamide preparation sodium channel inhibitor pharmacokinetics.

A series of acidic diaryl ether heterocyclic sulfonamides that are potent and sub-type selective NaV1.7 inhibitors is described. Optimization of early lead matter focused on removal of structural alerts, improving metabolic stability and reducing cytochrome P 450 inhibition driven drug-drug interaction concerns to deliver the desired balance of preclin. in vitro properties. Concerns over non-metabolic routes of clearance, variable clearance in pre-clin. species and subsequent low confidence human pharmacokinetic predictions led to the decision to conduct a human microdose study to determine clin. pharmacokinetics. The design strategies and results from pre-clin. PK and clin. human microdose PK data are described leading to the discovery of the first sub-type selective NaV1.7 inhibitor clin. candidate PF-05089771 (34) which binds to a site in the voltage sensing domain.

Journal of Medicinal Chemistry published new progress about Analgesics. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Electric Literature of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics