Category: 229009-40-9

Donnell, Andrew F.; Zhang, Yong; Stang, Erik M.; Wei, Donna D.; Tebben, Andrew J.; Perez, Heidi L.; Schroeder, Gretchen M.; Pan, Chin; Rao, Chetana; Borzilleri, Robert M.; Vite, Gregory D.; Gangwar, Sanjeev published the artcile< Macrocyclic pyrrolobenzodiazepine dimers as antibody-drug conjugate payloads>, Electric Literature of 229009-40-9, the main research area is macrocyclic pyrrolo benzodiazepine dimer preparation antibody drug conjugate mesothelin; Antibody-drug conjugates; Macrocycles; Pyrrolobenzodiazepines.

Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure-activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate.

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

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

Lee, Heajin; Liu, Wenjun; Brown, Adrienne S.; Landgraf, Ralf; Wilson, James N. published the artcile< Fluorescent Kinase Probes Enabling Identification and Dynamic Imaging of HER2(+) Cells>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is fluorescent kinase probe imaging HER2 cancer.

The human epidermal growth factor receptor, EGFR/ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small mol. kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. The authors report ERBB2 (also HER2) targeting kinase probes that exhibit a “”turn-on”” emission response upon binding. These live cell compatible probes differentiate ERBB2(+) cells from low-level, ERBB2(-) cells by targeting the intracellular ATP-binding pocket of ERBB2 with therapeutic inhibitor-like specificity. Beyond kinase expression levels, probe signal is linked to the phosphotyrosine-correlated activation state of the ERBB2 population. Addnl., the rapid signaling capability of the probes can report changes in activation state in live cells providing a unique type of complementary information to immunohistochem. assays of receptor kinase populations.

Analytical Chemistry (Washington, DC, United States) published new progress about Confocal laser scanning microscopy. 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

Lu, Xi; Wang, Xiao-Xu; Gong, Tian-Jun; Pi, Jing-Jing; He, Shi-Jiang; Fu, Yao published the artcile< Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters>, Formula: C11H17BN2O2, the main research area is functionalized geminal difluoroalkene preparation; haloalkene redox active ester defluorinative reductive coupling nickel catalyst.

An efficient method was developed for the synthesis of functionalized gem-difluoroalkenes I [R = c-hexyl, 4-BrC6H4(CH2)2, 4-CNC6H4O(CH2)2C(Me)2, etc.; Ar = 3,4-(OMe)2C6H3, 4-PhC6H4, 2-naphthyl, etc.] via nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with redox-active esters. The present reaction involved C(sp3)-F bond cleavage and C(sp3)-C(sp3) bond formation under very mild reaction conditions, while tolerating many sensitive functional groups and requiring minimal substrate protection. Therefore, this method provided an efficient and convenient approach for late-stage modification of biol. interesting mols.

Chemical Science published new progress about Carboxylic esters Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Formula: C11H17BN2O2.

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

Gazzard, Lewis; Williams, Karen; Chen, Huifen; Axford, Lorraine; Blackwood, Elizabeth; Burton, Brenda; Chapman, Kerry; Crackett, Peter; Drobnick, Joy; Ellwood, Charles; Epler, Jennifer; Flagella, Michael; Gancia, Emanuela; Gill, Matthew; Goodacre, Simon; Halladay, Jason; Hewitt, Joanne; Hunt, Hazel; Kintz, Samuel; Lyssikatos, Joseph; Macleod, Calum; Major, Sarah; Medard, Guillaume; Narukulla, Raman; Ramiscal, Judi; Schmidt, Stephen; Seward, Eileen; Wiesmann, Christian; Wu, Ping; Yee, Sharon; Yen, Ivana; Malek, Shiva published the artcile< Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is diazacarbazole preparation checkpoint kinase 1 inhibitor structure activity antitumor.

Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analog synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.

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

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

Vitorino, Philip; Yeung, Stacey; Crow, Ailey; Bakke, Jesse; Smyczek, Tanya; West, Kristina; McNamara, Erin; Eastham-Anderson, Jeffrey; Gould, Stephen; Harris, Seth F.; Ndubaku, Chudi; Ye, Weilan published the artcile< MAP4K4 regulates integrin-FERM binding to control endothelial cell motility>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is MAP4K4 moesin talin beta1 integrin vascular endothelial cell migration; angiogenesis inhibitor synthesis MAP4K4 signaling plasma membrane retraction HUVEC.

Cell migration is a stepwise process that coordinates multiple mol. machineries. Using in vitro angiogenesis screens with short interfering RNA and chem. inhibitors, we define here a MAP4K4-moesin-talin-β1-integrin mol. pathway that promotes efficient plasma membrane retraction during endothelial cell migration. Loss of MAP4K4 decreased membrane dynamics, slowed endothelial cell migration, and impaired angiogenesis in vitro and in vivo. In migrating endothelial cells, MAP4K4 phosphorylates moesin in retracting membranes at sites of focal adhesion disassembly. Epistasis analyses indicated that moesin functions downstream of MAP4K4 to inactivate integrin by competing with talin for binding to β1-integrin intracellular domain. Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells. Addnl., α5β1-integrin blockade reversed the membrane retraction defects associated with loss of Map4k4 in vitro and in vivo. Our study uncovers a novel aspect of endothelial cell migration. Finally, loss of MAP4K4 function suppressed pathol. angiogenesis in disease models, identifying MAP4K4 as a potential therapeutic target.

Nature (London, United Kingdom) published new progress about Angiogenesis. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Holmes, Jane L.; Almeida, Lynsie; Barlaam, Bernard; Croft, Rosemary A.; Dishington, Allan P.; Gingipalli, Laksmaiah; Hassall, Lorraine A.; Hawkins, Janet L.; Ioannidis, Stephanos; Johannes, Jeffrey W.; McGuire, Thomas M.; Moore, Jane E.; Patel, Anil; Pike, Kurt G.; Pontz, Timothy; Wu, Xiaoyun; Wang, Tao; Zhang, Hai-Jun; Zheng, Xiaolan published the artcile< Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is fused heterocycle preparation.

Examples of hydroxymethylated analogs of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones were sparse or non-existent in the scientific literature. Synthesis of such compounds by using standard procedures from readily available raw materials was demonstrated.

Synthesis published new progress about Aryl aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

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

Zhen, Shijie; Yi, Xiaoqing; Zhao, Zujin; Lou, Xiaoding; Xia, Fan; Tang, Ben Zhong published the artcile< Drug delivery micelles with efficient near-infrared photosensitizer for combined image-guided photodynamic therapy and chemotherapy of drug-resistant cancer>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is near IR photosensitizer guided photodynamic antitumor reduction release micelle; Chemotherapy; Drug delivery; Near-infrared fluorophore; Photodynamic therapy; Photosensitizer.

The combination of photodynamic therapy (PDT) and chemotherapy (CT) offers a promising approach for the tumor eradication for overcoming multidrug resistance (MDR), which is a major obstacle to effective cancer treatment. However, for PDT, simultaneously achieving near-IR (NIR) emission and efficient reactive oxygen species (ROS) generation with low dark toxicity is urgently needed but remains challenging. Herein, a series of novel fluorophores with strong NIR emission, hybridized local and charge transfer characteristics, good two-photon absorption, high photostability, low dark cytotoxicity and excellent ROS generation ability are developed. By encapsulating the NIR fluorophore (DEB-BDTO) as a photosensitizer along with a drug resistance inhibitor tariquidar (TQR) within a polymeric prodrug (PMP), a reduction-sensitive drug co-delivery system (DEB/TQR@PMP micelles) is constructed. The DEB/TQR@PMP micelles exhibit a prominent synergistic lethal effect of PDT and CT on SKOV-3 cells and SKOV-3/MDR cells, and can apparently enhance the inhibition of tumor growth compared with sole PDT or CT in the tumor-bearing mouse model. Both in vitro and in vivo experiments prove that the new NIR fluorophores are excellent photosensitizers and can furnish an efficient combination therapy of image-guided PDT and CT within drug delivery micelles, which is particularly useful for eradicating multidrug resistance cancer.

Biomaterials 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