Month: October 2022

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

St. Denis, Jeffrey D.; Chessari, Gianni; Cleasby, Anne; Cons, Benjamin D.; Cowan, Suzanna; Dalton, Samuel E.; East, Charlotte; Murray, Christopher W.; OReilly, Marc; Peakman, Torren; Rapti, Magdalini; Stow, Jessie L. published the artcile< X-ray Screening of an Electrophilic Fragment Library and Application toward the Development of a Novel ERK 1/2 Covalent Inhibitor>, Product Details of C10H17BN2O2, the main research area is fragment based drug discover electrophilic fragment screening ERK2 ATP.

Fragment-based drug discovery (FBDD) has become an established method for the identification of efficient starting points for drug discovery programs. In recent years, electrophilic fragment screening has garnered increased attention from both academia and industry to identify novel covalent hits for tool compound or drug development against challenging drug targets. Herein, we describe the design and characterization of an acrylamide-focused electrophilic fragment library and screening campaign against extracellular signal-regulated kinase 2 (ERK2) using high-throughput protein crystallog. as the primary hit-finding technol. Several fragments were found to have covalently modified the ATP (ATP) binding pocket Cys166 residue. From these hits, 22 (I), a covalent ATP-competitive inhibitor with improved potency (ERK2 IC50 = 7.8 μM), was developed.

Journal of Medicinal Chemistry published new progress about Covalent inhibitors. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Product Details of C10H17BN2O2.

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

Hao, Zesheng; Wang, Weibo; Yu, Bin; Qi, Xin; Lv, You; Liu, Xiaoyu; Chen, Haoyin; Kalinina, Tatiana A.; Glukhareva, Tatiana V.; Fan, Zhijin published the artcile< Design, Synthesis, and Evaluation of Fungicidal Activity of Novel Pyrazole-Containing Strobilurin Derivatives>, Product Details of C11H19BN2O2, the main research area is pyrazole strobilurin preparation antifungal activity mol docking.

In searching for novel fungicidal leads, a series of pyrazole-containing strobilurins I (X = N, CH, R = OMe, methylamino, ethylamino, cyclopropylamino, R1 = Me, CHF2) and II were rationally designed, synthesized and characterized. Bioassays indicated that compound I (X = N, R = OMe, R1 = CHF2) (III) displayed excellent fungicidal activity against a broad spectrum of plant pathogens such as Gibberella zeae, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Phytophthora infestans, Physalospora piricola and Pellicularia sasakii with EC50 of 0.16, 0.02, 0.72, 0.07, 0.77, and 0.65μg/mL, resp., which were 3-10 times more potent than the pos. control azoxystrobin against the corresponding pathogens. Moreover, like azoxystrobin and kresoxim-Me, III displayed excellent protective activity against P. sorghi. Mol. docking validated that III and azoxystrobin would share a similar binding mode with cytochrome bc1 complex. This study demonstrates that III is a promising fungicidal candidate for further development.

Chinese Journal of Chemistry published new progress about Acetamides Role: AGR (Agricultural Use), RCT (Reactant), SPN (Synthetic Preparation), BIOL (Biological Study), USES (Uses), RACT (Reactant or Reagent), PREP (Preparation). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Product Details of C11H19BN2O2.

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

Fang, Xingang; Yin, Yan; Chen, Yen Ting; Yao, Lei; Wang, Bo; Cameron, Michael D.; Lin, Li; Khan, Susan; Ruiz, Claudia; Schroter, Thomas; Grant, Wayne; Weiser, Amiee; Pocas, Jennifer; Pachori, Alok; Schurer, Stephan; Lo Grasso, Philip; Feng, Yangbo published the artcile< Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors>, Application of C10H17BN2O2, the main research area is tetrahydroisoquinoline derivative rho kinase inhibitor antiglaucoma.

Rho kinase (ROCK) is a promising drug target for the treatment of many diseases including hypertension, multiple sclerosis, cancer, and glaucoma. The structure-activity relationships (SAR) around a series of tetrahydroisoquinolines were evaluated utilizing biochem. and cell-based assays to measure ROCK inhibition. These novel ROCK inhibitors possess high potency, high selectivity, and appropriate pharmacokinetic properties for glaucoma applications. The lead compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as excellent cell-based potency (IC50 = 51 nM). In a kinase panel profiling, 35 had an off-target hit rate of only 1.6% against 442 kinases. Pharmacol. studies showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in rats with reasonably long duration of action. These results suggest that compound 35 may serve as a promising agent for further development in the treatment of glaucoma.

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

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

Rai, Ganesha; Brimacombe, Kyle R.; Mott, Bryan T.; Urban, Daniel J.; Hu, Xin; Yang, Shyh-Ming; Lee, Tobie D.; Cheff, Dorian M.; Kouznetsova, Jennifer; Benavides, Gloria A.; Pohida, Katie; Kuenstner, Eric J.; Luci, Diane K.; Lukacs, Christine M.; Davies, Douglas R.; Dranow, David M.; Zhu, Hu; Sulikowski, Gary; Moore, William J.; Stott, Gordon M.; Flint, Andrew J.; Hall, Matthew D.; Darley-Usmar, Victor M.; Neckers, Leonard M.; Dang, Chi V.; Waterson, Alex G.; Simeonov, Anton; Jadhav, Ajit; Maloney, David J. published the artcile< Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH)>, Category: pyrazoles-derivatives, the main research area is pyrazole preparation lactate dehydrogenase inhibitor.

The authors report the discovery and medicinal chem. optimization of a novel series of pyrazole-based inhibitors of human lactate dehydrogenase (LDH). Utilization of a quant. high-throughput screening paradigm facilitated hit identification, while structure-based design and multiparameter optimization enabled the development of compounds with potent enzymic and cell-based inhibition of LDH enzymic activity. Lead compounds such as 63 exhibit low nM inhibition of both LDHA and LDHB, submicromolar inhibition of lactate production, and inhibition of glycolysis in MiaPaCa2 pancreatic cancer and A673 sarcoma cells. Moreover, robust target engagement of LDHA by lead compounds was demonstrated using the cellular thermal shift assay (CETSA), and drug-target residence time was determined via SPR. Anal. of these data suggests that drug-target residence time (off-rate) may be an important attribute to consider for obtaining potent cell-based inhibition of this cancer metabolism target.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Category: pyrazoles-derivatives.

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