Category: 1046832-21-6

Bellenie, Benjamin R.; Hall, Edward; Bruce, Ian; Spendiff, Matthew; Culshaw, Andrew; McDonald, Sarah; Ambarkhane, Ameet; Chinn, Colin; Thomas, Matthew; Rosner, Elisabeth; Bracher, Marguerite; Nicklin, Paul; Marshall, Stephen; Coote, Julie; Cullen, Eva; Tessier, Clemence; Wuersch, Kuno; Lal, Ajay; Wallis, Gillian; Hollingworth, Gregory J.; Neef, James published the artcile< Discovery and Toxicological Profiling of Aminopyridines as Orally Bioavailable Selective Inhibitors of PI3-Kinase γ>, Quality Control of 1046832-21-6, the main research area is pharmacokinetic aminopyridine oral inhibitor PI3K gamma airway inflammation toxicol.

Using a novel physiol. relevant in vitro human whole blood neutrophil shape change assay, an aminopyrazine series of selective PI3Kγ inhibitors was identified and prioritized for further optimization. Severe solubility limitations associated with the series leading to low oral bioavailability and poor exposures, especially at higher doses, were overcome by moving to an aminopyridine core. Compound 33, with the optimal balance of on-target activity, selectivity, and pharmacokinetic parameters, progressed into in vivo studies and demonstrated good efficacy (10 mg/kg) in a rat model of airway inflammation. Sufficient exposures were achieved at high doses to support toxicol. studies, where unexpected inflammatory cell infiltrates in cardiovascular tissue prevented further compound development.

Journal of Medicinal Chemistry published new progress about Aminopyridines Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Quality Control of 1046832-21-6.

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

Lucas, Simon C. C.; Moore, Jane E.; Donald, Craig S.; Hawkins, Janet L. published the artcile< Synthesis of 4-Arylthieno[2,3-b]pyridines and 4-Aminothieno[2,3-b]pyridines via a Regioselective Bromination of Thieno[2,3-b]pyridine>, HPLC of Formula: 1046832-21-6, the main research area is thienopyridine oxidation regioselective bromination; bromothienopyridine regioselective preparation Suzuki Miyaura Buchwald cross coupling; aryl thienopyridine preparation; amino thienopyridine preparation.

The first regioselective, mild bromination of thieno[2,3-b]pyridine is described herein. The reaction proceeds with selectivity toward the 4-position (87% isolated yield). Subsequent cross-coupling reactions proceed in excellent yields and demonstrate the potential of 4-bromothieno[2,3-b]pyridine as a building block for use in drug discovery research.

Journal of Organic Chemistry published new progress about Boronic acids, esters Role: RCT (Reactant), RACT (Reactant or Reagent). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, HPLC of Formula: 1046832-21-6.

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

Stockmann, Henning; Todorovic, Viktor; Richardson, Paul L.; Marin, Violeta; Scott, Victoria; Gerstein, Clare; Lake, Marc; Wang, Leyu; Sadhukhan, Ramkrishna; Vasudevan, Anil published the artcile< Cell-Surface Receptor-Ligand Interaction Analysis with Homogeneous Time-Resolved FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI-Anchored Receptors>, Safety of 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is cell surface receptor ligand interaction FRET glycan engineering; transmembrane GPI anchored receptor FRET glycan engineering.

Ligand-binding assays are the linchpin of drug discovery and medicinal chem. Cell-surface receptors and their ligands have traditionally been characterized by radioligand-binding assays, which have low temporal and spatial resolution and entail safety risks. Here, the authors report a powerful alternative (GlycoFRET), where terbium-labeled fluorescent reporters are irreversibly attached to receptors by metabolic glycan engineering. For the first time, the authors show time-resolved fluorescence resonance energy transfer between receptor glycans and fluorescently labeled ligands. The authors describe GlycoFRET for a GPI-anchored receptor, a G-protein-coupled receptor, and a heterodimeric cytokine receptor in living cells with excellent sensitivity and high signal-to-background ratios. In contrast to previously described methods, GlycoFRET does not require genetic engineering or antibodies to label receptors. Given that all cell-surface receptors are glycosylated, the authors expect that GlycoFRET can be generalized with applications in chem. biol. and biotechnol., such as target engagement, receptor pharmacol., and high-throughput screening.

Journal of the American Chemical Society published new progress about Cell membrane. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Safety of 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

Klug, Dana M.; Mavrogiannaki, Eftychia M.; Forbes, Katherine C.; Silva, Lisseth; Diaz-Gonzalez, Rosario; Perez-Moreno, Guiomar; Ceballos-Perez, Gloria; Garcia-Hernandez, Raquel; Bosch-Navarrete, Cristina; Cordon-Obras, Carlos; Gomez-Linan, Claudia; Saura, Andreu; Momper, Jeremiah D.; Martinez-Martinez, Maria Santos; Manzano, Pilar; Syed, Ali; El-Sakkary, Nelly; Caffrey, Conor R.; Gamarro, Francisco; Ruiz-Perez, Luis Miguel; Gonzalez Pacanowska, Dolores; Ferrins, Lori; Navarro, Miguel; Pollastri, Michael P. published the artcile< Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis>, Product Details of C11H19BN2O2, the main research area is human African trypanosomiasis Trypanosoma brucei inhibitor BBB antitrypanosomal pharmacokinetic.

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclin. investigation of 29d (I), a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.

Journal of Medicinal Chemistry published new progress about Blood-brain barrier. 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

Johnson, Ted W.; Richardson, Paul F.; Bailey, Simon; Brooun, Alexei; Burke, Benjamin J.; Collins, Michael R.; Cui, J. Jean; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Huang, Qinhua; Kania, Robert S.; Kath, John C.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Lingardo, Laura; Liu, Wei; McTigue, Michele; Palmer, Cynthia L.; Sach, Neal W.; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published the artcile< Discovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations>, Reference of 1046832-21-6, the main research area is PF06463922 preparation macrocyclic ALK inhibitor antitumor.

Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-pos. non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and phys.-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clin. reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Reference of 1046832-21-6.

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

Bagal, Sharan K.; Gregson, Clare; O Donovan, Daniel H.; Pike, Kurt G.; Bloecher, Andrew; Barton, Peter; Borodovsky, Alexandra; Code, Erin; Fillery, Shaun M.; Hsu, Jessie Hao-Ru; Kawatkar, Sameer P.; Li, Chengzhi; Longmire, David; Nai, Youfeng; Nash, Samuel C.; Pike, Andrew; Robinson, James; Read, Jon A.; Rawlins, Phillip B.; Shen, Minhui; Tang, Jia; Wang, Peng; Woods, Haley; Williamson, Beth published the artcile< Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase>, Safety of 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is heterocyclic nitrogen analog preparation antitumor SAR enzyme inhibitor.

In this paper the discovery of potent and orally bioavailable EED ligands with good solubilities was disclosed. The solubility of the EED ligands was optimized through a variety of design tactics, with the resulting compounds exhibiting in vivo efficacy in EZH2-driven tumors.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Safety of 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

Poslusney, Michael S.; Melancon, Bruce J.; Gentry, Patrick R.; Sheffler, Douglas J.; Bridges, Thomas M.; Utley, Thomas J.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R. published the artcile< Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: The continued optimization of an MLPCN probe molecule>, Related Products of 1046832-21-6, the main research area is spirocycle preparation SAR human rat muscarinic M1 receptor selectivity; pos allosteric modulator SAR spirocycle MLPCN probe mol.

This Letter describes the further optimization of an MLPCN probe mol. (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M1 PAMs, are presented. These novel spirocycles, e.g. I, possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype.

Bioorganic & Medicinal Chemistry Letters published new progress about Homo sapiens. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Related Products of 1046832-21-6.

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