Category: 1046832-21-6

Westaway, Susan M.; Preston, Alex G. S.; Barker, Michael D.; Brown, Fiona; Brown, Jack A.; Campbell, Matthew; Chung, Chun-wa; Drewes, Gerard; Eagle, Robert; Garton, Neil; Gordon, Laurie; Haslam, Carl; Hayhow, Thomas G.; Humphreys, Philip G.; Joberty, Gerard; Katso, Roy; Kruidenier, Laurens; Leveridge, Melanie; Pemberton, Michelle; Rioja, Inma; Seal, Gail A.; Shipley, Tracy; Singh, Onkar; Suckling, Colin J.; Taylor, Joanna; Thomas, Pamela; Wilson, David M.; Lee, Kevin; Prinjha, Rab K. published the artcile< Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives>, Related Products of 1046832-21-6, the main research area is pyrido pyrimidinone derivative preparation histone lysine demethylase KDM4 inhibitor.

Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochem. and target-specific, cellular mechanistic assays.

Journal of Medicinal Chemistry published new progress about Histone lysine demethylase inhibitors. 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

Mammoliti, Oscar; Palisse, Adeline; Joannesse, Caroline; El Bkassiny, Sandy; Allart, Brigitte; Jaunet, Alex; Menet, Christel; Coornaert, Beatrice; Sonck, Kathleen; Duys, Inge; Clement-Lacroix, Philippe; Oste, Line; Borgonovi, Monica; Wakselman, Emanuelle; Christophe, Thierry; Houvenaghel, Nicolas; Jans, Mia; Heckmann, Bertrand; Saniere, Laurent; Brys, Reginald published the artcile< Discovery of the S1P2 Antagonist GLPG2938 (1-[2-Ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a Preclinical Candidate for the Treatment of Idiopathic Pulmonary Fibrosis>, Related Products of 1046832-21-6, the main research area is S1PR2 antagonist idiopathic pulmonary fibrosis GLPG2938.

Mounting evidence from the literature suggests that blocking S1P2 receptor (S1PR2) signaling could be effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, only a few antagonists have been so far disclosed. A chem. enablement strategy led to the discovery of a pyridine series with good antagonist activity. A pyridazine series with improved lipophilic efficiency and with no CYP inhibition liability was identified by scaffold hopping. Further optimization led to the discovery of 40 (GLPG2938)(I), a compound with exquisite potency on a phenotypic IL8 release assay, good pharmacokinetics, and good activity in a bleomycin-induced model of pulmonary fibrosis.

Journal of Medicinal Chemistry published new progress about Drug design. 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

Pascanu, Vlad; Hansen, Peter R.; Bermejo Gomez, Antonio; Ayats, Carles; Platero-Prats, Ana E.; Johansson, Magnus J.; Pericas, Miquel A.; Martin-Matute, Belen published the artcile< Highly Functionalized Biaryls via Suzuki-Miyaura Cross-Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes>, COA of Formula: C11H19BN2O2, the main research area is biaryl preparation green chem; arylboronic acid aryl halide Suzuki Miyaura flow chem microwave; palladium nanoparticle metal organic framework catalyst; MOF catalysis; flow chemistry; heterocycles; suzuki-miyaura.

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt % Pd@MIL-101(Cr)-NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted mols. are important intermediates in the synthesis of pharmaceuticals and the versatility of this catalytic system is exemplified, which affords better yields than currently existing com. procedures. Most importantly, Pd@MIL-101-NH2 was packed in a micro-flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chem. for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large-scale applications.

ChemSusChem published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, COA of Formula: C11H19BN2O2.

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

Ran, Kai; Zeng, Jun; Wan, Guoquan; He, Xiaojie; Feng, Zhanzhan; Xiang, Wang; Wei, Wei; Hu, Xiang; Wang, Ningyu; Liu, Zhihao; Yu, Luoting published the artcile< Design, synthesis and biological evaluations of a series of Pyrido[1,2-a]pyrimidinone derivatives as novel selective FGFR inhibitors>, Application of C11H19BN2O2, the main research area is pyridopyrimidinone preparation antitumor activity FGFR inhibitor; FGFR; Solubility; Tumor growth inhibition; pyrido[1,2-a]pyrimidinone.

Herein, the design and synthesis of pyrido[1,2-a]pyrimidinone derivatives I (R1 = methoxyethoxy, tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl, 1H-pyrazol-4-yl, etc.) and II (R2 = Me, azetidin-3-yl, etc.; R3 = 3-[(propan-2-yl)amino]propyl, prop-2-yn-1-yl, cyclopropylmethyl, etc.) as potent FGFR inhibitors were described. Examination of structure-activity relationships and preliminary assessment identified I (R1 = 1-methyl-1H-pyrazol-4-yl) as a novel FGFR inhibitor that displayed excellent potency in vitro. Candidate I [R1 = 1-methyl-1H-pyrazol-4-yl (III)] suppressed the phosphorylation of FGFR signaling pathways and induced cell cycle arrest and apoptosis at low nanomolar concentration In the kinase inhibition profile, III showed excellent kinase selectivity for the FGFR family. Furthermore, III showed higher aqueous solubility than Erdafitinib. Moreover, III exhibited potent antitumor activity (tumor growth inhibition = 106.4%) in FGFR2-amplified SNU-16 gastric cancer xenograft model using a daily oral dose of 30 mg/kg. These results suggest that III is a promising candidate for further drug development.

European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Application of C11H19BN2O2.

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

Klug, Dana M.; Diaz-Gonzalez, Rosario; DeLano, Travis J.; Mavrogiannaki, Eftychia M.; Buskes, Melissa J.; Dalton, Raeann M.; Fisher, John K.; Schneider, Katherine M.; Hilborne, Vivian; Fritsche, Melanie G.; Simpson, Quillon J.; Tear, Westley F.; Devine, William G.; Perez-Moreno, Guiomar; Ceballos-Perez, Gloria; Garcia-Hernandez, Raquel; Bosch-Navarrete, Cristina; Ruiz-Perez, Luis Miguel; Gamarro, Francisco; Gonzalez-Pacanowska, Dolores; Martinez-Martinez, Maria Santos; Manzano-Chinchon, Pilar; Navarro, Miguel; Pollastri, Michael P.; Ferrins, Lori published the artcile< Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity>, Application In Synthesis of 1046832-21-6, the main research area is imidazoquinoline chemotype antitrypanosomal activity structure activity relationship.

Human African trypanosomiasis is a neglected tropical disease (NTD) that is fatal if left untreated. Although approx. 13 million people live in moderate- to high-risk areas for infection, current treatments are plagued by problems with safety, efficacy, and emerging resistance. In an effort to fill the drug development pipeline for HAT, we have expanded previous work exploring the chemotype represented by the compound NEU-1090, with a particular focus on improvement of absorption, distribution, metabolism and elimination (ADME) properties. These efforts resulted in several compounds with substantially improved aqueous solubility, although these modifications typically resulted in a loss of trypanosomal activity. We herein report the results of our investigation into the antiparasitic activity, toxicity, and ADME properties of this class of compounds in the interest of informing the NTD drug discovery community and avoiding duplication of effort.

RSC Medicinal Chemistry published new progress about Blood. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Application In Synthesis of 1046832-21-6.

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

Beveridge, Ramsay E.; Wallweber, Heidi Ackerly; Ashkenazi, Avi; Beresini, Maureen; Clark, Kevin R.; Gibbons, Paul; Ghiro, Elise; Kaufman, Susan; Larivee, Alexandre; Leblanc, Melissa; Leclerc, Jean-Philippe; Lemire, Alexandre; Ly, Cuong; Rudolph, Joachim; Schwarz, Jacob B.; Srivastava, Sanjay; Wang, Weiru; Zhao, Liang; Braun, Marie-Gabrielle published the artcile< Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1α Inhibitory Activity>, Application In Synthesis of 1046832-21-6, the main research area is preparation BRaf amino thieno pyrimidine derivative IRE1 inhibitor cancer.

Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallog. and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle anal. revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogs such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Application In Synthesis of 1046832-21-6.

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

Saal, Christoph; Becker, Axel; Krier, Mireille; Fuchss, Thomas published the artcile< Atropisomerism - A Neglected Way to Escape Out of Solubility Flatlands>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is atropisomer aqueous solubility enantiomers; ATM; ATM-inhibitor; Ataxia-telangiectasia mutated kinase; Atropisomerism; Chirality; Crystal structure; Dissolution; Kinase inhibitor; M4076; Solubility.

Low solubility of drugs represents a major challenge during research and development. Ways to overcome this are either focused on formulation development or optimization of the mol. structure of the drug. The latter is not only governed by the constitution of the mol. but also by its stereochem. Development of enantiomers in contrast to racemic mixtures has become the state of the art over the last decades as this leads to higher potency and selectivity. Thus, enantiopure drugs require lower doses compared to their racemates. Addnl., selecting one enantiomer also leads to improved solubility of the drug compared to its racemic compound While this effect is well known for enantiomers and racemic compounds where chirality is introduced via a chiral central atom, here we describe the first case where improved solubility is realized by selecting an axially chiral atropisomer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Atropisomers. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Name: 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

Drew, Samuel L.; Thomas-Tran, Rhiannon; Beatty, Joel W.; Fournier, Jeremy; Lawson, Kenneth V.; Miles, Dillon H.; Mata, Guillaume; Sharif, Ehesan U.; Yan, Xuelei; Mailyan, Artur K.; Ginn, Elaine; Chen, Jie; Wong, Kent; Soni, Divyank; Dhanota, Puja; Chen, Pei-Yu; Shaqfeh, Stefan G.; Meleza, Cesar; Pham, Amber T.; Chen, Ada; Zhao, Xiaoning; Banuelos, Jesus; Jin, Lixia; Schindler, Ulrike; Walters, Matthew J.; Young, Stephen W.; Walker, Nigel P.; Leleti, Manmohan Reddy; Powers, Jay P.; Jeffrey, Jenna L. published the artcile< Discovery of Potent and Selective PI3Kγ Inhibitors>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is PI3K gamma inhibitors ATP binding site SAR hydrogen bond.

The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homol. across the class I PI3K isoforms. Here, we describe the design of a novel series of potent PI3Kγ inhibitors that attain high isoform selectivity through the divergent projection of substituents into both the “”selectivity”” and “”alkyl-induced”” pockets within the ATP (ATP) binding site of PI3Kγ. These efforts have culminated in the discovery of 5-[2-amino-3-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-2-[(1S)-1-cyclopropylethyl]-7-(trifluoromethyl)-2,3-dihydro-1H-isoindol-1-one (4(I), IC50 = 0.064 μM, THP-1 cells), which displays >600-fold selectivity for PI3Kγ over the other class I isoforms and is a promising step toward the identification of a clin. development candidate. The structure-activity relationships identified throughout this campaign demonstrate that greater γ-selectivity can be achieved by inhibitors that occupy an “”alkyl-induced”” pocket and possess bicyclic hinge-binding motifs capable of forming more than one hydrogen bond to the hinge region of PI3Kγ.

Journal of Medicinal Chemistry published new progress about Crystal structure (compound 4 bound to hPI3Kγ). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Name: 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

He, Shuwen; Li, Peng; Dai, Xing; McComas, Casey C.; Du, Chunyan; Wang, Ping; Lai, Zhong; Liu, Hong; Yin, Jingjun; Bulger, Paul G.; Dang, Qun; Xiao, Dong; Zorn, Nicolas; Peng, Xuanjia; Nargund, Ravi P.; Palani, Anandan published the artcile< Facile functionalization at the C2 position of a highly substituted benzofuran>, Recommanded Product: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is iodobenzofuran preparation Suzuki coupling; benzofuran preparation.

To expedite an SAR study on C(2) of a highly substituted benzofuran ring system, a method for the preparation of a key precursor, iodide I, was developed. From I, a diverse set of compounds with different substituents at C(2) were prepared efficiently by Suzuki reaction.

Tetrahedron Letters published new progress about Benzofurans Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Recommanded Product: 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

Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J. Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published the artcile< Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib>, COA of Formula: C11H19BN2O2, the main research area is crizotinib resistant lymphoma kinase mutation inhibitor preparation SAR.

Crizotinib, an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS pos. patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine (I), which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclin. pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

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

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