Month: October 2022

Ding, Yun; Chai, Jing; Centrella, Paolo A.; Gondo, Chenaimwoyo; De Lorey, Jennifer L.; Clark, Matthew A. published the artcile< Development and Synthesis of DNA-Encoded Benzimidazole Library>, Computed Properties of 118430-74-3, the main research area is preparation DNA conjugated benzimidazole library NK3 receptor antagonist; DNA tagged fluoronitrobenzamide amine aldehyde; DNA-encoded library technology; benzimidazole.

Encoded library technol. (ELT) is an effective approach to the discovery of novel small-mol. ligands for biol. targets. A key factor for the success of the technol. is the chem. diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.

ACS Combinatorial Science published new progress about Chemical library. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Computed Properties of 118430-74-3.

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

Petzold, Daniel; Koenig, Burkhard published the artcile< Photocatalytic Oxidative Bromination of Electron-Rich Arenes and Heteroarenes by Anthraquinone>, Name: 4-Bromo-3-phenyl-1H-pyrazole, the main research area is arene heteroarene oxidative bromination photocatalyst sodium anthraquinonesulfonate.

The estimated excited oxidation potential of sodium anthraquinone-2-sulfonate (SAS) increases from 1.8 V to ∼2.3 V vs. SCE by protonation with Bronsted acids. This increased photooxidation power of protonated anthraquinone was used for the regio-selective oxidative bromination of electron rich (hetero)arenes and drugs in good yield. The mild reaction conditions are compatible with many functional groups, such as double and triple bonds, ketones, amides and amines, hydroxyl groups, carboxylic acids and carbamates. Mechanistic studies indicate the photooxidation of the arene followed by nucleophilic bromide addition as the likely pathway.

Advanced Synthesis & Catalysis published new progress about Aromatic hydrocarbons Role: RCT (Reactant), RACT (Reactant or Reagent). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Name: 4-Bromo-3-phenyl-1H-pyrazole.

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

Zhang, Dong; Gao, Di; Cai, Jinlin; Wu, Xiaoyu; Qin, Hong; Qiao, Kai; Liu, Chengkou; Fang, Zheng; Guo, Kai published the artcile< The ruthenium-catalyzed meta-selective C-H nitration of various azole ring-substituted arenes>, Computed Properties of 13788-92-6, the main research area is ruthenium catalyst meta selective nitration azole arene green chem.

The efficient ruthenium-catalyzed meta-selective CAr-H nitration of azole ring substituted arenes has been developed. In this work, Ru3(CO)12 was used as the catalyst, AgNO2 as the nitro source, HPcy3+·BF4- as the ligand, pivalic acid as the additive, and DCE as the solvent, and a wide spectrum of arenes bearing thiazole, pyrazolyl or removable oxazoline directing groups were tolerated in this meta-selective CAr-H nitration, affording the nitrated products in moderate to good yields. Moreover, this study reveals a gentler and environmentally friendly way to access meta-nitration arenes compared to the traditional process.

Organic & Biomolecular Chemistry published new progress about Azoles 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

Hudson, Liam; Mui, James; Vazquez, Santiago; Carvalho, Diana M.; Williams, Eleanor; Jones, Chris; Bullock, Alex N.; Hoelder, Swen published the artcile< Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept>, Formula: C10H17BN2O2, the main research area is quinazolinone synthesis antitumor SAR ALK2 cancer.

Structure-activity relationship and crystallog. data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chem. modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors.

Journal of Medicinal Chemistry published new progress about Activin receptor ACVRLK2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Formula: C10H17BN2O2.

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

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>, Formula: C15H19BN2O2, the main research area is imidazopyridazine inhibitor preparation antimalarial Plasmodium kinase inhibitor; Calcium-dependent protein kinase 1; Imidazopyridazine; Malaria; Plasmodium falciparum; SAR.

The structural diversity and SAR in a series of imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 has been explored and extended. The opportunity to further improve key ADME parameters by means of lowering log D was identified, and this was achieved by replacement of a six-membered (hetero)aromatic linker with a pyrazole. A short SAR study has delivered key examples with useful in vitro activity and ADME profiles, good selectivity against a human kinase panel and improved levels of lipophilic ligand efficiency. These new analogs thus provide a credible addnl. route to further development of the series.

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

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

Garcia da Silva, Artur Christian; Rodrigues, Bruna dos Santos; Andrade, Wanessa Machado; Marques dos Santos, Thais Rosa; de Carvalho, Flavio Silva; Sanz, German; Vaz, Boniek G.; Liao, Luciano M.; Menegatti, Ricardo; Valadares, Marize Campos published the artcile< Antiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells>, Computed Properties of 13788-92-6, the main research area is Nutlin analog antiangiogenic antitumoral agent melanoma cell; Antitumor drugs; Apoptosis; LQFM126; Melanoma; Molecular simplification; Nutlins.

Inhibition of mouse double minute 2 homolog (MDM2)-p53 interaction and reactivation of p53 signaling have been explored as effective anticancer therapeutic strategy. The potent and specific antitumor activity shown by Nutlins, first class of MDM2-p53 inhibitors discovered, has made these compounds potential antitumor candidates. To this end, we synthesized Nutlin-1 and Nutlin-2 analogs through mol. simplification and selected the compound with the most efficient antitumoral activity. Cytotoxicity of Nutlin-2 analog LQFM126 on B16F10 melanoma cells induced intense cytoplasmic vacuolization, reduction of cell size, chromatin condensation, cytoplasmic degeneration and nuclear fragmentation. LQFM126 antiproliferative effects mediated cell cycle retention in G0/G1 phase and increased the levels of cell cycle regulatory proteins p21 and p27. This Nutlin analog increased mitochondrial membrane potential, activated caspase-8, -9 and -3/7 and reduced VEGF levels in B16F10 cells. Therefore, LQFM126 promoted alterations suggestive of apoptosis, G0/G1 cell cycle arrest and suppression of angiogenesis through modulation of VEGF expression in B16F10 cells. Addnl., LQFM126 was classified as UN GHS category 4 (LD50 > 300-2000 mg/kg), suggesting it has low acute systemic toxicity. LQFM126 can be a promising prototype for anticancer therapy.

Chemico-Biological Interactions published new progress about Angiogenesis. 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

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