Day: October 12, 2022

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

Vasil’eva, V. F.; Yashunskii, V. G. published the artcile< Sydnones and sydnonimines. XIII. Reaction of 3-methyl- and 3-ethylsydnones with methyl acrylate>, HPLC of Formula: 17827-61-1, the main research area is .

Treatment of N-methylglycine with NaNO2 in aqueous HCl at 0°, followed by keeping the crude N-nitroso derivative with Ac2O 10 days at room temperature, gave 56.2% 3-methylsydnone (I), b0.7 162-5°. Similarly was prepared N-nitroso-N-ethylglycine, m. 85-6°, which with Ac2O gave 45.5% 3-ethylsydnone (II), b0.5 153-6°. Heating I with CH2:CHCO2Me 36 hrs. at 125-50° gave 56.5% Me 1-methyl-δ2-pyrazoline-3-carboxylate (III), b7 103-4°, d20 1.1162, n20D 1.5093, λ 306 mμ, and 24% crude Me x-carbomethoxy-1-methylpyrazoline-propionate (IV) (positions of attached groups not certain), b0.6 138-41°. The former in 2 days in MeOH-NH8 gave 1-methyl-δ2-pyrazolinecarboxamide, m. 116-18°, λ 296 mμ, while the latter ester gave the corresponding diamide, decomposed 241-2°. III and Pb(OAc)4 in AcOH (exothermic) gave 65% Me 1-methyl-pyrazole-3-carboxylate, b1 108-10°, which with MeOH-NH3 gave the corresponding amide, m. 139-40.5°, λ 220 mμ. 1-Methylpyrazole-4-carboxylic acid refluxed with MeOH-H2SO4 in C5H6 gave the Me ester, m. 63-4.5°, which with MeOH-NH3 1 day in a sealed tube gave the amide, m. 181.5-83°. II and CH2:CHCO2Me in 34 hrs. at 125° gave 51% Me 1-ethyl-δ2-pyrazoline-3-carboxylate (V), b7 110-12° b0.8 90° 1.0860, 1.5065, and some 25% crude 1-ethyl analog of IV, b0.5 135-42°. The former in MeOH-NH3 gave the amide, m. 92-4° while the latter ester similarly gave the diamide, decomposed 251-2°. V and Pb(OAc)4, as above, gave 62.5% Me 1-ethylpyrazole-3-carboxylate, b6 115-16°, which gave the amide, m. 100-1°. Infrared and ultraviolet spectra of the esters are reported.

Zhurnal Obshchei Khimii published new progress about IR spectra. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, HPLC of Formula: 17827-61-1.

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