Month: October 2022

Jung, Woo-Ok; Mai, Binh Khanh; Spinello, Brian J.; Dubey, Zachary J.; Kim, Seung Wook; Stivala, Craig E.; Zbieg, Jason R.; Liu, Peng; Krische, Michael J. published the artcile< Enantioselective Iridium-Catalyzed Allylation of Nitroalkanes: Entry to β-Stereogenic α-Quaternary Primary Amines>, Product Details of C13H19BrN4O2, the main research area is homoallylic nitroalkane preparation enantioselective; nitroalkane allylic acetate allylation iridium catalyst.

The first systematic study of simple nitronate nucleophiles in iridium-catalyzed allylic alkylation was described. Using a tol-BINAP-modified π-allyliridium C,O-benzoate catalyst, α,α-disubstituted nitronates substitute racemic branched alkyl-substituted allylic acetates, thus providing homoallylic nitroalkanes. DFT calculations revealed early transition states that render the reaction less sensitive to steric effects and distinct trans-effects of diastereomeric chiral-at-iridium π-allyl complexes that facilitate formation of congested tertiary-quaternary C-C bonds.

Journal of the American Chemical Society published new progress about Alkanes, nitro Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Product Details of C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Matos, Ana M.; Man, Teresa; Idrissi, Imane; Souza, Cleide C.; Mead, Emma; Dunbar, Charlotte; Wolak, Joanna; Oliveira, Maria C.; Evans, David; Grayson, James; Partridge, Benjamin; Garwood, Claire; Ning, Ke; Sharman, Gary; Chen, Beining; Rauter, Amelia P. published the artcile< Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer's disease: synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions>, Category: piperazines, the main research area is methylpiperazinyl flavone amyloid beta oligomer cellular prion protein.

With no currently available disease-modifying drugs, Alzheimer’s disease is the most common type of dementia affecting over 47 million people worldwide. In light of the most recent discoveries placing the cellular prion protein (PrPC) as a key player in amyloid βoligomer (Aβo)-induced neurodegeneration, we investigated whether the neuroprotective potential of nature-inspired flavonoids against Aβo-promoted toxicity would translate into the ability to disrupt PrPC-Aβo interactions. Hence, we synthesized a small library of flavones and studied their binding affinity towards Aβo by STD-NMR. C-glucosyl flavones exhibited improved binding affinity with morpholine, thiomorpholine or N-methylpiperazine rings attached to the flavone skeleton in ring B para position. Moreover, a N-methylpiperazinyl flavone displayed suitable physicochem. properties and optimal water solubility even without the sugar moiety, and a high interaction with Aβo involving the whole flavone core. Its C-glucosyl derivative, was, however, the best compound to inhibit PrPC-Aβo interactions in a dose-dependent manner, with 41% of inhibition capacity at 10μM. The potential of C-glucosyl flavones and their aglycons as protein-protein interaction inhibitors able to tackle PrPC-Aβo interactions is here presented for the first time, and supports this class of compounds as new prototypes for further development in the treatment of Alzheimer’s disease.

Pure and Applied Chemistry published new progress about Aglycons Role: BSU (Biological Study, Unclassified), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Category: piperazines.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Li, Jing; Tan, Guishan; Cai, Yabo; Liu, Ruihuan; Xiong, Xiaolin; Gu, Baohua; He, Wei; Liu, Bing; Ren, Qingyun; Wu, Jianping; Chi, Bo; Zhang, Hang; Zhao, Yanzhong; Xu, Yangrui; Zou, Zhenxing; Kang, Fenghua; Xu, Kangping published the artcile< A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET>, Reference of 229009-40-9, the main research area is human renal cell carcinoma apigenin derivative MET; Apigenin derivatives; Drug-resistant MET mutations; MET; MET downstream signaling; Renal cell carcinoma.

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about Apoptosis. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Reference of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Yang, Xiaoguang; Zhou, Yibo; Zhang, Xiufang; Yang, Sheng; Chen, Yun; Guo, Jingru; Li, Xiaoxuan; Qing, Zhihe; Yang, Ronghua published the artcile< A TP-FRET-based two-photon fluorescent probe for ratiometric visualization of endogenous sulfur dioxide derivatives in mitochondria of living cells and tissues>, Computed Properties of 197638-83-8, the main research area is sulfur dioxide fluorescence probe two photon FRET.

A ratiometric two-photon fluorescent probe for SO2 derivatives was first proposed based on acedan-merocyanine dyads (I) via a TP-FRET strategy. It was successfully applied to visualization of the fluctuations of enzymically generated SO2 derivatives in the mitochondria of HepG2 cells and rat liver tissues using two-photon fluorescence microscopy imaging.

Chemical Communications (Cambridge, United Kingdom) published new progress about Fluorescence imaging. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Computed Properties of 197638-83-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Jouffroy, Matthieu; Kelly, Christopher B.; Molander, Gary A. published the artcile< Thioetherification via Photoredox/Nickel Dual Catalysis>, Related Products of 374930-88-8, the main research area is thioether aryl heteroaryl preparation; aryl heteroaryl bromide thioetherification thiol hypervalent alkylsilicate nickel photoredox.

Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols are described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated.

Organic Letters published new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Related Products of 374930-88-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Hieke, Martina; Roedl, Carmen B.; Wisniewska, Joanna M.; Buscato, Estella; Stark, Holger; Schubert-Zsilavecz, Manfred; Steinhilber, Dieter; Hofmann, Bettina; Proschak, Ewgenij published the artcile< SAR-study on a new class of imidazo[1,2-a]pyridine-based inhibitors of 5-lipoxygenase>, Safety of 1-Boc-4-(4-Formylphenyl)piperazine, the main research area is imidazopyridinamine cyclohexyl morpholinophenyl preparation lipoxygenase inhibitor.

A novel class of 5-lipoxygenase (5-LO) inhibitors characterized by a central imidazo[1,2-a]pyridine scaffold, a cyclohexyl moiety and an aromatic system, is presented. This scaffold was identified in a virtual screening study and exhibits promising inhibitory potential on the 5-LO. The structure-activity relationships of this compound class was investigated. N-Cyclohexyl-6-methyl-2-(4-morpholinophenyl)imidazo[1,2-a]pyridine-3-amine was identified as a potent 5-LO inhibitor [IC50 = 0.16 μM (intact cells) and 0.1 μM (cell-free)], which may possess potential as an effective lead compound intervening with inflammatory diseases and certain types of cancer.

Bioorganic & Medicinal Chemistry Letters published new progress about 197638-83-8. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Safety of 1-Boc-4-(4-Formylphenyl)piperazine.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Henning, Nathaniel J.; Boike, Lydia; Spradlin, Jessica N.; Ward, Carl C.; Liu, Gang; Zhang, Erika; Belcher, Bridget P.; Brittain, Scott M.; Hesse, Matthew J.; Dovala, Dustin; McGregor, Lynn M.; Valdez Misiolek, Rachel; Plasschaert, Lindsey W.; Rowlands, David J.; Wang, Feng; Frank, Andreas O.; Fuller, Daniel; Estes, Abigail R.; Randal, Katelyn L.; Panidapu, Anoohya; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Nomura, Daniel K. published the artcile< Deubiquitinase-targeting chimeras for targeted protein stabilization>, Reference of 22476-74-0, the main research area is cystic fibrosis deubiquitinase chimera protein stabilization.

Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). Here we present deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small mols. consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS. [graphic not available: see fulltext]

Nature Chemical Biology published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Yang, Wei; Liu, Xiaolong; Song, Chunli; Ji, Sen; Yang, Jianhong; Liu, Yang; You, Jing; Zhang, Jie; Huang, Shenzhen; Cheng, Wei; Shao, Zhenhua; Li, Linli; Yang, Shengyong published the artcile< Structure-activity relationship studies of phenothiazine derivatives as a new class of ferroptosis inhibitors together with the therapeutic effect in an ischemic stroke model>, SDS of cas: 229009-40-9, the main research area is SAR preparation phenothiazine derivative ferroptosis ischemic stroke BBB; Ferroptosis inhibitor; Ischemic stroke; Promethazine derivatives; Structure-activity relationship.

Ferroptosis is a new type of programmed cell death discovered recently and has been demonstrated to be involved in a number of human diseases such as ischemic stroke. Ferroptosis inhibitors are expected to have potential to treat these diseases. Herein, we report the identification of promethazine derivatives as a new type of ferroptosis inhibitors. Structure-activity relationship (SAR) analyses led to the discovery of the most potent compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (51), which showed an EC50 (half maximal effective concentration) value of 0.0005μM in the erastin-induced HT1080 cell ferroptosis model. In the MCAO (middle cerebral artery occlusion) ischemic stroke model, 51 presented an excellent therapeutic effect. This compound also displayed favorable pharmacokinetic properties, in particular, a good ability to permeate the blood-brain barrier. Overall, 51 could be a promising lead compound for the treatment of ferroptosis related diseases and deserves further investigations.

European Journal of Medicinal Chemistry published new progress about Blood-brain barrier (permeation). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, SDS of cas: 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

De Savi, Chris; Waterson, David; Pape, Andrew; Lamont, Scott; Hadley, Elma; Mills, Mark; Page, Ken M.; Bowyer, Jonathan; Maciewicz, Rose A. published the artcile< Hydantoin based inhibitors of MMP13-Discovery of AZD6605>, Product Details of C13H19BrN4O2, the main research area is piperidine ether aryl piperazine hydantoin inhibitor MMP13 osteoarthritis; Cyp P450; Hydantoin; Lead optimisation; MMP13; Zinc binder.

Piperidine ether and aryl piperazine hydantoins are reported as potent inhibitors of MMP13. A medicinal chem. campaign focused on replacing the reverse hydroxamate zinc binding group associated with historical inhibitors with a hydantoin zinc binding group then optimizing MMP13 potency, solubility and DMPK properties while maintaining good selectivity over MMP14. A number of high quality candidates were progressed and following rat and dog safety evaluation, AZD6605 (3m) was identified as a candidate drug.

Bioorganic & Medicinal Chemistry Letters published new progress about Enzyme inhibitors. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Product Details of C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics