Month: October 2022

Link, Achim; Zhou, Yujing; Buchwald, Stephen L. published the artcile< CuH-Catalyzed Asymmetric Reductive Amidation of α,β-Unsaturated Carboxylic Acids>, Computed Properties of 374930-88-8, the main research area is chiral amide preparation enantioselective amidation carboxylic acid secondary amine.

The direct enantioselective copper hydride (CuH)-catalyzed synthesis of β-chiral amides from α,β-unsaturated carboxylic acids and secondary amines under mild reaction conditions is reported. The method utilizes readily accessible carboxylic acids and tolerates a variety of functional groups in the β-position including several heteroarenes. A subsequent iridium-catalyzed reduction to γ-chiral amines can be performed in the same flask without purification of the intermediate amides.

Organic Letters published new progress about Amidation (Reductive). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Computed Properties of 374930-88-8.

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

Sanchez-Arias, Juan A.; Rabal, Obdulia; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Ugarte, Ana; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer's Disease>, Formula: C13H19BrN4O2, the main research area is histone deacetylase phosphodiesterase 5 inhibitor preparation Alzheimer treatment; Alzheimer’s disease; HDACs; PDE5; dual inhibitor; tadalafil; vardenafil.

A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer’s disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead mol. CM-414 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, the authors have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead mol. bearing a different chemotype for in vivo testing.

ACS Chemical Neuroscience published new progress about Alzheimer disease. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

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

Phelan, James P.; Wiles, Rebecca J.; Lang, Simon B.; Kelly, Christopher B.; Molander, Gary A. published the artcile< Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies>, Application In Synthesis of 374930-88-8, the main research area is trifluoromethyl alkene preparation; silyl alc trifluoromethyl cross coupling palladium; Peterson elimination; organotrifluoroborate cross coupling palladium.

Two synergistic approaches to the facile assembly of complex α-trifluoromethyl alkenes are described. Using α-trifluoromethyl-β-silyl alcs. as masked trifluoromethyl alkenes, cross-coupling or related functionalization processes at distal electrophilic sites can be executed without inducing Peterson elimination. Subsequent Lewis acidic activation affords functionalized α-trifluoromethyl alkenes. Likewise, the development of a novel α-trifluoromethylvinyl trifluoroborate reagent complements this approach and allows a one-step cross-coupling of (hetero)aryl halides to access a broad array of complex α-trifluoromethyl alkenes.

Chemical Science published new progress about Addition reaction. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Application In Synthesis of 374930-88-8.

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

Wang, Junwei; Wang, Xuyan; Li, Hui; Ji, Dezhong; Li, Yuyan; Xu, Yungen; Zhu, Qihua published the artcile< Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors>, Safety of 1-Boc-4-(4-Formylphenyl)piperazine, the main research area is fluorobenzimidazolecarboxamide preparation PARP1 inhibitor anticancer potentiation; Antitumor; Benzimidazole; Fluorine atom; Inhibitors; PARP-1.

Novel 5-fluorobenzimidazole-4-carboxamides were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibitory activity. Compounds possessed high intrinsic PARP-1 inhibitory potency and were evaluated by in vitro cellular assays to measure their growth inhibitory activity as single agents against human colon cancer cell line HCT116 and their potentiation effect toward cytotoxic agent temozolomide (TMZ) against cancer cell line A549. One compound displayed strong inhibition against the PARP-1 enzyme with an IC50 of 43.7 nM, excellent cell inhibitory activity in HCT116 cells (IC50 = 7.4 μM) and potentiation of temozolomide cytotoxicity in cancer cell line A549 (PF50 = 1.6).

Bioorganic & Medicinal Chemistry Letters published new progress about Alveolar carcinoma. 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

Antonow, Dyeison; Kaliszczak, Maciej; Kang, Gyoung-Dong; Coffils, Marissa; Tiberghien, Arnaud C.; Cooper, Nectaroula; Barata, Teresa; Heidelberger, Sibylle; James, Colin H.; Zloh, Mire; Jenkins, Terence C.; Reszka, Anthony P.; Neidle, Stephen; Guichard, Sylvie M.; Jodrell, Duncan I.; Hartley, John A.; Howard, Philip W.; Thurston, David E. published the artcile< Structure-Activity Relationships of Monomeric C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Antitumor Agents>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is pyrrolobenzodiazepine aryl preparation antitumor structure activity relationship.

A comprehensive SAR investigation of the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer antitumor agents is reported, establishing the mol. requirements for optimal in vitro cytotoxicity and DNA-binding affinity. Both carbocyclic and heterocyclic C2-aryl substituents have been studied ranging from single aryl rings to fused ring systems, and also styryl substituents, establishing across a library of 80 analogs that C2-aryl and styryl substituents significantly enhance both DNA-binding affinity and in vitro cytotoxicity, with a correlation between the two. The optimal C2-grouping for both DNA-binding affinity and cytotoxicity was found to be the C2-quinolinyl moiety which, according to mol. modeling, is due to the overall fit of the mol. in the DNA minor groove, and potential specific contacts with functional groups in the floor and walls of the groove. This analog (I) was shown to delay tumor growth in a HCT-116 (bowel) human tumor xenograft model.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Tellis, John C.; Amani, Javad; Molander, Gary A. published the artcile< Single-Electron Transmetalation: Photoredox/Nickel Dual Catalytic Cross-Coupling of Secondary Alkyl β-Trifluoroboratoketones and -esters with Aryl Bromides>, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate, the main research area is secondary alkyltrifluoroborate aryl bromide cross coupling photoredox nickel catalyst; aralkyl ketone preparation; ester aralkyl preparation.

The first cross-coupling of secondary alkyl β-trifluoroboratoketones and -esters has been achieved through application of photoredox/nickel dual catalysis. Although the related β-trifluoroboratoamides have been effectively cross-coupled via Pd-catalysis, the corresponding ketones and esters had proven recalcitrant prior to this report. Reactions occur under mild conditions, and a variety of functional groups and sterically and electronically diverse reaction partners are tolerated.

Organic Letters published new progress about Aralkyl ketones Role: SPN (Synthetic Preparation), PREP (Preparation). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate.

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

Luesse, Sarah B.; Wells, Gregg; Miller, Jeanne; Bolstad, Erin; Bergmeier, Stephen C.; McMills, Mark C.; Priestley, Nigel D.; Wright, Dennis L. published the artcile< Synthesis of a functionalized oxabicyclo[2.2.1]heptene-based chemical library>, HPLC of Formula: 197638-83-8, the main research area is chem library oxabicycloheptane preparation antibacterial agent.

The 7-oxabicyclo[2.2.1]heptene ring system is a common structural motif in many pharmacol. interesting mols. The authors recognized the potential to employ this highly oxygenated and conformationally-restricted scaffold in diversity-oriented method to generate a library of non-chiral but topol. complex compounds and the synthesis of the target compounds was achieved by an acetalization cyclcocondensation of aldehydes with (exo,exo)-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol. Herein, the authors report the synthesis and biol. evaluation of two 96-member tricyclic library containing the oxabicyclo[2.2.1]heptene framework [6,9-epoxy-2,4-benzodioxepin derivatives, conformationally restricted acetals].

Combinatorial Chemistry & High Throughput Screening published new progress about Acetalization. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, HPLC of Formula: 197638-83-8.

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

Despras, Guillaume; Zamaleeva, Alsu I.; Dardevet, Lucie; Tisseyre, Celine; Magalhaes, Joao Gamelas; Garner, Charlotte; De Waard, Michel; Amigorena, Sebastian; Feltz, Anne; Mallet, Jean-Maurice; Collot, Mayeul published the artcile< H-Rubies, a new family of red emitting fluorescent pH sensors for living cells>, Product Details of C16H22N2O3, the main research area is H Rubies fluorescent hydrogen ion concentration sensor living cell.

Monitoring intracellular pH has drawn much attention due to its undeniably important function in cells. The widespread development of fluorescent imaging techniques makes pH sensitive fluorescent dyes valuable tools, especially red-emitting dyes which help to avoid the overcrowded green end of the spectral band. Herein, we present H-Rubies, a family of pH sensors based on a phenol moiety and a X-rhodamine fluorophore that display a bright red fluorescence upon acidification with pKa values spanning from 4 to 9. Slight structural modifications led to dramatic changes in their physicochem. properties and a relationship between their structures, their ability to form H-aggregates, and their apparent pKa was established. While mol. form H-Rubies can be used to monitor mitochondrial acidification of glioma cells, their functionalised forms were linked via click chem. to dextrans or microbeads containing a near IR Cy5 (Alexa-647) in order to provide ratiometric systems that were used to measure resp. the phagosomal and endosomal pH in macrophages (RAW 264.7 cells) using flow cytometry.

Chemical Science published new progress about Absorption spectra. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Product Details of C16H22N2O3.

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

Farmer, Luke A.; Wu, Zijun; Poon, Jia-Fei; Zilka, Omkar; Lorenz, Svenja M.; Huehn, Stephanie; Proneth, Bettina; Conrad, Marcus; Pratt, Derek A. published the artcile< Intrinsic and Extrinsic Limitations to the Design and Optimization of Inhibitors of Lipid Peroxidation and Associated Cell Death>, Reference of 229009-40-9, the main research area is lipid peroxidation inhibitor cell death RTA SAR metabolic stability.

The archetype inhibitors of ferroptosis, ferrostatin-1 and liproxstatin-1, were identified via high-throughput screening of compound libraries for cytoprotective activity. These compounds have been shown to inhibit ferroptosis by suppressing propagation of lipid peroxidation, the radical chain reaction that drives cell death. Herein, we present the first rational design and optimization of ferroptosis inhibitors targeting this mechanism of action. Engaging the most potent radical-trapping antioxidant (RTA) scaffold known (phenoxazine, PNX), and its less reactive chalcogen cousin (phenothiazine, PTZ), we explored structure-reactivity-potency relationships to elucidate the intrinsic and extrinsic limitations of this approach. The results delineate the roles of inherent RTA activity, H-bonding interactions with phospholipid headgroups, and lipid solubility in determining activity/potency. We show that modifications which increase inherent RTA activity beyond that of the parent compounds do not substantially improve RTA kinetics in phospholipids or potency in cells, while modifications that decrease intrinsic RTA activity lead to corresponding erosions to both. The apparent “”plateau”” of RTA activity in phospholipid bilayers (kinh ~2 x 105 M-1 s-1) and cell potency (EC50 ~4 nM) may be the result of diffusion-controlled reactivity between the RTA and lipid-peroxyl radicals and/or the potential limitations on RTA turnover/regeneration by endogenous reductants. The metabolic stability of selected derivatives was assessed to identify a candidate for in vivo experimentation as a proof-of-concept. This PNX-derivative demonstrated stability in mouse liver microsomes comparable to liproxstatin-1 and was successfully used to suppress acute renal failure in mice brought on by tissue-specific inactivation of the ferroptosis regulator GPX4.

Journal of the American Chemical Society published new progress about Antioxidants (radical-trapping antioxidant (RTA)). 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

Cui, Yi-Man; Li, Wei; Shen, Tian-Ze; Tao, Yong-Xing; Liu, Biao-Qi; Li, Xiao-Li; Zhang, Rui-Han; Jiang, De-Wei; Xiao, Wei-Lie published the artcile< Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors>, Category: piperazines, the main research area is antitumor biaryl pyridine breast cancer; biaryl pyridine preparation RSK kinase inhibitor mol docking; Breast Cancer; LJH685; RSK inhibitor; Structure-activity relationship; YB-1 phosphorylation.

In order to discover and develop new RSK kinase inhibitors, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of compound 3-pyridine derivative I to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among the synthesized compounds, after a preliminary screening, compound I showed good activity at inhibiting cell proliferation. Therefore, the authors took I as an example and performed mol. docking anal. on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound I has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound I is in line with the RSK inhibitor the authors designed and could be developed into a promising anti-tumor drug in the future.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Category: piperazines.

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